EP2926906A1 - Valve device and fluid handling device - Google Patents

Abstract

In a valve device (30) having at least one closure means (31) and a component (33) having at least one cavity (32), wherein the closure means (31) is provided for sealing at least one opening (34) in the cavity is the valve device by centrifugal forces or equivalent forces operable. Here, the closure means (31) and the component (33) are movably mounted in response to acting centrifugal forces or equivalent forces. At least one movement-limiting means (37) is provided for the closure means (31) or the component (33) which limits the movement of the closure means or of the component when a predeterminable centrifugal force or equivalent force is exceeded.

Description

The present invention relates to a valve device having at least one closure means and a component having at least one cavity, wherein the closure means is provided for sealing at least one opening of the cavity. The valve device can be actuated by centrifugal forces or equivalent forces. Furthermore, the invention relates to the use of such a valve device and a device for handling liquids, comprising such a valve device.

State of the art

Many systems are already known for automating chemical or biochemical processes and generally for handling liquids. The German patent application DE 10 2010 003 223 A1 describes, for example, a system in which a plurality of turrets in the format of a standard centrifuge tube are arranged axially one above the other and thus can be used in a centrifuge. The turrets include channels, reaction chambers and other structures for performing fluidic unit operations. Depending on a centrifugal force, the revolvers are rotated relative to each other, with individual cavities of the various revolvers are fluidly coupled together. The liquids are thereby transported along the force vector of the centrifugal force from radially inner points to radially outer points. By changing the acceleration of the centrifuge an integrated ballpoint pen mechanism is activated, so that the revolvers arranged one above the other can be rotated against each other and individual cavities can be switched to one another. For orientation-dependent opening of cavities, for example for release single reagents, mandrels are provided at the top of a revolver, which can puncture an overlying Abdeckungsfolie at the bottom of a cavity of an overlying revolver with appropriate positioning. This system allows controlled fluid routing from pre-storage chambers via intermediary processing elements to collecting cavities for the processed liquids.

The publication of the US patent application US 2007/0134799 A1 describes a centrifugable device in which a centrifugally activatable valve is provided to control fluid flow through a reaction chamber. The valve is formed by a spring mounted on a ball, which closes an opening of a chamber from radially outside. As soon as the centrifugal force exceeds the spring force, the ball is pushed back and liquid can escape through the released opening.

Disclosure of the invention Advantages of the invention

The invention provides a multi-actuated valve device which can be actuated by centrifugal forces or equivalent forces. This valve device is particularly suitable for systems for the automated processing of liquids, for example for cartridge-based systems, which are processed in a centrifuge. The valve device according to the invention comprises at least one closure means and a component with at least one cavity. The closure means is provided for sealing at least one opening of the cavity in the component. According to the invention, the closure means and the component are movably mounted as a function of acting centrifugal forces or equivalent forces. "Equivalent forces" may be, for example, pneumatic forces caused by the application of compressed air. At least one movement limiting means (movement stop) is provided for the closure means and / or the component which controls the movement of the closure means and / or of the component when a predeterminable centrifugal force is exceeded or limited by an equivalent force. Characterized in that both the component and the closure means are mounted in principle movable, but at least one of these elements is limited in its movement, it comes at forces that trigger the movement to a different length of movement of both elements, thereby forming an opening of the previously closed cavity is reached. Preferably, the movement limiting means limits either the movement of the closure means or that of the component. In a preferred manner, the movement of the component and / or the closure means counteracts a restoring force. This can be realized for example by a spring bias of the component and / or the closure means. The restoring force is designed so that at a predefinable threshold of centrifugal force or equivalent force, the restoring force is exceeded, so that the movement of the component and the closure means is triggered and using the movement limiting means an open position of the valve device is achieved. When the centrifugal force or the equivalent force decreases, the restoring force exceeds the centrifugal force or equivalent force at a predeterminable point, so that the component and / or the closure means are moved back into the starting position, ie into the closed position.

By virtue of the multiply operable valve device according to the invention, the possibilities for the process control can be considerably expanded, for example, in a cartridge-based centrifugal system. For example, liberated fluids may be retained in a defined space for a given time before the fluids are released along the intended fluidic pathway. Several liquids can be incubated with each other. For example, it is also possible to incubate liquids with a solid phase, wherein liquids can be repeatedly passed through the valve device. These possibilities for carrying out various unit operations in biochemical processes allow the execution of complex processes in an automated manner, for example, complex binding or exchange processes or the dissolution of, for example, lyophilized substances can be carried out. The valve device according to the invention thus provides a resealable valve which offers great advantages, in particular for centrifugal systems.

