EP4200546A1

EP4200546A1 - Valve block for a one-time use in a bio process

Info

Publication number: EP4200546A1
Application number: EP21765892.1A
Authority: EP
Inventors: Christian Grimm
Original assignee: Sartorius Stedim Biotech GmbH
Current assignee: Sartorius Stedim Biotech GmbH
Priority date: 2020-08-18
Filing date: 2021-08-18
Publication date: 2023-06-28
Also published as: DE202020104788U1; WO2022038189A1; US20230272865A1; US12140235B2

Abstract

The invention relates to a valve block (10) for a one-time use in a bio process, comprising multiple valve units (12). The valve block (10) has a single-piece block body (14) with a main channel (16), at least one auxiliary channel (18) per valve unit (12), a valve seat (22) between the auxiliary channel (18) and the main channel (16), a closure part (24) with a gripping section (32), and an actuator (36) that is coupled to the gripping section (32) of the closure part (24) and can move the closure part (24) out of a first switch position of the valve unit (12), in which the closure part (24) is pressed against the valve seat (22) and a fluidic connection between the auxiliary channel (18) and the main channel (16) is blocked, and into a second switch position of the valve unit (12), in which the closure part (24) is lifted from the valve seat (22) and the fluid connection between the auxiliary channel (18) and the main channel (16) is released. The gripping section (32) is arranged such that the gripping section is sealed off from the main channel (16) as well as from the auxiliary channel (18) in the two switch positions of the valve unit (12).

Description

Valve block for single use in a bioprocess

The invention relates to a valve block for single use in a bioprocess.

The trends of recent years in the biopharmaceutical industry are increasingly pointing in the direction of the use of single-use components, in particular due to the high flexibility and savings in time, investment and operating expenses such as cleaning and their validation and verification. Disposable components are no longer only used in the area of product and process development, but now also in the area of clinical trial manufacturing (abbr.: CTM) for the approval process and even in commercial "good manufacturing practice" ( English: Good Manufacturing Practice, abbreviation: GMP) in the production of pharmaceuticals.

Disposable components are clearly distinguished in the professional world from conventional reusable components (English: reusable, multi-use), e.g. B. stainless steel tanks, which are not simply disposed of after a single use, but have to be cleaned, sterilized and tested again for each further use. Disposable systems are desired not only for small-volume processes, but also for larger scale, whereby the costs for such systems should not become unrealistically high.

An example of a process step relevant in the biopharmaceutical industry is chromatographic purification. Various types of chromatography methods, such as affinity chromatography (e.g. with protein) or ion-exchange chromatography (abbr. IEX), in particular cation exchange chromatography (CEX) or anion exchange chromatography (abbr. : AEX) to use that can be realized both with classic separation columns and with membrane adsorbers. Depending on the type, the process can be run in either bind-and-elute or flow-through mode.

In addition to process pressure and media flow, important parameters for controlling these process steps are the composition and properties of the various buffers and rinsing solutions. In order to control the addition and processing of the different buffers, the addition, the sequence and the flow rates of the individual buffers and rinsing solutions must be controllable. In most cases, this is implemented using a pump in combination with a series of control or pinch valves. When using disposable components, this can be done either via so-called hose pinch valves or via diaphragm control valves. Arrangements made up of several hose pinch valves or diaphragm control valves have a number of disadvantages, some of which are briefly explained below.

- A large "footprint", i. H. the hose assemblies are very large and unwieldy and take up a lot of space on the respective device or process system.

- A large dead space in the hoses and possibly other components, i. H. there is still a relatively large amount of medium in the tube system after the end of the process step, which is flushed out unused. This is uneconomical since the medium often has a high financial value (e.g. antibody material). Due to the large dead space, there are also unwanted dilution and mixing effects during the process and thus possibly a broadening of the chromatogram peaks and, as a result, an inefficient separation.

- A large number of hose-valve connections, which entails an increased risk of leaks and leaks, as well as a relatively complex type of assembly with a consequent increased production effort. - Possibly negative properties on the target molecule of the process, ie it could be damaged by the aerodynamically unfavorable geometry of the components and the associated undesirable pressure drops.

The object of the invention is to avoid or compensate for the disadvantages mentioned above and to create an inexpensive, compact and easy-to-handle alternative for disposable applications.

This object is achieved by a valve block having the features of claim 1. Advantageous and expedient configurations of the valve block according to the invention are specified in the dependent claims.

