Microfluidic membrane valve, in particular for a microfluidic cartridge for the detection of pathogens

Abstract

The invention relates to a microfluidic membrane valve (100), in particular for a microfluidic cartridge (200) for detecting pathogens. The membrane valve (100) is closed by a membrane (130) resting at least partially on a valve seat (115), the membrane (130) being stretched and preferably prestressed by the valve seat (115) in the resting state. Furthermore, the invention relates to a microfluidic cartridge (200) comprising such a membrane valve (100) and to a method (500) for producing such a membrane valve (100).

Description

State of the art

[0001] Microfluidic (PCR) systems, such as the Vivalytic® platform from Robert Bosch GmbH, can be used to detect pathogens such as influenza or coronaviruses. Such systems often comprise microfluidic cartridges for collecting and processing a biological sample and an analysis device into which the cartridges are placed for processing. The cartridges contain typical elements for microfluidic unit operations, such as channels, chambers, and valves, which are operated via mechanical or pneumatic actuators of the analysis device.

[0002] The valves are often designed as membrane valves (referred to in English as membrane valves or diaphragm valves), in which the valve can be opened or closed by moving or stretching the membrane, as shown, for example, in the patent specification US 7 607 641 B1 and the patent application US 2023 / 0226547 A1. Disclosure of the inventionAdvantages of the invention

[0003] Against this background, the invention relates to a microfluidic diaphragm valve, wherein the diaphragm valve is closed by a diaphragm resting at least partially on a valve seat, wherein the diaphragm is stretched and preferably prestressed by the valve seat in the resting state. The invention also relates to a microfluidic device, in particular a microfluidic cartridge, with one or more diaphragm valves according to the invention.

[0004] The diaphragm valve can in particular be a normally closed valve, i.e. a diaphragm valve which is closed in the resting state.

[0005] The diaphragm valve preferably comprises a valve body, which has the valve seat and, at least in part, the fluid channels separated from one another by the valve seat. The valve body can preferably be made of a rigid or hard material, for example, polycarbonate, with the valve seat and / or the fluid channels separated from one another by the valve seat being formed by recesses, in particular by milling or drilling, in the material.

[0006] The valve seat can, in particular, be an elevation or a projection, wherein a part of a surface of the valve seat contacts the diaphragm in the resting state. In other words, the diaphragm rests on the valve seat, in particular on the part of the surface of the valve seat, in the resting state. The valve seat preferably separates a first fluidic region, in particular a first fluid channel, from a second fluidic region, in particular a second fluid channel, such that when the diaphragm rests on the valve seat or on the part of the surface, there is no fluidic connection between the first fluidic region and the second fluidic region, i.e. the valve is closed.

[0007] The preload according to the invention advantageously enhances the normally closed function of the valve. This has the advantage that the valve is less likely to open unintentionally, for example, due to the valve being filled with fluid or due to a particularly sudden movement of the entire valve due to external forces. Preload in the resting state specifically means that the diaphragm is mounted in the valve in such a way that it is stretched in the area of ​​the valve seat compared to the relaxed state. A relaxed state specifically refers to the state without any force acting on the diaphragm.

[0008] Preferably, the height of the valve seat is selected such that the diaphragm, which is fixed in certain places in the diaphragm valve, is stretched by the valve seat at the location of the valve seat and thus prestressed. In particular, the diaphragm is arranged relative to the valve seat such that an upper side of the valve seat bulges the diaphragm in certain areas and thus prestresses it. For this purpose, the diaphragm can be fixed at at least two locations in the diaphragm valve spaced from the valve seat, in particular at two locations in the diaphragm valve opposite the valve seat.

[0009] The diaphragm valve is preferably formed by at least three parts, in particular by the above-described valve body, which has the valve seat, as the first part and a second part, wherein the diaphragm is arranged and in particular clamped between the valve body and the second part as the third part. For actuation of the diaphragm valve, the second part preferably has a channel for applying negative or positive pressure to the diaphragm in a region of the valve seat. The first part and the second part can be formed from two layers, in particular arranged in parallel. The diaphragm valve can be part of a microfluidic device, in particular a microfluidic cartridge.If the cartridge has a layered structure with two layers, for example made of plastic such as polycarbonate, and a membrane in between, for example made of plastic such as thermoplastic polyurethane (also referred to as a cartridge membrane), the membrane valve can be formed directly in these layers, wherein the first part of the valve is formed in the first layer and the second part in the second layer and the cartridge membrane is used in the region of the valve as the membrane of the valve.