In a particularly preferred embodiment of the valve device according to the invention, a further movement limiting means for the closure means and / or for the component with the at least one cavity is provided. This further movement means limits the return movement of the closure means and / or the component, which begins when falling below a predetermined centrifugal force or equivalent force and which can be supported for example by the restoring force described. By the return movement of the closure means and / or the component, the starting position or closing position of the valve device is again achieved. By the further limiting means in this case the position of the closure means and / or the component is locked in a certain position, so that the closed position is reached quickly and safely. Preferably, the further movement limiting means limits either the return movement of the closure means or that of the component.

For the realization of the valve device according to the invention, in particular two basic embodiments are advantageous. In the first basic embodiment, the movement of the closure means is limited, so that the closure means is forced by the movement limiting means in an open position. Advantageously, in this case the component is spring-biased with the at least one cavity, so that it is safely moved back to the starting position with decreasing centrifugal force or the decreasing equivalent force, resulting in a closing of the valve means. In the other basic embodiment, the movement of the component is limited so that it comes to an opening of the valve device when exceeding the predetermined centrifugal force or the same force acting. Advantageously, in this case the closure means is spring-biased, whereby it comes again to a safe closure of the valve device with decreasing centrifugal force or equivalent force.

In the former variant, the closure means is preferably designed as a spherical or conical or wedge-shaped or rod-shaped stopper. For optimal sealing of the opening of the cavity, a seal may be provided. A spherical plug is preferably located within the cavity and closes the opening from within, so to speak. A liquid present in the cavity can improve the seal by the pressure of the liquid column on the plug. Similarly, the plug may be wedge-shaped or tapered, with the tip of such a plug extending through the opening of the cavity. For a good sealing, it is advantageous if the stopper has the highest possible mass which presses into the seal. For example, for this purpose, the stopper may be made of a material having a higher density than water, for example Teflon or POM (polyoxymethylene). As the sealing material is preferably an elastic material such as rubber chosen to achieve a good press seal of the plug against the opening. An embodiment of the plug in a wedge shape, ie with an enlarged surface which is located in the interior of the cavity, is achieved in that the liquid column lying above the plug is widened so that the additional mass of the liquid column can be used for an increased contact pressure in the closed position ,

In the starting position, in which the centrifugal force or the equivalent force does not exceed a predefinable threshold value, the valve device is in the closed position. When a predefinable threshold for the acting centrifugal force or the equivalent force is exceeded, both the component with the cavity and the closure means moves in the direction of the acting force. The movement limiting means for the closure means in the first basic embodiment of the valve device according to the invention is in this case designed so that from a certain length of the movement path, the movement limiting means locks the movement of the closure means, so that only moves the component. The geometries are chosen so that in this way an opening of the valve device is achieved, wherein the closure means is pushed through the opening of the cavity through into an open position. This can be achieved, for example, by a rod-shaped movement limiting means which is smaller in diameter than the opening of the cavity and which, for example, retains the spherical plug through the opening of the cavity so that the plug no longer seals the opening. Liquids can flow around the plug through the opening and into the cavity leave. In another embodiment, in particular in the case of a conical or wedge-shaped stopper, the movement limiting means can be configured so that the tip of the stopper projecting through the opening of the cavity is retained, whereby the stopper is partially pushed out of the opening and becomes an opening and comes to a fluid flow. A spring bias of the component can be realized in this embodiment, for example, so that a spring between the component and the movement limiting means is used. If the centrifugal force or the equivalent force, which had caused an opening of the valve, falls below a predefinable threshold value, the spring force dominates, so that the component is pushed back into the starting position.

In a particularly preferred embodiment of the valve device according to the invention, the closure means is designed substantially as a rod-shaped stopper which has a liquid-permeable region in a partial length section. This longitudinal section is arranged so that this longitudinal section is in the closed position outside the cavity and outside the opening of the cavity. When the open position is reached, this section is located within the cavity opening so that fluids from the cavity can escape through this section. By acting centrifugal force or equivalent force of the plug is shifted so to speak, that the liquid can reach the continuous portion of the rod-shaped plug. The liquid-permeable region can be realized, for example, by a cross-sectionally part-circular recess in this section of the stopper. However, the partial permeability of the stopper can also be realized in other ways, for example by means of one or more bores in this section.

