阅读说明：本技术 生物过程流系统 (Bioprocess flow system ) 是由 K·格鲍尔 于 2019-03-21 设计创作，主要内容包括：一种用于控制被提供给生物过程流系统中的管的至少一个阀的方法,所述方法包括以下步骤：当应当允许有通过管的流时,将至少一个阀控制成第一状态,第一状态是打开状态；在过程的一些部分在系统中运行期间,将至少一个阀控制成第二状态,所述第二状态是其中提供第一关闭力的关闭状态；以及在过程的一些部分在系统中运行期间,将至少一个阀控制成第三状态,所述第三状态是其中提供第二关闭力的关闭状态,所述第二关闭力是比第一关闭力更高的力。(A method for controlling at least one valve provided to a pipe in a bioprocess flow system, the method comprising the steps of: when flow through the pipe should be allowed, controlling the at least one valve to a first state, the first state being an open state; controlling at least one valve to a second state during operation of some portion of the process in the system, the second state being a closed state in which a first closing force is provided; and during operation of some part of the process in the system, controlling the at least one valve to a third state, the third state being a closed state in which a second closing force is provided, the second closing force being a higher force than the first closing force.)

1. A method for controlling at least one valve (11; 11 '; 11' '; 11' '') provided to a pipe (3a-c) in a bioprocess stream system (1), the method comprising the steps of:

controlling (S1) the at least one valve to a first state when flow through the pipe should be allowed, the first state being an open state;

controlling (S3) the at least one valve to a second state during portions of a process operating in the system, the second state being a closed state in which a first closing force is provided; and

during operation of some portion of a process in the system, controlling (S5) the at least one valve to a third state, the third state being a closed state in which a second closing force is provided, the second closing force being a higher force than the first closing force.

2. The method according to claim 1, wherein the step of controlling the at least one valve (11; 11 '; 11 "') into the second state and the third state comprises bringing a flexible material (3; 43; 43') into sealing contact with a surface (3; 41; 41').

3. Method according to claim 1 or 2, wherein the method is a method for ensuring a reliable opening of at least one valve.

4. The method according to any one of the preceding claims, wherein the step of controlling (S3) the at least one valve (11; 11') to a second state comprises pinching the tube (3) with the first closing force, the first closing force being adapted to stop the flow in the tube at a first fluid pressure in the tube; and wherein the step of controlling (S5) the at least one valve (11; 11') into a third state comprises pinching the tube (3) with the second closing force, the second closing force being adapted to stop the flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

5. Method according to any of claims 1-3, wherein the step of controlling (S3) the at least one valve (11 "; 11") to a second state comprises moving a diaphragm (43; 43') of the valve towards a valve seat (41; 41') of the valve with the first closing force, the first closing force being adapted to stop the flow in the tube at a first fluid pressure in the tube; and wherein the step of controlling (S5) the at least one valve (11' '; 11' ' ') into a third state comprises moving a diaphragm (43; 43') of the valve towards a valve seat (41; 41') of the valve with the second closing force, the second closing force being adapted to stop the flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

6. Method according to any of the preceding claims, wherein the at least one valve (11; 11'; 11 "") is controlled into the second state when no fluid is pumped through the tube, and the valve is controlled into the third state when fluid is pumped through the tube.

7. Method according to any of the preceding claims, wherein the at least one valve (11; 11'; 11 "") is controlled into the second state or the third state in order to close the valve depending on which type of pipe is used in the system and/or depending on which application the system is used for.

8. The method according to any of the preceding claims, wherein a first closing force is provided from the at least one valve in the second state and a second closing force is provided from the at least one valve in the third state, wherein the first closing force is set to prevent fluid flow at a fluid pressure of less than 50% of the fluid pressure the second closing force is set to prevent,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 30% of the fluid pressure at which the second closing force is set to prevent,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 20% of the fluid pressure that the second closing force is set to prevent,

or wherein the first closing force is set to stop fluid flow at a fluid pressure that is less than 10% of the fluid pressure that the second closing force is set to stop.

9. Method according to any of the preceding claims, wherein in the second state a first closing force is provided from the at least one valve and in the third state a second closing force is provided from the at least one valve, wherein the second closing force is set to prevent fluid flow at a pressure of at most 20 bar or at most 10 bar or at most 5 bar.

10. Method according to any of the preceding claims, wherein the at least one valve (11; 11'; 11 "") is controlled by pneumatic air or hydraulic fluid.

11. The method of any one of the preceding claims, wherein the bioprocess stream system is a chromatography system, a filtration system, or a bioreactor system.

12. A bioprocess flow system comprising:

-at least one tube (3);

-at least one valve (11; 11'; 11 "") provided to the pipe for controlling the flow through the pipe; and

-a control system (15) configured for controlling the at least one valve (11; 11 '; 11 "') into three different states, of which a first state is an open state, wherein the tube (3) remains open so as to allow flow through the tube, and a second state and a third state are closed states preventing flow through the tube but providing different closing forces, wherein in the third state a higher closing force is provided than in the second state.

13. The bioprocess flow system of claim 12, wherein the control system (15) is configured for controlling the at least one valve (11; 11 '; 11 "") into the second and third state by bringing a flexible material (3; 43; 43') into sealing contact with a surface (3; 41; 41 ').