[0010] In an advantageous embodiment, an area of ​​the valve seat that contacts the diaphragm in the closed state has a coating for adhering the diaphragm. This advantageously enhances the seal in the closed state, for example, by reducing the topography or roughness on the valve seat, i.e., in particular, by smoothing the area that contacts the diaphragm, or by providing fluid-repellent, particularly hydrophobic, properties. A fluorinated polymer, for example, can be used as the coating.

[0011] According to a particular development, a part of the valve seat facing the membrane has a different material composition than the rest of the valve seat, which in particular comprises a base of the valve seat. Alternatively, this part is designed as a separate component. This has the advantage that desired properties of this part, such as a particular smoothness of a surface of the part, can be optimized independently of the rest of the valve and in particular independently of the valve seat by appropriately selecting the materials for the attachment and / or a separate manufacturing process. For example, a flexible material such as an elastomer or a thermoplastic elastomer can be used. This has the advantage that the sealing effect in the closed state is further increased. In a further example, a hydrophobic polymer can be used.This has the advantage that the sealing effect in the closed state is improved by the water-repellent properties of the valve seat. The separate component can be inserted or fitted. The separate component can also be manufactured in a single production step with the remaining valve seat, valve body, and / or other parts of the diaphragm valve, for example, by two-component injection molding.

[0012] According to a special embodiment, the diaphragm is detachably connected to the valve seat at least in places. This means that during initial use, a minimum force dependent on the strength of the connection must be exerted on the diaphragm in order to release the connection. This advantageously significantly reduces the risk of unintentional opening and thus unintentional fluid transport before intended use, for example due to vibration during production or transport. The connection can be realized in particular via a material-to-material connection such as gluing or welding. In particular, if the valve seat is at least partially transparent, the connection can be realized by welding using a laser transmission welding process.The weld is dimensioned so that detachment can be achieved, preferably without damage or fracture edges to the valve seat or diaphragm. This can be achieved, for example, by selecting a low energy input, such as laser energy, or by welding only over a small portion of the valve seat surface. For example, the welding is only spot-welded with a diameter between 50 µm and 500 µm. In another example, the welding is linear across the width of the valve seat, with the weld width then being, for example, between 50 and 500 µm.

[0013] According to a further embodiment, the detachable connection between the membrane and the valve seat is achieved by the membrane and the valve seat being connected to each other by lamination over the entire or only part of the surface of the valve seat.

[0014] The invention thus also relates to a method for producing a microfluidic diaphragm valve. For this purpose, a valve body with a valve seat and an at least partially expandable diaphragm are provided, wherein the valve seat can be formed by a recess in the valve body. The valve body and valve seat can be manufactured by an injection molding process, in particular as a one-piece component. The diaphragm is then arranged relative to the valve body in such a way that an expandable region of the diaphragm is stretched and thus prestressed by the valve seat. Short description of the drawings

[0015] Embodiments of the invention are schematically illustrated in the drawings and explained in more detail in the following description. The same reference numerals are used for the elements shown in the various figures and have a similar effect, and a repeated description of the elements is omitted.

[0016] It shows Fig. 1, Fig. 2 embodiments of the microfluidic membrane valve according to the invention, in particular as part of a microfluidic cartridge according to the invention, and Fig. 3 a flowchart of an embodiment of the method according to the invention. Embodiments of the invention

[0017] Fig. 1a and Fig. 1b shows an embodiment of a diaphragm valve on which the invention is based. The diaphragm valve can comprise a valve body made of a rigid material with at least two fluidic channels and a flexible diaphragm, the actuation of which provides fluidic connection or separation between the two channels. The diaphragm can be actuated pneumatically via a third channel in the valve body. Fig. Figure 1a shows an example of such a diaphragm valve 10 with a valve body 19, for example made of polycarbonate (PC), and a diaphragm 18, for example made of thermoplastic polyurethane (TPU). The valve body 19 has an inlet fluid channel 11 and an outlet fluid channel 12, which are separated from one another by a valve seat 15 and a first diaphragm side 16 of the diaphragm 18, which lies against the valve seat 15 and thereby closes the two channels 11, 12. A third fluid channel 13 opens at the second diaphragm side 17 facing away from the valve seat 15. By applying a negative pressure via the third fluid channel 13, the diaphragm 18 can be partially sucked into the third channel 13 and thus, as in Fig. 1b, can be moved away from the top side 14 of the valve seat 15, so that fluid can be conveyed between the valve seat 15 and the diaphragm 18 from the first fluid channel 11 into the second fluid channel 12 and vice versa. Since this diaphragm valve 10 is closed in the rest state, which is characterized by the absence of externally applied forces, it is also referred to as a normally closed valve. In the alternative case of the normally open valve, the diaphragm 18 could, for example, be arranged at a distance from the valve seat 15 and pressed against the valve seat 15 by applying excess pressure in the third fluid channel 13 to close the valve 10.