In particular, in the embodiment with a rod-shaped stopper with a liquid-permeable region, the already described further limiting means, which restricts the return movement of the closure means, may be advantageous. The further movement limiting means is arranged for example within the cavity and designed, for example, in the form of a movement stop. By limiting the return movement the stopper is accurately positioned in the closed position, so that the liquid-permeable area of the closure means is located outside the cavity and the sealing of the opening is assured.

In the above-mentioned second principal variant of the valve device according to the invention, the movement limiting means limits the movement of the component with the at least one cavity. Conveniently, in this embodiment, the closure means closes the cavity from the outside. When the predeterminable centrifugal force or equivalent force is exceeded, the component with the cavity is retained by the movement limiting means and the closure means moves into an open position so that liquid can leave the cavity. In a deceleration of the centrifuge or in general, when the centrifugal force or the equivalent force below a predetermined threshold, dominated by the appropriately provided restoring force acting on the closure means, so that the starting position, ie the closed position is adjusted again. With particular advantage, in this case, the already mentioned further movement limiting means for the return movement of the component is provided, so that the return movement of the component takes place only up to the correspondingly provided point. In this way, the closed position can be achieved quickly in a particularly precise manner again.

In a preferred embodiment of the valve device according to the invention, a plurality of closure means is arranged on a common carrier. For example, a plurality of closure means may be arranged on a circular support which is mounted on a common spring. By means of this closure means, several cavities of a component arranged above can be closed from below. In this case, a closure means can be provided per opening of a cavity. However, provision may also be made for a closure means to close or open a plurality of openings which are to be assigned to one or possibly more cavities.

In a particularly expedient embodiment of the valve device according to the invention, the closure means comprises a reactive surface which is to be carried out in particular for chemical or biochemical processes which are carried out with the device into which the valve device according to the invention is integrated. For example, surfaces with immobilized molecules, e.g. Antibodies, or other reactive substances may be provided, which can be used for carrying out the proposed method steps.

The closure means of the device according to the invention may be formed in one piece or two or more parts. For example, a multi-part closure means may be provided, in which one of the parts consists of a sealing material or has a sealing material. In particular, an annular element may be provided of a suitable sealing material which is combined with another component which allows complete closure of the cavity. The sealing material can form the marginal region of the respective closure means, thereby ensuring optimum sealing of the opening of the cavity.

The valve device according to the invention is suitable in a particularly advantageous manner as part of a centrifugal system, with the valve device according to the invention a repeated actuation of the valve is possible. The valve device thus considerably expands the possibilities, in particular of a cartridge-based centrifugal system, for the automated performance of, for example, biochemical or chemical processes. Such a centrifugal system is based in particular on two or more axially superimposed bodies (revolvers), which are rotatable relative to one another in dependence on a centrifugal force or an equivalent force. Herein, by "equivalent force" is meant that the force, when applied to the system, causes the bodies to rotate in relation to one another as provided by a corresponding mechanism. This can be achieved for example by applying a pressure (compressed air). For the twisting mechanism of such a device, for example, a so-called ballpoint pen mechanism may be provided, wherein an engagement of Guide springs of a body in a row of teeth of the other body and a counter to the centrifugal force or against the equivalent force acting restoring force of the body is provided.

The invention further comprises the use of the described valve device for a system for handling liquids, which system comprises a plurality of bodies arranged axially one above the other and which are rotatable relative to one another in dependence on a centrifugal force or an equivalent force. Finally, the invention comprises a device for handling liquids with a plurality of axially superposed bodies (revolvers), which are rotated in response to a centrifugal force or equivalent force against each other. According to the invention, this device comprises at least one valve device, as described herein. The individual bodies or revolvers of the device each have at least one cavity. As a result of the rotation of the revolvers with respect to one another, the individual cavities can be fluidly coupled to one another. According to the invention, at least one of these fluidic couplings is realized by means of the valve device according to the invention. This valve device is to be operated via the adjustable acceleration changes of the centrifuge or an equivalent force. The great advantage of this is that this operation, so the opening and closing of the valve, several times and in principle unlimited times can be performed, whereby the possibilities of such a device are considerably expanded.

Further features and advantages of the invention will become apparent from the following description of exemplary embodiments in conjunction with the drawings. In this case, the individual features can be implemented individually or in combination with each other.