The valve block according to the invention is intended for single use in a bioprocess and comprises a number of valve units. The valve block includes a one-piece block body with a main passage formed therein. Furthermore, the valve block comprises, per valve unit, at least one sub-channel formed in the block body, a valve seat formed in the block body between the sub-channel and the main channel, and a closing part with a gripping section. In addition, the valve block includes an actuator for each valve unit, which is coupled to the gripping section of the closure part and moves the closure part from a first switching position of the valve unit, in which the closure part is pressed against the valve seat and blocks a flow connection between the secondary channel and the main channel, into a second Can transfer switching position of the valve unit, in which the closure part is lifted from the valve seat and the flow connection between the secondary channel and the main channel releases. The gripping section of the closure part is arranged in such a way that it is sealed against both the main channel and the secondary channel in both switching positions of the valve unit.

The invention is based on the finding that the large number of tube connections and the associated dead volume of known addition arrangements, which are intended for single use in a bioprocess, can be avoided by jointly forming a plurality of one-way valve units in a valve block. The valve block according to the invention allows an extremely compact, space-saving arrangement of the valve units with minimal dead space. Thanks to those formed directly in the block body of the valve block channels, fewer hoses and fewer hose connections are required, which makes handling much easier and also minimizes the risk of incorrect assembly.

Another essential advantage of the valve block according to the invention is that the actuators are completely separated from the medium flowing through the channels of the valve block. This is made possible by the gripping section of the closure part, to which the actuator is coupled, being arranged in an area which is sealed off from the channels in both switch positions of the valve unit. Thanks to this separation, it is not absolutely necessary to sterilize the actuators, since they do not come into contact with the medium and therefore cannot contaminate the medium.

In this context, a stable but solvable, i. H. a storage of the actuators on the block body that can be separated easily and without damage or even destruction is advantageous, so that after the valve block has been used once, the actuators do not have to be disposed of together with the remaining components of the valve block, but can be reused. The actuators are preferably mounted on the block body with the aid of valve caps, which can also assume additional functions, in particular closing the block body after the assembly of the valve unit components arranged therein.

So that the actuators can be removed from the block body without any problems, it should also be possible to detach the coupling of the actuators to the gripping sections of the closure part.

The design of the valve block according to the invention enables the range of applications to be expanded and operational safety to be increased, in particular with regard to applications with high pressures. Applications with pressures of 4 bar and more are planned with the valve block according to the invention. This is hardly possible with conventional, non-reinforced hose lines, but it is possible with a block body made of a resistant, hard plastic in which the channels can withstand such pressures.

Preferably, the valve seat of each valve unit is at least partially substantially funnel-shaped and the closure member has a skirt portion on, which is adapted to the funnel shape of the valve seat. A substantially conical jacket section is particularly suitable for this purpose. The funnel shape of the valve seat proves to be advantageous in terms of flow technology and with regard to the forces required to close the valve seat, particularly in the case of a secondary channel arranged transversely and at the same time offset in height to the main channel. Due to the lower force required to close the valve compared to other approaches, smaller electric motor, pneumatic or magnetic drives can be used for the actuators.

According to a particular embodiment of the invention, an edge area of the closure part is fixed to the block body, and at least the casing section of the closure part is formed from an elastically deformable material. In this embodiment, the gripping section of the closure part is also coupled to the skirt section. By clamping the closure part is fixed in a predetermined position; nevertheless, the elastically deformable casing section can be raised and lowered from the valve seat by the actuator via the gripping section in order to release or block the flow connection between the secondary channel and the main channel. The advantage here is that the closure part can be clamped precisely and the movement or deformation of the closure part to change the switching position takes place exclusively inside the block body.

To fix the closure part, the edge area of the closure part can be clamped between a valve cap and a shoulder of the block body. The necessary attachment of the valve cap to the block body can in turn be achieved by welding, gluing, a snap-in connection or another suitable technique.

In a preferred embodiment of the invention, the jacket section of the closure part merges into a base that faces the main channel or the secondary channel. The gripping section extends from the bottom into a cavity of the closure part surrounded by the jacket section. Such a geometry enables the valve seat to be released and locked easily and effectively, in each case without great effort. In order to raise and lower the closure part, the actuator preferably has a deflectable gripper which is coupled to the gripping section of the closure part.

A particular development of the invention provides that the jacket section of the closure part has an expandable and compressible structure. The stretchable and compressible structure may resemble that of a bellows or accordion with pleats, or it may meander or have a similar shape. Such a structure permits or supports the elastic deformation of the skirt portion required for the raising and lowering of the skirt portion of the restrained closure member.

The function of the valve units is not limited to blocking and releasing a flow connection between a secondary channel and the main channel. At least in one of the valve units it can be provided that the closure part can block or open a side channel independently of the main channel and/or can open or block one or more branches of a side channel.