[0018] Based on this diaphragm valve 10 shows Fig. 2 shows an embodiment of the diaphragm valve 100 according to the invention, which is arranged in an embodiment of a cartridge 200 according to the invention. Fig. 3 shows a flowchart of an embodiment of the method 500 according to the invention, for example, to Fig. 2 to produce the diaphragm valve 100 shown.

[0019] The diaphragm valve 100 comprises, for example, three parts, namely a first substrate part 110 with the valve seat 115, a second substrate part 120 and a diaphragm 130 arranged between the two substrate parts 110, 120.

[0020] The two substrate parts can each be part of a layer, ply, or carrier plate of the cartridge 200 according to the invention, which is realized in a layered structure. The two substrate parts 110, 120 can be made of an amorphous plastic, such as polycarbonate in particular. The membrane 130 of the diaphragm valve 100 can also be part or a region of a membrane of the cartridge 200 and can be made of TPU.

[0021] The first substrate part 110 in this example has a first fluid channel 111 and a second fluid channel 112, which are separated from each other by the valve seat 115. According to a first step 501 of the manufacturing method 500, the first substrate part 110 is thus provided as a valve body with a valve seat 115 and fluid channels 111, 112. For example, the two fluid channels 111, 112 can be formed by two spaced-apart recesses, in particular bores or milled recesses or as a molding in injection molding, in the first substrate part, wherein the recesses simultaneously create the valve seat 115. The valve seat 115 has a height such that the membrane 130 in the region of the valve seat, as in Fig.2 (even at rest) and thus preferably prestressed. For example, the two substrate parts 110, 120 have a thickness between 100 µm (micrometers) and 10 mm (millimeters). The membrane can, for example, have a thickness between 10 µm and 1 mm. The fluid channels 111, 112 have cross-sections in the range between 0.1 and 10 mm. 2The valve seat 115 can, for example, have a width between 100 µm and 5 mm and a height between 100 µm and 5 mm. Preferably, the height of the valve seat 115 is configured such that it protrudes between 5 µm and 1 mm beyond the first substrate part toward the membrane 130. In other words, the first substrate part 110, at the location of the valve seat, together with the valve seat, preferably has a width (as the sum of the thickness referred to above and the protruding part of the valve seat) between 105 µm and 11 mm, and otherwise preferably has a width, referred to above as thickness, between 100 µm and 10 mm.

[0022] In a second step 502, the membrane 130 is arranged relative to the valve body 110 such that an expandable part of the membrane 130 in the region of the valve seat 115 is stretched by the valve seat and thus prestressed. This arrangement 502 can be achieved, in particular, by a sandwich-like arrangement of the membrane 130 between the two substrate parts 110, 120. In particular, the membrane 130 can be connected to the two substrate parts 110, 120 by laser transmission welding if the two substrate parts 110, 120 are sufficiently transparent at least in some areas.

[0023] The second substrate part 120 has a third fluid channel 113, which opens at the side 132 of the membrane 130 facing away from the valve seat, for example in the form of a, for example, conical, widening, so that when a sufficiently high negative pressure is applied, the membrane in the region of the valve seat 115 is stretched even more in the direction of the third channel 113, a fluidic connection is created between the first and second fluid channels 111, 112 via the resulting distance between the valve seat 115 and the side 131 of the membrane 130 facing the valve seat 115 in the first substrate part 110 and the valve 100 can thus be switched from the closed rest state to the actuated open state.

[0024] The part 140 of the valve seat 115 that contacts and prestresses the diaphragm 130 can, according to a particular embodiment, have a particular shape and / or surface finish. For example, the surface of the part 140 that contacts the diaphragm can be smooth at least in some areas and / or have predetermined structures to ensure strong adhesion of the diaphragm 130 to the valve seat 115. Furthermore, the part 140 can have rounded edges 141, 142, in particular along the edge of the valve seat 115 that is contacted by the diaphragm 130, so that the side 131 of the diaphragm 103 facing the valve seat 115 can conform to the valve seat 115 without any edges. The rounding of the edges 141, 142 can be realized in the form of a convex formation of the surface of the valve seat 115, which in the closed state touches the facing side 131 of the membrane 103.In other words, this surface has an arcuate shape, particularly in cross-section, wherein the arc bulges out as a convex formation of the surface of the valve seat 115 towards the facing side 131 of the membrane 103.