Fig. 1A/B

schematische Darstellungen einer beispielhaften Ausgestaltung einer erfindungsgemäßen Ventileinrichtung mit kugelförmigem Verschlussmittel;

Fig. 2A/B

schematische Darstellungen einer erfindungsgemäßen Ventileinrichtung mit keilförmigem Verschlussmittel;

Fig. 3A-C

schematische Darstellungen einer erfindungsgemäßen Ventileinrichtung mit stabförmigem Verschlussmittel;

Fig. 4

Schnittdarstellung einer beispielhaften Ausgestaltung eines flüssigkeitsdurchlässigen Bereiches eines Verschlussmittels für eine erfindungsgemäße Ventileinrichtung;

Fig. 5A-C

schematische Darstellungen der Integration einer erfindungsgemäßen Ventileinrichtung in den Revolver eines Zentrifugalsystems für ein Bead-basiertes Prozessierungsprotokoll;

Fig. 6

zeitlicher Verlauf der Zentrifugationsschritte für ein Bead-basiertes Prozessierungsprotokoll;

Fig. 7A-C

schematische Darstellungen einer beispielhaften Ausgestaltung einer erfindungsgemäßen Ventileinrichtung mit federkraftunterstütztem Verschlussmittel;

Fig. 8A/B

isometrische Außenansicht (A) und Schnittansicht (B) einer beispielhaften Ausgestaltung der Körper eines Zentrifugalsystem mit erfindungsgemäßer Ventileinrichtung;

Fig. 9A/B

isometrische Darstellungen einer erfindungsgemäßen Ventileinrichtung mit einer Mehrzahl von Verschlussmitteln und

Fig. 10A/B

isometrische Darstellungen einer erfindungsgemäßen Ventileinrichtung mit einer Mehrzahl von mehrteilig zusammengesetzten Verschlussmitteln.

In the figures show:

Fig. 1A / B

schematic representations of an exemplary embodiment of a valve device according to the invention with spherical closure means;

Fig. 2A / B

schematic representations of a valve device according to the invention with wedge-shaped closure means;

Fig. 3A-C

schematic representations of a valve device according to the invention with rod-shaped closure means;

Fig. 4

Sectional view of an exemplary embodiment of a liquid-permeable region of a closure means for a valve device according to the invention;

Fig. 5A-C

schematic representations of the integration of a valve device according to the invention in the turret of a bead- based processing protocol centrifugal system;

Fig. 6

time course of the centrifugation steps for a bead- based processing protocol;

Fig. 7A-C

schematic representations of an exemplary embodiment of a valve device according to the invention with spring-assisted closure means;

Fig. 8A / B

Isometric view (A) and sectional view (B) of an exemplary embodiment of the body of a centrifugal system with valve device according to the invention;

Fig. 9A / B

Isometric views of a valve device according to the invention with a plurality of closure means and

Fig. 10A / B

Isometric representations of a valve device according to the invention with a plurality of multi-part composite closure means.

Description of exemplary embodiments

Fig. 1 schematically shows the principle of operation of an example of a valve device 10 according to the invention with a spherical plug 11 as a closure means. The plug 11 is located within the cavity 12 of a component 13 Fig. 1A illustrated starting position of the plug 11 seals an opening 14 of the cavity from (closed position). The seal is supported by a sealing ring 15 in particular of a flexible material. The contact pressure of the stopper 11 supporting liquid column 16 within the cavity 12 is shown hatched. In Fig. 1B is the open position shown in which an acting centrifugal force or equivalent force exceeds a predetermined threshold. In this case, the component 13 as well as the closure means 11 contained therein moves along the force vector in the example of an acting centrifugal force from a radially inner point within a centrifuge rotor to a further outward point. The movement limiting means 17, which is arranged below the closure means 11, limits the movement of the closure means 11. In this embodiment, the movement limiting means 17 is configured inverted T-shaped, wherein the movement limiting means 17 engages the opening 14 of the component 13 and thereby the movement of the closure means 11 limited. This part of the movement limiting means 17 is smaller in cross section than the opening width of the opening 14, so that liquid can escape through the opening 14. The valve is thus in an open position. The fluid flow is indicated by two arrows. Between the component 13 and the movement limiting means 17, a spring 18 is arranged, which presses the component 13 back to the starting position with decreasing centrifugal force or equivalent force, so that the in Fig. 1A shown closed position is reached again.