14. The bioprocess flow system of claim 12 or 13, wherein said at least one valve (11; 11') is a pinch valve and said control system (15) is configured for controlling said at least one pinch valve into said second state by pinching said tube (3) with a first closing force adapted to stop the flow in said tube at a first fluid pressure in said tube; and wherein the control system (15) is configured for controlling the at least one trapped tube valve into a third state by pinching the tube with a second closing force, the second closing force being adapted to stop flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

15. The bioprocess flow system of claim 12 or 13, wherein said at least one valve (11 "; 11") is a diaphragm valve and said control system (15) is configured for valving said at least one diaphragm into said second state by moving a diaphragm (43; 43') of said diaphragm valve towards a valve seat (41; 41') of said diaphragm valve with a first closing force, said first closing force being adapted to stop the flow in said tube at a first fluid pressure in said tube; and wherein the control system is configured for controlling the at least one diaphragm valve into a third state by moving a diaphragm of the diaphragm valve towards a valve seat of the diaphragm valve with a second closing force, the second closing force being adapted to stop the flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

16. The bioprocess flow system of any of claims 12-15, wherein said control system (15) is configured for controlling the state of said at least one valve (11; 11'; 11 "") into said third state with the highest closing force when said pipe should be closed so as not to allow flow through said pipe during pumping of fluid through said pipe, and for controlling the state of said at least one valve into said second state with a lower closing force when said pipe should be closed so as not to allow flow through said pipe when no fluid is pumped through said pipe.

17. The bioprocess flow system of any of claims 12-16, wherein said control system (15) is configured for controlling the state of said at least one valve (11; 11'; 11 "") into said second state or said third state, so as to close said valve depending on which type of pipe is used in said system and/or depending on which application said system is used for.

18. The bioprocess flow system of any of claims 12-17, wherein said at least one valve (11; 11'; 11 "") comprises means for controlling the state of said valve by pneumatic air or hydraulic fluid, and wherein said control system (15) is configured for controlling said pneumatic air or hydraulic fluid.

19. The bioprocess flow system of any of claims 12-18, wherein said bioprocess flow system (1) is a chromatography system, a filtration system or a bioreactor system.

20. The bioprocess flow system of any of claims 12-19, wherein a first closing force is provided from the at least one valve in the second state and a second closing force is provided from the at least one valve in the third state, wherein the first closing force is set to block fluid flow at a fluid pressure that is less than 50% of a fluid pressure that the second closing force is set to block,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 30% of the fluid pressure at which the second closing force is set to prevent,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 20% of the fluid pressure that the second closing force is set to prevent,

or wherein the first closing force is set to stop fluid flow at a fluid pressure that is less than 10% of the fluid pressure that the second closing force is set to stop.

21. The bioprocess flow system of any of claims 12-20, wherein a first closing force is provided from the at least one valve in the second state and a second closing force is provided from the at least one valve in the third state, wherein the second closing force is set to prevent fluid flow at a pressure of at most 20 bar or at most 10 bar or at most 5 bar.

22. A valve, wherein the valve (11; 11 '; 11' '; 11' '') is configured for being set into three different states, in which three different states,

the first state is an open state, wherein the tube (3) provided with the valve is kept open, so as to allow a flow through the tube;

the second state and the third state are closed states but with different closing forces, wherein the tube provided with the valve is closed against convection in both closed states but with a higher closing force in the third state than in the second state.

23. Valve according to claim 22, wherein the valve (11; 11 '; 11 "') is set in the second and third state by urging a flexible material (3; 43; 43') into sealing contact with a surface (3; 41; 41').

24. The valve according to claim 22 or 23, wherein the valve (11; 11') is a pinch valve, and,

-the second state is a closed state preventing flow through the pipe (3) provided with the valve, wherein flow is prevented by pinching the pipe with a first closing force adapted to stop flow in the pipe at a first fluid pressure in the pipe; and

the third state is a closed state preventing flow through the tube provided with the valve, wherein flow is prevented by pinching the tube with a second closing force adapted to stop flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

25. Valve according to claim 22 or 23, wherein the valve (11 "; 11" ") is a diaphragm valve (11"; 11 ""), and,

the second state is a closed state preventing flow through the tube provided with the diaphragm valve, wherein flow is prevented by moving a diaphragm (43; 43') of the diaphragm valve towards a valve seat (41; 41') of the diaphragm valve with a first closing force adapted to stop flow in the tube at a first fluid pressure in the tube; and

the third state is a closed state preventing flow through the tube provided with the diaphragm valve, wherein flow is prevented by moving a diaphragm (43; 43 ") of the diaphragm valve towards a valve seat (41; 41') of the diaphragm valve with a second closing force adapted to stop flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

26. A valve according to claim 25, wherein the diaphragm valve comprises a tube (49) for connecting the hydraulic/pneumatic chamber (47) of the diaphragm valve to a hydraulic/pneumatic control system, wherein the tube (49) comprises a sterile filter (53).

27. A valve according to any of claims 22-26, wherein the valve comprises a control system (15), the control system (15) being configured for controlling the valve to be set into the three different states.