With regard to efficient production and assembly, it is advantageous for at least some of the closure parts of the valve units to be designed in one piece with one another. The same applies to the valve caps of the valve units.

The manufacture and assembly of the valve block can be further simplified in that connection pieces are formed in one piece with the block body at the ends of the main duct and the secondary ducts that lead out of the block body.

The design of the valve block according to the invention allows all the components of the valve block, with the exception of the actuators, to be pre-sterilized and possibly also pre-assembled.

The actuators of the valve block can be controlled flexibly. In particular, the actuators are designed in such a way that they can be controlled individually, in groups or all together by a control unit. It is thus possible to actuate the valve units of the valve block individually, in groups or all at the same time. The transfer of the closing part of the valve unit from the first to the second switch position and vice versa can also take place quasi-continuously when using a suitable actuator drive in order to enable a certain flow control through the flow connection between the main channel and the secondary channel.

Further features and advantages of the invention emerge from the following description and from the accompanying drawings, to which reference is made. In the drawings show:

- Figure 1 is a perspective view of a valve block according to the invention;

FIG. 2 shows a cross-sectional view of the valve block from FIG. 1; and

- Figure 3 is a longitudinal sectional view of the valve block of Figure 1.

A valve block 10 for use in a bioprocess is shown in FIGS. In the embodiment shown, three valve units 12 are combined in the valve block 10, but there can also be fewer or more (eg twelve). The basic structure of the valve block 10 is explained in more detail below, regardless of the number of valve units 12 .

In an elongate block body 14, which is essentially cuboid here, of the valve block 10, a main duct 16 running in its longitudinal direction x and a plurality of secondary ducts 18, each assigned to a valve unit 12, are formed, which in the y-direction are transverse to the main duct 16 and above it with respect to the z-direction of the main channel 16 run. The secondary channels 18 can each extend from the respective valve unit 12 to only one longitudinal side (as shown here) or to two or even three longitudinal sides of the block body 14 . In general, the courses and the number of branches of the secondary channels 18 can be configured in the block body 14 in accordance with the requirements of the respective application as desired. Basically it is also possible to provide a branched main channel 16 or several main channels 16 in the block body 14 .

At the ends of the main duct 16 and the secondary ducts 18 leading out of the block body 14 there are provided connecting pieces 20 to which hose lines can be connected. The connectors 20 can Hose barbs or sub-components for making a tri-clamp or luer-lock connection or another suitable type of connection. Typical sizes for the inside diameter of fittings 20 and main passage 16 and branch passages 18 are 1/8" (3.18 mm), 1/4" (6.35 mm), 3/8" (9.53 mm), 1/2” (1.27cm), 3/4” (1.91cm) and 1” (2.54cm). Connectors 20 that are not required can be sealed with blind plugs.

The block body 14, preferably together with the fittings 20, is formed in one piece from a durable, hard plastic. That is, the block body 14 is preferably, but not necessarily, made from a single and unitary piece. If the block body 14 is not made from a single and unitary piece, its sections are not only solid, but so intimately connected that they do not appear as several components joined together and in any case can no longer be detached from one another without being destroyed will. Additional components can be welded or glued to the block body 14 . The material for the block body 14 is z. B. polyolefins such as polyethylene (PE) and polypropylene (PP), or polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT) or polycarbonates (PC).

The secondary channels 18 are each in flow communication with the main channel 16, and these flow connections can be released individually, in groups or together with the aid of the valve units 12, as will be explained later.

In the area of the flow connection between the associated secondary channel 18 and the main channel 16, each valve unit 12 has a valve seat 22 formed by a material recess in the block body 14. In the exemplary embodiment shown, the valve seats 22 are essentially funnel-shaped.

A closure part 24 is seated on each of the valve seats 22 and is formed from an elastically deformable material such as rubber, silicone, thermoplastic elastomer (TPE), thermoplastic polyurethane (TPU) or a similar material. The closure part 24 can be produced in particular by injection molding or an additive manufacturing process (e.g. 3D printing). The outer contour of the closure part 24 is adapted to the flat shape of the valve seat 22 in such a way that it can close the flow connection between the secondary channel 18 and the main channel 16 . Depending on the design and arrangement of the secondary ducts 18, a closure part 24 of a valve unit 12 can also be used to block only one secondary duct 18 (i.e. without affecting the main duct 16), e.g. if the secondary duct 18 extends between opposite sides of the block body 14. If the side channel has 18 branches, only one or more of these branches can be blocked with the closure part 24 . In principle, combinations of the possibilities described above can also be implemented, e.g. blocking the flow connection between the main channel 16 and one or more branches of a secondary channel 18. For the sake of simplicity, however, with regard to the function of the valve units 12, only those shown in particular in Figures 2 and 3 shown variant, in which the closure part 24 can release or close the flow connection between an associated secondary channel 18 and the main channel 16.