Fig. 2 illustrates another example of a valve device 20 according to the invention. In this embodiment, the closure means 21 is wedge-shaped. The tip of the wedge-shaped designed closure means 21 protrudes through the opening 24 of the cavity 22 of the component 23 therethrough. The seal is supported by a sealing ring 25. In Fig. 2A the closed position is shown, in which the fluid column 26 resting on the wedge-shaped closure means 21 contributes to the contact pressure. When the acting centrifugal force or a equivalent force exceeds a certain threshold, move the member 23 and the closure means 21 against the spring force 28 down. The resulting open position is in Fig. 2B shown, wherein the movement of the closure means 21 is limited by the movement limiting means 27, so that the closure means 21 is pushed out of the sealing position and liquid, indicated here by two arrows, can escape.

Fig. 3 illustrates another example of a valve device 30 according to the invention. Here, the closure means 31 is designed rod-shaped. The rod-shaped cross section of the closure means 31 closes the opening 34 of the cavity 32 of the component 33 (FIG. Fig. 3A ). The seal is optimized by a sealing ring 35. In the lower region of the rod-shaped closure means 31 there is a liquid-permeable region 39. With sufficient centrifugal force or equivalent force, the rod-shaped stopper 31 and the component 33 are moved downwards, the movement of the closure means 31 being limited by the movement limiting means 37 ( Fig. 3B ). As a result, the closure means 31 and the component 33 are displaced relative to one another such that the liquid in the cavity 32 can reach the continuous region 39 of the closure means 31 (open position). When decelerating the rod-shaped plug 31 and the component 33 are pressed by the acting spring force 38 back in the opposite direction ( Fig. 3C ). In this case, the movement of the closure means 31 is limited by the further movement limiting means 41 arranged above, so that the permeable region 39 of the stopper 31 lies below the opening of the cavity or below the seal 35. In this position, the valve is closed again.

In the return movement of the component, it can generally be provided that the spring 38 acts directly only on the component 33. However, it is expedient that the plug 31, for example, by a press fit, which causes a seal, is relatively firmly connected to the component 33, so that the plug is also moved during the return movement of the component. In other embodiments, it is also possible that the spring force acts directly on the component and the closure means.

Fig. 4 illustrates a possibility for the design of the liquid-permeable region 39 of FIG Fig. 3 shown bar-shaped closure means 31. In Fig. 4 is a section through the liquid-permeable longitudinal portion 39 of the closure means 31 is shown, wherein a recess 42 is provided in the edge region, through which in the open position of the valve means, the liquid can flow. The liquid-permeable longitudinal section, which is preferably arranged terminally, can occupy, for example, about one third or about half the length of the closure device.

A valve device according to the invention can be used, for example, in a centrifugal system for the automated processing of bead- based assays. For a maximum interaction of the beads with the reagents, for example for adsorption or for a reaction of interaction partners, a certain exchange time is often necessary (incubation time). The requirements for optimal process control can be realized in a particularly advantageous manner by means of a valve device according to the invention. In particular, this can ensure that the beads are repeatedly brought into contact and mixed with the liquid surrounding them. Fig. 5 illustrates the integration of a valve device according to the invention into a system for a bead- based application. Here, a valve device with a rod-shaped plug 51, with the in Fig. 3 illustrated embodiment of the valve device is integrated into a revolver 500 for a centrifugal system. With this system, optimum mixing of the beads 501, which are mounted in a cavity 502 of a component 503 within the revolver 500, can be achieved. The beads 501 are, in particular, magnetic beads. Without acting centrifugal force or at low centrifugal force (ω <ω ₂ ), the beads are attracted by a magnet 510 and are located close to the magnet ( Fig. 5A ). With medium centrifugal force (ω> ω ₃ ), the beads are again centrifuged into the liquid phase ( Fig. 5B ). During spin-off, beads 501 traverse the liquid phase, allowing for exchange. Without or with low centrifugation, the beads 501 collect again on the magnet 510. The cavity 502 with the beads 501 has an opening with a sealing ring 55. In the starting position ( Fig. 5A ) is the opening through the Plugs 51 according to the invention closed. The valve plug 51 is pushed up together with the component 503 by the spring tension 508, the valve being closed. The liquid-permeable region 59 of the plug 51 is located below the seal 55. In a medium-strength centrifugation ( Fig. 5B ), the beads 501 can no longer be held by the magnet 510 and fall back into the well (cavity) 502 and mix with the liquid. The centrifugal force has not yet reached the threshold required for activation of the valve device, so that the rod-shaped stopper 51 holds the sealing position. The valve thus remains closed. In developments, it can be provided that the closure means 51 in the upper region, which is in the closed position above the opening or the seal, has a widening in order to secure the sealing position. Between the positions in FIGS. 5A and B can be changed periodically to achieve a good mixing of the beads with the surrounding liquid. Fig. 5C shows the situation with a strong centrifugation (ω> ω ₄ ), ie with a centrifugal force above a certain threshold value. In this case, the component 503 and the plug 51 move so far down that the plug 51 comes into contact with a movement limiting means 57 and is retained in its further movement, whereby the component 503 and the plug 51 are shifted relative to each other liquid-permeable region 59 of the plug 51 in the region of the opening or the sealing ring 55 is located. The plug 51 is raised relative to the bottom of the component 503. In this situation, the valve is open and liquid can escape from the cavity of the component 503. Subsequently, the valve can be closed again by deceleration below ω <ω ₂ and the beads can be incubated with further liquids. When decelerating ( Fig. 5A ), the plug 51 is pressed against an upper movement stop 61 (movement limiting means). This results in that the permeable portion 59 of the plug 51 is again below the seal 55 (closed position).