28. A valve according to claim 26, wherein, during pumping of fluid through the pipe, the control system (15) is configured for controlling the valve (11; 11'; 11 "") into the third state with the highest closing force when the pipe (3) provided with the valve should be closed so as not to allow flow through the pipe, and for controlling the valve into the second state with a lower closing force when the pipe provided with the valve should be closed so as not to allow flow through the pipe when no fluid is pumped through the pipe.

29. A valve according to any of claims 22-28, wherein the valve comprises means for controlling the valve by pneumatic air or hydraulic fluid.

Technical Field

The present invention relates to a bioprocess flow system and to a valve and to a method for controlling at least one valve in a bioprocess flow system.

Background

In flow systems (e.g., systems for fluid transfer or fluid processing in the bioprocess industry), flexible pipes are commonly used to transport fluids in the system. The bioprocess industry includes the processing of biopharmaceuticals, vaccines, gene therapy vectors, cells, and other biological macromolecules/bioparticles, including unit operations such as cell culture, filtration, and/or chromatography. The flexible tube system, along with other plastic components such as bags and fluid handling devices, provides a cost effective solution when the flow system is deployed in a pre-sterilized state and used for single use applications where the flow system is discarded after use.

To control the fluid flow in the flexible tube, a valve is used. A common type of valve is a pinch valve, wherein a flexible tube is pinched by a valve and (correspondingly) a pinch in order to stop the flow through the tube. By opening the valve and thereby releasing the pinching and clamping forces, the tube opens reversibly and flow is allowed through the tube and its lumen. The opening of the tube is achieved by the elastic properties of the tube and the expectation that the tube assumes the original shape of the open tube and lumen of the tube. Pinch valves are very cost effective because they do not require additional valve sections outside the tube itself for fluid contact, as compared to diaphragm valves or other valve principles applied to flow systems. However, there may be problems when opening the pinch valve, especially in cases where the valve has been closed for a long time and closed with a high closing (pinching) force. This is because the opposing sides of the tube inner surface in the lumen of the tube may tend to stick together at the location of the pinch and, therefore, the tube may still close even after the valve has opened and the tube is no longer exposed to the external pinch. This may depend on the material of the tube and/or the type of fluid in contact with the inner surface of the tube prior to or during the pinching event. Obviously, the material of the inner pipe walls clamped together when pinching the pipe is similar and identical depending on the properties of the pipe. Thus, it is speculated that in some cases a certain material homogenization effect is responsible for the sticking together of the inner walls.

If the tube does not open when the valve and the actuator or grip of the valve subjecting the tube to the pinching force are open, the result will be to block flow in the pipe and interfere with or stop the fluid process taking place below. When this happens, manual squeezing and kneading of the tubes can sometimes solve the problem, but this is of course a problem, especially in automated systems.

In US9695950, a type of pinch valve is described which attempts to solve this problem. Here, the pinch valve comprises a clamping jaw which can squeeze the tube not only vertically, but also horizontally, in order to help the tube open after it has been closed.

Similar problems can occur in single-use and disposable flow systems that use plastic film plate valves rather than pinch valves. Diaphragm valves are designed as valve bodies having a rigid valve seat and a flexible diaphragm that moves onto the valve seat to stop fluid flow. The diaphragm valve may suffer from the same problem of the sealing surfaces sticking to each other, thereby preventing a smooth and controlled opening of the valve and interfering with or stopping the process. However, in contrast to pinch valves (in which the materials of the two surfaces and members that seal against each other are identical), the diaphragm and valve seat at the diaphragm valve differ in terms of the type of material or at least in terms of the material properties (e.g., elasticity).

Disclosure of Invention

It is an object of the present invention to provide an improved flow system and an improved method for controlling at least one valve in a flow system.

It is a further object of the invention to provide a streaming system and a method in a streaming system, in which the streaming in the system can be reliably controlled.

It is still a further object of the invention to provide a flow system and a method for controlling at least one valve in a flow system, whereby the risk of surfaces in the flow path at the location of the valve sticking to each other and blocking the flow even after the valve has opened is low.

This is achieved by a method, a bioprocess flow system and a valve according to the independent claims.

According to one aspect of the present invention, a method is provided for controlling at least one valve provided to a pipe in a bioprocess flow system. The method comprises the following steps:

-when flow through the pipe should be allowed, controlling the at least one valve into a first state, the first state being an open state;

-during operation of some part of the process in the system, controlling the at least one valve into a second state, the second state being a closed state in which a first closing force is provided; and

-during operation of some part of the process in the system, controlling the at least one valve into a third state, the third state being a closed state in which a second closing force is provided, the first closing force being a higher force than the first closing force.

According to another aspect of the present invention, there is provided a bioprocess flow system comprising:

-at least one tube;

-at least one valve provided to the pipe for controlling the flow through the pipe; and

-a control system configured for controlling the at least one valve into three different states, of which the first state is an open state, wherein the pipe is kept open in order to allow flow through the pipe, and the second state and the third state are closed states preventing flow through the pipe, but providing different closing forces, wherein in the third state a higher closing force is provided than in the second state.

According to another aspect of the present invention, a valve is provided. The valve is configured for being set into three different states, in which,

-the first state is an open state, wherein the pipe provided with the valve remains open, so as to allow flow through the pipe;

the second state and the third state are closed states but with different closing forces, wherein the tube provided with the valve is closed for convection in both closed states but with a higher closing force in the third state than in the second state.