The closure part 24 is hollow on the inside and has a bottom 26 which faces the main channel 16 . The base 26 is adjoined by a substantially conical casing section 30 that runs around in relation to the z-direction and laterally surrounds the cavity 28 of the closure part 24 and adjoins the inner end of the secondary channel 18 . The cavity 28 is open in the z-direction.

The jacket section 30 of the closure part 24 has a bellows, accordion, meander or comparable structure that can be stretched and compressed—not shown in detail in the figures—the importance of which will be explained in more detail later.

The closure member 24 also includes a gripping portion 32 that extends from the bottom 26 of the closure member 24 into the cavity 28 . The gripping section 32 has a convex shape here, although this is not absolutely necessary. It should be noted that the gripping portion 32 is in an area of the valve block 10 that is permanently sealed to both the main passage 16 and the branch passage 18 .

The closure parts 24 of the individual valve units 12 can also be connected to one another, e.g. B. at the top of the shell sections 30. Characterized manufacture is simplified since several or all closure parts 24 can be manufactured and assembled together as a unit.

The closure parts 24 are held in position in the block body 14 by valve caps 34 . The valve caps 34 are attached to the upper side of the block body 14--in the z-direction--and each clamp a laterally outwardly projecting edge region of the jacket sections 30 of the closure parts 24 on a shoulder of the block body 14. The valve caps 34 themselves are fastened by welding, gluing, clamping, a snap-in connection or some other suitable connection technique.

In principle, it is possible to form the valve caps 34 in one piece with one another, i. H. the valve caps 34 are joined together and can be manufactured together as a unit.

The valve caps 34 also each provide stable mounting for an actuator 36 (drive unit) for actuating the respective valve unit 12 . The storage is detachable, i. H. the actuators 36 can be disassembled from the valve block 10 after it has been used.

The type of drive of the actuator 36 (electrical, pneumatic, hydraulic, etc.) is not important here, but rather the mechanical actuation of the respective valve unit 12 carried out by the actuator 36, which is explained below.

The actuator 36 has a gripper 38 that can move linearly in the z-direction. The gripper 38 extends through the valve cap 34 into the cavity 28 and grips the gripping portion 32, although other types of coupling are possible. In either case, the coupling is releasable so that the entire actuator 36, including the gripper 38, can be removed from the valve cap 34 and block body 14.

At least two switching positions can be implemented in each valve unit 12 by means of the associated actuator 36 . The first switching position is shown in FIGS. The gripper 38 presses the closure part 24 against the valve seat 22, so that the flow connection between the main channel 16 and the secondary channel 18 of the valve unit 12 is blocked. In the second switching position, the gripper 38 pulls the gripping section 32 with the base 26 of the closure part 24 upwards in the z-direction. Since the upper edge portion of the skirt portion 30 is supported by the valve cap 34, the skirt portion 30 deforms elastically. This is made possible or at least promoted by the stretchable and compressible structure of the jacket section 30 explained above. In the second switching position, the lower part of the closure part 24 is raised so far in the z-direction that a flow connection is established between the main channel 16 and the secondary channel 18 of the valve unit 12 . This flow connection is sufficient to bring about a desired flow from the main channel 16 into the secondary channel 18 or vice versa (depending on the application).

In principle, it is also possible to provide further intermediate positions by appropriately controlling the actuator 36 in order to adjust the flow to a desired level. A quasi-continuous adjustment of the flow as required is preferred.

All components of the valve block 10, with the exception of the actuators 36, are designed as dedicated disposable components and can be preassembled and sterilized before use - or even before delivery - in particular by gamma radiation. In this case, the materials of the individual valve block components are selected in such a way that their mechanical properties are not significantly impaired by the radiation with regard to their function. Before the valve block 10 is put into operation, only the actuators 36 have to be mounted and their grippers 38 coupled to the gripping sections 32 of the closure parts and the hose connections made. Since, regardless of the switching positions of the valve units 12, neither the grippers 38 nor other parts of the actuators 36 come into contact with the medium flowing through the main channel 16 and the secondary channels 18, the actuators 36 do not necessarily have to be sterilized.