Fig. 6 shows an exemplary centrifugation protocol for performing a bead-based incubation. Here, a first centrifugation ω> ω ₂ triggers a first rotation of the already mentioned ballpoint pen mechanism of FIG Centrifugal system, which is completed by decelerating with ω <ω ₁ (1 → 1 '). In this switching process, liquid can be transferred from a revolver arranged above into a cavity of a further revolver located radially further inside. In terms of in Fig. 5 illustrated embodiment of a revolver of such a centrifugal system here stings a mandrel 511 on top of the revolver 500 a sealing film on the underside of a cavity of an overlying revolver, so that liquid can flow into the cavity 502 of the revolver 500. By further accelerating to ω> ω ₂ , a further liquid is transferred into the cavity 502 of the revolver 500 (2). Increasing the centrifugal acceleration to ω> ω _{2 also} causes the component 503 (mixing trough) to move downwardly, as shown in FIG Fig. 5B is shown. In this case, the beads 501 are released from the magnet 510 and moved through the liquid by the medium-strength centrifugal forces. A subsequent deceleration to ω ₂ >ω> ω ₁ causes the trough 503 is moved by the spring force 508 up to the stop again. The beads 501 collect again at the magnet 510. However, since centrifugal acceleration of ω> ω _{1 is still} maintained, the switching process of the ballpoint pen mechanism, that is, the twisting mechanism, unlike the first centrifugation pulse (1 → 1 '), does not yet completed. The acceleration change between ω ₂ >ω> ω ₁ and ω ₄ >ω> ω ₃ is repeated several times in the sequence in order to increase the mixing effect. After mixing, the valve device is opened by centrifugation on ω> ω ₄ ( Fig. 5C ), wherein the plug 51 is moved upwards in relation to the seal 55. The valve opens and the liquid from the cavity 502 is passed through the opened valve during centrifugation. Subsequently, the centrifugation acceleration is reduced to ω <ω ₂ . By the action of the spring 508, the component 503 and the plug 51 are moved back and the plug 51 abuts the upper movement stop 61 and is thus pressed into the seal 55. Subsequently, it is decelerated to ω <ω ₁ to complete the second switching process of the twisting mechanism (2 → 2 ').

$$\mathrm{200}\mathrm{g}<{\mathrm{\omega }}_2<\mathrm{600}\mathrm{g}$$

$$\mathrm{50}\mathrm{g}<{\mathrm{\omega }}_{\mathrm{3}}<\mathrm{3000}\mathrm{g}$$

$$\mathrm{3000}\mathrm{g}<{\mathrm{\omega }}_{\mathrm{4}}<\mathrm{6000}\mathrm{g}$$