Thereby, by avoiding a higher closing force than necessary, e.g. when fluid is not being pumped through a tube provided with a valve, a flow system and a method for controlling at least one valve in a flow system are provided, wherein the risk that surfaces in the flow path at the location of the valve stick to each other and thereby block flow even after the valve has been opened is low. In the case of a pinch valve, the surfaces that adhere together are the opposite inside of the flexible tube pinched by the pinch valve, and in the case of a diaphragm valve, the surfaces are the valve seat and diaphragm of the diaphragm valve. A higher closing force may be used when the system is in operation, i.e. when pumping fluid through a pipe provided with a valve, or for certain applications, and a lower closing force may be used, for example, when the system is idle, e.g. during the night. This is an easy solution to the problem of surfaces sticking together at the location of the valves, which can be achieved by using ordinary valves with minor modifications and controlling them in a new way. The fluid is suitably a liquid, such as an aqueous liquid. The fluid may in particular be an aqueous buffer or aqueous solution of biomolecules, such as proteins.

In one embodiment of the invention, the step of controlling the at least one valve into the second state and the third state comprises urging the flexible material into sealing contact with the surface.

In one embodiment of the invention, the method is a method for ensuring a reliable opening of at least one valve.

In one embodiment of the invention, the at least one valve is a pinch valve and the step of controlling the at least one valve to the second state comprises pinching the pipe with a first closing force adapted to stop flow in the pipe at a first fluid pressure in the pipe; and wherein the step of controlling the at least one valve to the third state comprises pinching the tube with a second closing force adapted to stop flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube.

In one embodiment of the invention, the at least one valve is a diaphragm valve and the step of controlling the at least one valve to the second state comprises moving the diaphragm of the valve towards the valve seat of the valve with a first closing force adapted to stop flow in the pipe at a first fluid pressure in the pipe; and wherein the step of controlling the at least one valve to the third state comprises moving the diaphragm of the valve towards the valve seat of the valve with a second closing force adapted to stop flow in the pipe at a second fluid pressure in the pipe, the second fluid pressure being higher than the first fluid pressure in the pipe.

In one embodiment of the invention, the at least one valve is controlled to the second state when fluid is not being pumped through the tube, and the valve is controlled to the third state when fluid is being pumped through the tube.

In one embodiment of the invention, the at least one valve is controlled to the second state or the third state in order to close the valve depending on which type of pipe is used in the system and/or depending on which application the system is used for.

In some embodiments of the invention, a first closing force is provided from the at least one valve in the second state and a second closing force is provided from the at least one valve in the third state, wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 50% of the fluid pressure that the second closing force is set to prevent,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 30% of the fluid pressure at which the second closing force is set to prevent,

or wherein the first closing force is set to prevent fluid flow at a fluid pressure that is less than 20% of the fluid pressure that the second closing force is set to prevent,

or wherein the first closing force is set to stop the fluid flow at a fluid pressure that is less than 10% of the fluid pressure that the second closing force is set to stop.

In some embodiments of the invention, a first closing force is provided from the at least one valve in the second state and a second closing force is provided from the at least one valve in the third state, wherein the second closing force is set to prevent the fluid flow at a pressure of at most 20 bar or at most 10 bar or at most 5 bar.

In one embodiment of the invention, the at least one valve is controlled by pneumatic air or hydraulic fluid.

In one embodiment of the invention, the bioprocess stream system is a chromatography system, a filtration system or a bioreactor system.

Further embodiments are described in the detailed description and in the dependent claims.

Drawings

FIG. 1 is a schematic diagram of a flow system according to one embodiment of the invention.

Figures 2a and 2b are schematic views of a normally closed pinch valve that may be set to three different states in accordance with one embodiment of the present invention.

Figures 3a and 3b are schematic views of a normally open pinch valve that may be set to three different states according to one embodiment of the present invention.

Figures 4a and 4b are schematic views of two diaphragm valves that can be set to three different states according to one embodiment of the present invention.

Fig. 5 is a flow diagram of a method according to an embodiment of the invention.

Detailed Description

According to the present invention, there is provided a streaming system comprising: at least one tube; and at least one valve provided to the tube for controlling flow through the tube. At least one valve is provided downstream of a flow providing device provided in the flow system or in a connected flow system. The flow providing means may for example be at least one pump or a pressure vessel. The flow system further comprises a control system configured for controlling the at least one valve into three different states. The first state of the valve is an open state in which the tube remains open to allow flow through the tube, and the second and third states of the valve are closed states that prevent flow through the tube, but provide different closing forces from the valve. A higher closing force is provided in the third state than in the second state.

The method is a method for ensuring a reliable opening of at least one valve. Further, the step of controlling the at least one valve into the second state and the third state includes urging the flexible material into sealing contact with the surface.

The valve may be a pinch valve, for example, and the control system is then configured for controlling the at least one pinch valve into the second state by pinching the tube with a first closing force adapted to stop the flow in the tube at a first fluid pressure in the tube. Furthermore, the control system is configured for controlling the at least one pinch valve into a third state by pinching the tube with a second closing force adapted to stop the flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube. Pinch valves according to two different embodiments of the present invention are described with respect to fig. 2 and 3.