[0025] This part 140 of the valve seat 115 that contacts the diaphragm 130 can, according to a special embodiment, be formed as a separate part 140, which is connected to a base 116 of the valve seat 115 and, together with the base 116, forms the valve seat 115. For example, the part 140 can be designed as a coating. The part 140 can also be formed as a separate component as an attachment for the valve seat, which allows for separate production and / or material composition from the rest of the diaphragm valve 100. The component 140 can also consist of or comprise a polymer, for example, an elastomer or a hydrophobic polymer. For example, the component 140 is also injection-molded and is subsequently glued or welded to the base 116 of the valve seat, for example, by laser transmission welding.Alternatively, the component 140 is manufactured in a single production step with the base stock 116, for example, by two-component injection molding. However, the component 140 can also consist of or comprise other materials, such as metal, silicon, or ceramic, in order to achieve the smoothest possible surface. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] US 7 607 641 B1

[0002] US 2023 / 0226547 A1

[0002]

Claims

[1] Microfluidic membrane valve (100), in particular for a microfluidic cartridge (200) for the detection of pathogens, wherein the membrane valve (100) is closed by at least partial contact of a membrane (130) with a valve seat (115), wherein the membrane (130) is stretched, in particular prestressed, by the valve seat (115) in the rest state. [2] Microfluidic diaphragm valve (100) according to claim 1, wherein the valve seat (115) has such a height that the diaphragm (130) which is fixedly arranged in the diaphragm valve (100) is stretched by the valve seat (115) and thus preferably pre-tensioned. [3] Microfluidic diaphragm valve (100) according to one of the preceding claims, wherein the diaphragm valve (100) comprises three parts (110, 120, 130), wherein a first part has a valve body with the valve seat (115), and wherein the diaphragm (130) is arranged as a third part (130) between the first part (110) and a second part (120) and is in particular clamped, and wherein the second part (120) preferably has a channel (113) for actuating the diaphragm valve (100) by applying negative or positive pressure to the diaphragm (130) in a region of the valve seat (115). [4] Microfluidic membrane valve (100) according to claim 3, wherein the first part (110) and the second part (120) form parts in two, in particular parallel, layers. [5] Microfluidic diaphragm valve (100) according to one of the preceding claims, wherein a surface of the valve seat (115) facing the diaphragm (130) is convex in certain areas, in particular to round off an edge of the valve seat (115). [6] Microfluidic diaphragm valve (100) according to one of the preceding claims, wherein a part (140) of the valve seat (115) facing the diaphragm (130) has a different material composition than a remainder (116) of the valve seat (115) or the part (140) is preferably designed as a separate component. [7] Microfluidic diaphragm valve (100) according to one of the preceding claims, wherein a region of the valve seat (115) which in the closed state contacts the diaphragm (130) has a coating for adhesion of the diaphragm (130). [8] Microfluidic diaphragm valve (100) according to one of the preceding claims, wherein the diaphragm (130) is detachably connected to the valve seat (115) at least partially, in particular by a material-bonded connection. [9] Microfluidic cartridge (200), in particular for the detection of pathogens, comprising a microfluidic membrane valve (100) according to any of the preceding claims. [10] Microfluidic cartridge (200) according to claim 9, wherein the cartridge (200) has a first layer (110), a second layer (120) and a cartridge membrane (130) arranged between the two layers (110, 120), wherein the membrane valve (100) is formed by recesses in the two layers and wherein the cartridge (200) membrane (130) in the region of the membrane valve (100) forms the membrane (130) of the membrane valve (100). [11] Method (500) for manufacturing a microfluidic diaphragm valve (100) according to any one of claims 1 to 8, comprising the steps: • Providing (501) a valve body (110) with a valve seat (115), wherein the valve seat (115) may be formed by a recess in the valve body, and a diaphragm that is at least partially extensible. • Arranging the diaphragm (130) in such a way as to the valve body (110) that a stretchable area of ​​the diaphragm (130) is stretched by the valve seat (115) and thus preferably pre-tensioned. [12] Method (502) according to claim 11, wherein a part (140) of the valve seat (115) contacting the diaphragm (130) is manufactured separately, wherein the part (140) is connected to a base (116) of the valve seat (115).

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