A determination of the critical acceleration ω ₁ , ω ₂ , ω ₃ and ω ₄ depends in particular on the springs used and the properties of the respective cartridge mechanism and overall of the spring system. For example, the critical accelerations can be selected from the following ranges, wherein it should be noted that ω ₁ <ω ₂ <ω ₃ <ω ₄ should apply: $$\mathrm{20}\mathrm{G}<{\mathrm{\omega }}_{\mathrm{1}}<\mathrm{150}\mathrm{G}$$

$$\mathrm{200}\mathrm{G}<{\mathrm{<figure-callout\; id="2"\; label="\omega "\; filenames="imgf0006.png"\; state="\{\{state\}\}">\omega </figure-callout>}}_2<\mathrm{600}\mathrm{G}$$

$$\mathrm{50}\mathrm{G}<{\mathrm{\omega }}_{\mathrm{3}}<\mathrm{3000}\mathrm{G}$$

$$\mathrm{3000}\mathrm{G}<{\mathrm{<figure-callout\; id="4"\; label="\omega "\; filenames="imgf0006.png"\; state="\{\{state\}\}">\omega </figure-callout>}}_{\mathrm{4}}<\mathrm{6000}\mathrm{G}$$

Fig. 7 11 schematically illustrates another example of a valve device 70 according to the invention. The valve device 70 is essentially formed by a component 73 which contains two cavities and two closure means 71 which close openings of the cavities 72. The closure means 71 are mounted on a common spring 78. The downward movement of the component 73 is limited by a first movement limiting means 77. The movement of the component 73 upwards is limited by a further movement limiting means 81. In the in Fig. 7A the situation shown acts both a centrifugal force F _z and the spring force F _F. However, the centrifugal force does not exceed the spring force. The valve is closed. During a stronger acceleration ( Fig. 7B ), the component 73 and the closure means 71 move radially outwards (in this illustration downward), wherein the centrifugal force dominates and the spring 78 is compressed. If a critical acceleration is exceeded, the component 73 reaches the movement limiting means 77 and is retained, so that only the closure means 71 move further radially outward. In this case, the cavities 72 of the component 73 open and liquid can escape. During the deceleration of the centrifuge, the clamping force of the spring 78 presses the closure means 71 and also the component 73 radially inwards (in this illustration upward) until the cavities 72 of the component 73 are closed again ( Fig. 7C ). The upper movement limiting means 81 causes the system to quickly reach this starting position again and the closing position is locked.

An integration of this principle of a valve device according to the invention in a centrifugally controlled cartridge mechanism is in Fig. 8 illustrated. Shown is an upper turret 810, a middle turret 820, and a portion of a lower third turret 830, which are components of a cartridge-based centrifugal system. In this case, fluid passages of the central revolver 820 are closed or opened by valve devices according to the invention. Thus, in a centrifugally controlled manner, liquids can be brought into contact with each other or liquids with a reactive surface for a defined time. Fig. 8A shows the relative position of the individual revolvers 810, 820, 830 to each other, wherein cavities on the underside of the central turret 820 can be closed and opened by closure means 801 according to the invention. The closure means 801 are arranged on a common carrier 850. The carrier 850 is mounted on a spring 808. Fig. 8B shows a cross section through the central turret 820 and the carrier 850 with the closure means 801. The carrier 850 with the closure means 801 forms part of the lower turret 830. The closure means 801 close from below several channels 802 of the central turret 820. The closure means 801 advantageously consist partially or completely of a soft and flexible material, which, in addition to its function as a seal at the same time withstand the pressure of the liquids and the centrifugal force. Suitable examples are silicone or other polymers.

Fig. 9 shows the carrier 850 with a total of eight closure means 801 in an isolated representation. The carrier 850 is composed essentially of two elements. A first element 851 carries the actual closure means 801. A second element 852 serves to insert the element 851 with the closure means 801 (FIG. Fig. 9A ). Overall, this forms a structure which is suitable for receiving the liquids released by the valve devices according to the invention and for passing these liquids into subsequent processing stages ( Fig. 9B ). Each closure means 801 functions as part of a separate valve. Overall, in a sense, eight valves are arranged in a circle.

In preferred embodiments, the closure means 801 may be provided with reactive surfaces. It can be provided, for example, that the closure means 801 is at least partially formed from a polymer, which at the same time represents the reactive surface. On the other hand, various coatings or the like of the closure means 801 are possible. Reactive surfaces can be used, for example, for carrying out immunoassays. For example, immobilized antibodies used for the detection of certain antigens in the context of immunoassays can be used as reactive surfaces. Such immunoassays require repeated incubations of various substances with one another and optionally with a reactive surface. With the valve devices according to the invention, such repeated incubations of liquids with a reactive surface can be carried out in a particularly advantageous manner. Here, in centrifugally controlled manner, different liquids can be brought into contact with each other or liquids with the reactive surface for a defined time.