In another example, the valve may be a diaphragm valve and the control system is configured for controlling the at least one diaphragm valve into the second state by moving a diaphragm of the diaphragm valve towards a valve seat of the diaphragm valve with a first closing force adapted to stop the flow in the pipe at a first fluid pressure in the pipe. Furthermore, the control system is configured for controlling the at least one diaphragm valve into the third state by moving the diaphragm of the diaphragm valve towards the valve seat of the diaphragm valve with a second closing force adapted to stop the flow in the tube at a second fluid pressure in the tube, the second fluid pressure being higher than the first fluid pressure in the tube. A diaphragm valve according to one embodiment of the present invention is described with respect to fig. 4.

The flow system according to the invention may be a system for fluid transfer or fluid treatment in the bioprocess industry. The flow system may be, for example, a bioprocess system such as, for example, a chromatography system, a filtration system, or a bioreactor system.

Fig. 1 is a schematic view of a flow system 1 according to an embodiment of the invention. The flow system 1 comprises a first pipe 3a, a second pipe 3b and a third pipe 3c for carrying a fluid in the system. The tubes 3a, 3b, 3c may be flexible tubes. The flow system according to this example comprises a first tank 5, which first tank 5 is connected by a first pipe 3a to a fluid treatment device 7. Said fluid treatment device 7 is in turn connected by a second pipe 3b to a second tank 9. The third pipe 3c is a bypass pipe for bypassing the fluid processing device 7. The fluid processing device 7 may for example be a chromatography column, a filtration device or a bioreactor. The flow system 1 further comprises a number of valves for controlling the flow through the pipes. The first pipe 3a comprises a first valve 11a and a second valve 11b and a pump 13 located intermediate said two valves 11a, 11 b. The second pipe 3b includes a third valve 11c, and the third pipe 3c includes a fourth valve 11d and a fifth valve 11 e. Furthermore, the flow system 1 comprises a control system 15, the control system 15 being configured for controlling at least one of said valves 11a, 11b, 11c, 11d, 11e into three different states depending on different situations in the flow system. The first state is an open state, wherein the pipe provided with the valve is kept open, so that flow through the pipe is allowed. The second state and the third state are closed states preventing flow through the pipe in which the valve is disposed. Different closing forces are provided from the valve for the second state and the third state, wherein in the third state a higher closing force is provided than in the second state. The valve provides a first closing force in the second state from the valve and the first closing force is adapted to stop the flow in the pipe provided with the valve at a first fluid pressure in the pipe. In a third state a second closing force is provided from the valve and adapted to stop the flow in the tube where the valve is provided at a second fluid pressure in the tube, which is higher than the first fluid pressure in the tube. As discussed above, the valve may be, for example, a pinch valve or a diaphragm valve. This will be discussed further below with respect to fig. 2-4.

By providing two different closing states of the valve (wherein different closing forces are provided), the system can be adapted to different situations, e.g. different types of pipes, different applications and different sequences or operating conditions of the process run. For example, when fluid is not being pumped through the valved tube, a second state with a lower closing force may be used, and when fluid is being pumped through the valved tube, a third state with a higher closing force may be used. In the second state, for example, when the valve should stop fluid flow under conditions of lower fluid pressure, for example, when pumping is stopped and siphoning of fluid within the flow system (due to hydrostatic pressure differences) should be prevented, a lower closing force may be used. In the second state, a lower closing force may also be used to stop the flow through the valve at a lower fluid pressure compared to the higher fluid pressure in the flow system. To stop flow under conditions of higher fluid pressure, the valve is set to a third state, in which a higher closing force is provided. The second state may be used, for example, when the system or part of the system provided with the valve is not in operation, but is filled with fluid, when waiting for other parts or operations in the system, separation process or workflow to complete, or in the event that the system pauses during the night. The third state may be used when the system or part of the system in which the valve is provided is in operation. By using the second state during times when the system is not in operation, fluid flow through the valve is still stopped and any unwanted fluid transfer (e.g. due to siphoning) is inhibited. Thus, valves provided in different parts of the system may be set to different closed states depending on whether or not those parts of the system are under high pressure (i.e., whether or not fluid is being pumped).

In one embodiment of the invention the closed state of all or at least a few valves in the flow system according to the invention is altered depending on whether the system (and e.g. the pump) is in operation or in an idle state. This embodiment of the invention allows to control and modify the supply pressure upstream of the hydraulic valve control device and to achieve a simple and cost-effective implementation of the invention, which is also applicable to conventional systems.

Thereby, the problem with surfaces sticking to each other and thus preventing opening of the valve can be alleviated, since the risk of sticking surfaces in the valve is related to the closing force and the duration of the applied closing force. In the example of a pinch valve, the inner surfaces of the tubes that are pinched toward one another when the pinch valve is closed may adhere to one another and block fluid flow even when the pinch valve is later opened. This problem with tube surfaces sticking to each other is exacerbated if higher forces are used for pinching, and if the valve is closed for a long time. The same is true for diaphragm valves in which the valve seat will adhere to the diaphragm. Higher forces and longer closing times of the valve will increase the risk of surfaces sticking to each other. Thus, by using the invention in which the closing force can be adapted to different situations, the risk of impeding the fluid flow due to surfaces sticking to each other even after the valve has been opened will be low. Especially during long closing times, when no fluid is pumped through the valved pipe, a lower closing force can be used according to the invention.