During operation, the valve units 12 of the valve block 10 can be controlled individually, in groups or all together via the actuators 36 in order to release the supply of buffer, rinsing medium, etc. through the secondary channels 18 into the main channel 16 in a bioprocess or to transfer a medium from the main channel 16 on to distribute the side channels 18. Of course, the valve block 10 is not limited to these applications.

After the valve block 10 has been used once in the bioprocess, the actuators 36 are removed and the remaining components of the valve block 10 can be disposed of as a unit, possibly also together with the connected hose lines.

Reference character height

10 valve block

12 valve unit

14 block body 16 main channel

18 secondary channel

20 fitting

22 valve seat

24 locking part 26 bottom

28 cavity

30 coat section

32 gripping section

34 valve cap 36 actuator

38 grippers

Claims

patent claims

1. Valve block (10) for single use in a bioprocess, with a plurality of valve units (12), the valve block (10) comprising a one-piece block body (14) with a main channel (16) formed therein, and for each valve unit (12)

- at least one secondary channel (18) formed in the block body (14),

- A valve seat (22) formed in the block body (14) between the secondary channel (18) and the main channel (16).

- a closure part (24) with a gripping section (32),

- an actuator (36), which is coupled to the gripping section (32) of the closure part (24) and the closure part (24) from a first switching position of the valve unit (12), in which the closure part (24) against the valve seat (22) is pressed and blocks a flow connection between the secondary channel (18) and the main channel (16), can be converted into a second switching position of the valve unit (12), in which the closure part (24) is lifted from the valve seat (22) and the flow connection between the releases the secondary channel (18) and the main channel (16), the gripping section (32) of the closure part (24) being arranged in such a way that in both switch positions of the valve unit (12) it acts against both the main channel (16) and against the secondary channel ( 18) is sealed.

2. Valve block (10) according to claim 1, characterized in that the actuator (36) is mounted stably but releasably on the block body (14), preferably with the aid of a valve cap (34).

3. Valve block (10) according to claim 2, characterized in that the coupling of the actuator (36) to the gripping section (32) of the closure part (24) is detachable.

4. Valve block (10) according to any one of the preceding claims, characterized in that the block body (14) is formed from a durable, hard plastic.

5. Valve block (10) according to one of the preceding claims, characterized in that the valve seat (22) is at least partially essentially funnel-shaped and the closure part (24) has a jacket section (30) adapted to the funnel shape of the valve seat (22), which is preferably substantially conical.

6. Valve block (10) according to Claim 5, characterized in that an edge region of the closure part (24) is fixed to the block body (14) and at least the jacket section (30) of the closure part (24) is formed from an elastically deformable material, the Gripping portion (32) of the closure member (24) is coupled to the skirt portion (30).

7. Valve block (10) according to claim 6, characterized in that for fixing the closure part (24) the edge region of the closure part (24) is clamped between a valve cap (34) and a shoulder of the block body (14).

8. Valve block (10) according to claim 6 or 7, characterized in that the jacket section (30) of the closure part (24) merges into a base (26) which faces the main channel (16) or the secondary channel (18) and from in which the gripping section (32) extends into a cavity (28) of the closure part (24) surrounded by the jacket section (30).

9. Valve block (10) according to claim 8, characterized in that the actuator (36) has a deflectable gripper (38) which is coupled to the gripping section (32) of the closure part (24).

10. Valve block (10) according to any one of claims 5 to 9, characterized in that the jacket portion (30) of the closure part (24) has an expandable and compressible structure.

11. Valve block (10) according to one of the preceding claims, characterized in that at least in one of the valve units (12) the closure part (24) can block or open a secondary channel (18) independently of the main channel (16) and/or one or more Branches of a side channel (18) can release or block. - 16 -

12. Valve block (10) according to any one of the preceding claims, characterized in that at least some of the closure parts (24) of the valve units (12) are integrally formed with each other.

13. Valve block (10) according to claim 2 or claim 12, characterized in that at least some of the valve caps (34) of the valve units (12) are formed integrally with one another.

14. Valve block (10) according to one of the preceding claims, characterized in that connecting pieces (20) are formed in one piece with the block body (14) on the ends of the main channel (16) and the secondary channels (18) leading out of the block body (14).

15. Valve block (10) according to any one of the preceding claims, characterized in that all components of the valve block (10), with the exception of the actuators (36), are pre-sterilized and preferably pre-assembled.

16. Valve block (10) according to any one of the preceding claims, characterized in that the actuators (36) are designed so that they are controlled individually, in groups or all together.

17. Valve block (10) according to any one of the preceding claims, characterized in that the transfer of the closure part (24) from the first to the second switching position and vice versa takes place quasi-continuously.