Fig. 10 shows an example in which the closure means 901 itself are formed of two components 910, 920, which are arranged on a common carrier 950. Here, a first component 910 comprises an inert sealing material. This component takes over the actual sealing function. Another component 920 completes the closure means 901 (FIG. Fig. 10A ). Fig. 10B shows the assembled shape of the closure means 901, in which the sealing material of the component 910, the closure means 901 enclosing a ring. The component 920 is made of a polymer material, for example. Preferably, the polymeric material provides a reactive surface or the component 920 acts as a reactive surface support.

Claims (15)

Valve device (10; 20; 30; 70) having at least one closure means (11; 21; 31; 51; 71; 801; 901) and a component (13; 23; 33; 503; 73) having at least one cavity (12; 22, 32, 502, 72, 802), the closure means being provided for sealing at least one opening (14, 24) of at least one cavity in the component and wherein the valve means is actuable by centrifugal forces or equivalent forces, characterized in that Locking means (11; 21; 31; 51; 71; 801; 901) and the component (13; 23; 33; 503; 73) are movably mounted in response to acting centrifugal forces or equivalent forces, at least one movement limiting means (17; 37; 57; 77) for the closure means (11; 21; 31; 51; 71; 801; 901) and / or the component (13; 23; 33; 503; 73) which controls the movement of the closure means and / or the component when exceeding a predetermined centrifugal force or equivalent force limited , Valve device according to claim 1, characterized in that the movement of the component (13; 23; 33; 503; 73) and / or the closure means (11; 21; 31; 51; 71; 801; 901) counter to a restoring force (18; 28, 38, 508, 78, 808). Valve device according to claim 1 or claim 2, characterized in that a further movement limiting means (41; 61; 81) is provided for the closure means (31; 51) and / or the component (73) which permits a return movement of the closure means and / or the Limited component below a predetermined centrifugal force or equivalent force. Valve device according to one of the preceding claims, characterized in that the closure means is a spherical (11) or cone-shaped or wedge-shaped (21) or rod-shaped (31; 51) stopper and in that the movement limiting means (17; 27; 37; 57) controls the movement of the stopper Limited closing means. Valve device according to claim 4, characterized in that the movement limiting means (17; 27; 37; 57) presses the closure means through the opening of the cavity in an open position when the predetermined centrifugal force or equivalent force is exceeded. Valve device according to claim 5, characterized in that the closure means is a rod-shaped stopper (31; 51) which in a longitudinal section has a liquid-permeable region (39; 59) which permits a passage of liquids only in the open position. Valve device according to Claim 6 in conjunction with Claim 3, characterized in that the return motion of the closure means (31; 51) is limited by the further movement limiting means (41; 61) such that the liquid-permeable region (39; Cavity (32; 502) is located. Valve device according to one of claims 1 to 3, characterized in that the closing means (71; 801; 901) closes the cavity (72; 802) from the outside and that the movement limiting means (77) limits the movement of the component (73) Exceeding the predetermined centrifugal force or equivalent force the closure means moves due to the limitation of movement of the component in an open position. Valve device according to claim 8 in conjunction with claim 3, characterized in that by the further movement limiting means (81) the return movement of the component is limited in such a way (73) that a closing position is achieved by the return movement of the closure means (71). Valve device according to claim 8 or claim 9, characterized in that a plurality of closure means (801; 901) is arranged on a common carrier (850; 950). Valve device according to one of the preceding claims, characterized in that the closure means (801; 901) comprises a reactive surface, wherein preferably the reactive surface is provided for chemical or biochemical processes to be carried out. Valve device according to one of the preceding claims, characterized in that the closure means (901) is formed in two or more parts, wherein preferably a part of the closure means comprises a sealing material (910) which is arranged in particular in a peripheral region of the closure means. Valve device according to one of the preceding claims, characterized in that the valve device is part of a centrifugal system on the basis of axially superimposed bodies (810; 820; 830), wherein the bodies are rotated against each other in dependence on a centrifugal force or equivalent force. Use of a valve device according to any one of the preceding claims for a system for handling liquids having a plurality of axially superposed bodies (810; 820; 830) which are rotatable relative to one another in response to a centrifugal force or equivalent force. Device for handling liquids with a plurality of axially superimposed bodies (810; 820; 830), depending on of a centrifugal force or an equivalent force against each other, characterized in that the device comprises at least one valve device (10; 20; 30; 70) according to one of claims 1 to 13.

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