The level of the first closing force and the second closing force may be preset depending on, for example, the maximum operating fluid pressure for the flow system. The first closing force may be set to block flow at a fluid pressure that is a percentage of the maximum operating fluid pressure, or the first closing force may be set to block fluid flow at a predefined fluid pressure (e.g., a fluid pressure that is lower than the maximum operating fluid pressure, but higher than the hydrostatic pressure that would result from the fluid inlet and outlet height differences and the height difference of the connected fluid container). If the flow system and the valve are connected to a fluid source (e.g. a pressurized container or a fluid supply system) having a predefined fluid pressure or fluid pressure range during operation, which is lower than a typical operating pressure of the flow system, the first closing force may be set to prevent a fluid flow in the flow system at said pressure of the fluid source. The specific levels of the first and second closing forces may be determined by challenging the valves and piping with aqueous liquid at different pressures and determining when a leak has occurred.

In one embodiment of the invention, said first closing force is set to stop the fluid flow at a fluid pressure which is less than half the fluid pressure that the second closing force is set to stop.

In one example, the first closing force may be set to prevent fluid flow at a fluid pressure of at most 0.5 bar, and the second closing force may be set to prevent fluid flow at a fluid pressure of at most 5 bar. In another example, the second closing force may be set to prevent fluid flow at a fluid pressure of at most 10 bar.

In another embodiment of the invention, the first closing force is less than half the force of the second closing force.

By measuring the fluid pressure in the system when the system is not in operation (i.e. the pump is not pumping) and when the system is in operation, the valve can be set with the appropriate first and second closing forces.

In one embodiment of the invention, the flow system may measure the current fluid pressure at certain locations in the system and control the valve to the second closed state or the third closed state depending on these measurements. A certain time delay may be used for a change of valve state, for example to allow for a relaxation of the fluid pressure before changing the valve state for safety reasons, or to avoid frequent changes of the valve state in the middle of subsequent operations involving only a short period of idle state.

In fig. 2a and 2b, a normally closed pinch valve 11 that can be set to three different states according to one embodiment of the invention is schematically shown. In fig. 2a, a first state is shown, which is an open state. In fig. 2b, the second state or the third state is shown, both the second state and the third state being the off state. The pinch valve 11 comprises a tube pinching portion 21, the tube pinching portion 21 being arranged to be provided in connection with the tube 3 such that the tube pinching portion 21 pinches the tube 3 on the fixing portion 23. This fixed part may be part of the pinch valve 11 itself or a separate part provided in the system. The tube pinching portion 21 is connected to a piston 27 provided in a chamber 29 through a rod 25. The chamber 29 may be cylindrical. The chamber 29 is divided by the piston 27 into two parts, a first chamber part 29a and a second chamber part 29 b. A first fluid inlet 35a is provided to the first chamber portion 29a and a second fluid inlet 35b can be provided to the second chamber portion 29 b. The piston 27 is subjected to a force from a spring 31 which acts on both the piston 27 and the rear wall 33 of the second chamber portion 29 b. Thereby, the tube pinching portion 21 moves toward the tube and closes the tube to achieve the normally closed state of the valve. The resulting closing force, which will set the valve into one of its closed states (second or third state), may be selected depending on the type of spring selected and the spring force applied and in combination with the fluid pressure applied to the first and second chamber portions 29a, 29b through the first and second fluid inlet ports 35a, 35 b.

A fluid, such as a gas or a liquid, is provided in the first chamber part 29a and the pressure of the fluid inside the first chamber part 29a can be varied by introducing more fluid through the first inlet 35 a. Thereby, the piston 27 will move towards the rear wall 33 of the second chamber portion 29b and, thereby, the tube pinching portion 21 will also move away from the stationary portion 23. In fig. 2a, more fluid has been provided into the first chamber portion 29a, thereby compressing the spring 31 and moving the tube pinching portion 21 away from the fixed portion 23, i.e. opening the pinch valve, such that fluid flow is allowed through the tube 3. According to the invention, this is referred to as a first state, which is an open state.

In fig. 2b, the fluid pressure in the first chamber portion 29a is lower than in fig. 2 a. Thereby, the spring 31 is released, and the tube pinching portion 21 moves toward the fixing portion 23, and thereby, the tube 3 is pinched between the tube pinching portion 21 and the fixing portion 23. According to the invention, this is called the second state or the third state, and this is the closed state in which flow is not allowed through the tube 3. According to the invention, there are two different closing states (second state and third state), wherein different closing forces are provided by the valve. In this embodiment of the invention, these different closing forces can be achieved by controlling the fluid provided into the first chamber portion 29a at least two different levels. In another embodiment, the second inlet 35b is provided to the second chamber portion 29b, and the fluid pressure in the second chamber portion 29b can also be varied. Thereby, three different states according to the invention can be provided. A condition may suitably be provided without providing any additional fluid pressure to the chamber 29. In the embodiment shown in fig. 2a and 2b, this is the off state. Thus, the pinch valve is a normally closed pinch valve. The other closed state is provided by applying a force to the additional fluid and thereby increasing the fluid pressure in the first chamber portion 29a or the second chamber portion 29 b. In case the fluid pressure in the first chamber portion 29a is increased to provide a further closed state, which is the second state as mentioned hereinbefore, and in case the fluid pressure in the second chamber portion 29b is increased to provide a further closed state, which is the third state as mentioned hereinbefore.

In a first embodiment, a normally closed pinch valve according to fig. 2a and 2b is provided, wherein the third state and the second closing force are exerted by a spring (e.g. spring 31 in the second chamber portion 29 b). Thus, even if hydraulic fluid pressure is not applied to one or both of the first or second chamber portions 29a, 29b, the valve will stop fluid flow in the tube at a high operating pressure and in a normally closed default state. This design provides safety against possible failures or interruptions in the supply of hydraulic fluid. During operation of the valve and flow system, the valve is opened and fluid flow through the valve is achieved by applying hydraulic fluid pressure to the first chamber portion 29a so as to bring the valve into a first open state of the valve. In order to provide the second state with the first closing force of the valve and to reduce the clamping force on the pipes in the flow system, a lower hydraulic fluid pressure is applied to the first chamber portion 29a than the hydraulic fluid pressure applied to the first chamber portion 29a for the first open state. Thereby, the clamping force on the pipe is reduced compared to the third state.

In the second embodiment, the valve according to the first embodiment is controlled to its first and second states by applying different hydraulic fluid pressures to the first chamber portion 29a while the second chamber portion 29b is vented to atmosphere. The at least two hydraulic fluid pressure levels applied to the first chamber portion 29a are controlled by one pressure regulator which can be automatically controlled by the system. In another embodiment, the first chamber portion 29a is connected to two different regulators set to two different predefined hydraulic fluid pressures. When two regulators are used, one regulator is provided with a predefined hydraulic fluid pressure defining the second state, while the other regulator is provided with a predefined hydraulic fluid pressure defining the first state corresponding to an open valve. The on-off valve is used to select and determine which of two hydraulic fluid pressures is applied in order to set the valve in a first state or a second state. The on-off valve may be operated manually, however, automatic operation by the control system is preferred.

In a third embodiment, the at least two valves of the second embodiment are controlled to their first and second states by bringing them into hydraulic fluid connection with the respective regulator(s) defining the first and second states individually or simultaneously and thereby in parallel.

If the flow system is provided with different pipes, e.g. of different sizes, lumen diameters, materials, wall thicknesses, or if the flow system is provided with a mechanism to operate with different fluid pressures in the flow system, the valve according to the invention may be controlled to more than two closed states stopping the fluid flow in the flow system. Furthermore, providing different valves controlled to at least two closed states, valves may be applied which differ e.g. in terms of valve geometry and dimensions, spring load, size of the hydraulic chamber, etc., thereby limiting the dimensions.

Figures 3a and 3b are schematic views of a normally open pinch valve 11' that can be set to three different states according to one embodiment of the present invention. The only difference with the embodiment described in relation to fig. 2a and 2b is that the spring 31 is provided in the first chamber portion 29a, instead of in the second chamber portion 29b, whereby the valve is opened by the spring force when no fluid pressure is supplied to the chamber 29 b. In this embodiment, when no additional fluid pressure is provided to the chamber 29, the valve is opened and flow is allowed through the tube 3. To provide two different closed states, additional fluid is provided in two different amounts into the second chamber portion 29b through the second inlet 35b to provide two different levels of fluid pressure.

In other embodiments, the springs and spring forces shown in the above examples may be omitted, and the pinch valve operated and controlled to the three states by pneumatic fluid pressure in the two valve chambers 29a and 29 b.

In another embodiment, the valve is controlled into three states of the valve by applying different fluid pressures to only one of the chambers. For example, different fluid pressures may be applied to chamber 29b, wherein the open state of the valve is adjusted by applying a pressure below atmospheric pressure, and thereby retracting the rod 25 and grip 21, or by venting chamber 29b to atmospheric pressure such that the elasticity of the tube itself and the inherent desire of the tube to assume the original shape of the tube, open tube and lumen, urges the grip 21 and rod 25 towards chamber 29 b.

In other embodiments, the spring functionality and spring force may be imparted by other design elements and properties (such as, for example, mechanical, electrical, or magnetic properties).

Figure 4a is a schematic view of a diaphragm valve 11 "that can be set to three different states according to one embodiment of the present invention. The diaphragm valve 11 ″ is shown with connectors 45a, 45b, the connectors 45a, 45b connecting to adjacent fluid conduits, e.g., tubes that may be rigid or flexible. In another embodiment, the valve is integrated into adjacent fluid conduits upstream and downstream of the valve such that the connector and connection interface are omitted. In another embodiment, for example, the inlet and outlet of the valve may be integrally joined upstream and downstream with the fluid conduit by welding.

The diaphragm valve includes a valve seat 41 and a diaphragm 43. The process fluid is directed to pass over the valve seat 41. The diaphragm 43 may be controlled, e.g. by hydraulic or pneumatic means, to contact the valve seat 41 in order to close the valve such that fluid flow is prevented through the diaphragm valve 11 ". According to the present invention, the first state which is the open state is provided, and two closed states having different closing forces are provided. The different closing forces are provided by providing two different levels of fluid pressure against the diaphragm 43, thereby moving the diaphragm 43 at least two different levels toward the valve seat 41. A hydraulic/pneumatic chamber 47 is provided in conjunction with the diaphragm 43 for hydraulic/pneumatic control of the diaphragm 43. Remote control of the diaphragm valve 11 "may be provided by a tube 49 connected to the hydraulic/pneumatic chamber 47. A connector 51 (e.g., a sterile connector) may be connected to the other end of the tube 49 for connection to a pneumatic/hydraulic control system (15 when referring to fig. 1). In one embodiment, connector 51 may be a multi-connector that connects many pneumatic/hydraulic tubes simultaneously. In one embodiment of the diaphragm valve 11 ", a sterile filter 53 is additionally provided in the tube 49 between the hydraulic/pneumatic chamber 47 and the connector 51. The sterile filter 53 will ensure that the pneumatic/hydraulic fluid in the pneumatic/hydraulic chamber 47 is not contaminated. In one embodiment, the sterile filter is an air filter and the pneumatic/hydraulic fluid is air. Thereby, possible drawbacks due to the use of non-sterile pneumatic/hydraulic fluid from the connected pneumatic/hydraulic control system 15 can be dealt with by using the sterile filter 53.

The diaphragm valve may be provided separately or with other valves and may be provided as a pre-sterilized flow kit with the disposable flow system and sterile connectors 45a, 45b, 51. This may be provided in the bag and sterilised, for example by gamma radiation.

In one embodiment of the invention, which is suitable for both pinch valves and diaphragm valves according to the invention, air, other gases or gas mixtures are used for the control of the valves, and furthermore the control of the valves may be regulated, treated or pre-treated, such as the control of humidity, composition and aerosol content.

Air, other gases or gas mixtures may be sterilized, for example, simultaneously with sterilization of the disposable flow path. Furthermore, the air, other gases or gas mixtures provided to the system and/or to the pneumatic/hydraulic control system for controlling the valves and/or to the valves may be supplied to the system, control system or valves in a sterile filtered state.

Figure 4b shows another type of diaphragm valve 11 "' according to the present invention which can be set into three different states. In this type of diaphragm valve, the diaphragm 43 'is moved by a rod 45 onto the valve seat 41'. According to the invention, two different closing forces can be provided by the lever in order to close the valve. The position of the rod 45 and thus the diaphragm 43' may be controlled by pneumatic/hydraulic fluid. A pneumatic/hydraulic chamber 47' is provided in conjunction with the rod 45.

In one embodiment, the first (open) state of the diaphragm valves 11 ", 11" 'is controlled by applying a pressure lower than atmospheric pressure to the pneumatic/hydraulic chambers 47, 47'.

In another embodiment, the first (open) state of the diaphragm valve is facilitated by venting the pneumatic/hydraulic chamber 47, 47 'to atmospheric pressure, thus allowing the diaphragm 43, 43' to assume its natural and relaxed state in accordance with its inherent elastic properties.

In other embodiments, the first state of the valve and the corresponding force and position of the diaphragm associated with the first state are facilitated by or with other design elements and properties (such as, for example, mechanical, electrical, or magnetic properties).

According to the present invention, a control system is provided that is configured for controlling at least one valve to be set into three different states. The control system comprises means for processing and executing computer programs and means for wired or wireless communication for carrying out the control according to the invention.

The control system controls a hydraulic or pneumatic control system for controlling hydraulic/pneumatic fluid pressure that controls the state of the valve.

Further, according to the present invention, a method for controlling at least one valve provided to a pipe in a flow system is provided. A flow chart of the method is shown in fig. 5. The method steps are described in the following in order:

s1: when flow through the pipe should be allowed, the at least one valve is controlled to a first state, which is an open state.

S3: during operation of some portion of the process in the system, the at least one valve is controlled to a second state, which is a closed state in which the first closing force is provided.

S5: during operation of some part of the process in the system, the at least one valve is controlled to a third state, the third state being a closed state in which a second closing force is provided, the second closing force being a higher force than the first closing force.

The tube provided in the flow system may be a flexible tube. If a pinch valve is used, the tube needs to be flexible. The tube may be braided for high pressure applications and may be non-braided for lower pressure applications. Such flexible tubes may be made, for example, of silicone (typically platinum cured silicone or thermoplastic). These materials of common flexible pipe may tend to adhere to themselves, especially during certain conditions, and with certain fluids flowing through the pipe, and therefore, the present invention will be particularly useful for systems having these types of pipes, such as pipes made of silicone, polyolefins, and thermoplastic elastomers.

Examples of silicone tubing (preferably platinum cured silicone tubing) are Saniflex APSH (non-woven), Saniflex APST (woven). An example of a polyolefin pipe is a Tygon pipe, such as Tygon2275 IB in non-woven model. Examples of thermoplastic elastomer tubing are Advanta Flex, C-Flex 374, and SaniPure.

In the case of silicone tubing, with a solution containing sodium hydroxide (NaOH) in the pinched tube, a substance frequently used for cleaning of the flow system (at typical concentrations of 0.5-2M), a risk of sticking the tube, for example, in the pinch valve, has been observed after contact and long-term valve closure. For thermoplastic pipes, the risk of sticking the pipe in the pinch valve has been observed after contact and long-term valve closure, with water or air in the pinched pipe.

The tubes and valves of the flow system according to the invention may be provided in a closed, pre-sterilized package for installation into the system. Thus, the tube together with the valve according to the invention may possibly be pre-sterilized by gamma sterilization and be suitable for a single use.