Microfluidic device and method for its manufacture

Abstract

The invention relates to a microfluidic device (10) comprising a pneumatic layer (11), a fluidic layer (12), and a membrane (13) which is partially arranged between the pneumatic layer (11) and the fluidic layer (12), wherein at least one component (22) is arranged in one of the two layers (11, 12), in particular in the pneumatic layer (11). The component (22) is arranged in at least one guide rail (21).A method for manufacturing the microfluidic device (10) comprises manufacturing at least one guide rail (21) from a first material, arranging the at least one guide rail (21) and at least one component (22) in an injection molding tool, overmolding the guide rail (21) and the component (22) with a second material to obtain a layer (11, 12), in particular a pneumatic layer (11), and joining the layer (11, 12), in particular the pneumatic layer (11), with a membrane (12) and a second layer (12, 11), in particular a fluidic layer (13), to obtain the microfluidic device (10).

Description

[0001] The present invention relates to a microfluidic device. Furthermore, the present invention relates to a method for producing the microfluidic device. State of the art

[0002] Microfluidic cartridges, also known as lab-on-chip cartridges, are used in microfluidic analysis systems for analyzing body fluids and for real-time diagnostics in doctor's offices and hospitals. Such microfluidic cartridges feature a microcavity array in which a sample is reacted with various reagents. The array chamber, in which the microcavity array is arranged, has a window that allows optical evaluation of the reactions, for example, through fluorescence spectroscopy.

[0003] DE 10 2020 210 276 A1 discloses a microfluidic cartridge consisting of multiple plastic layers. A microcavity array is arranged in an array chamber extending across multiple layers. The microcavity array is glued into one of the layers. Disclosure of the invention

[0004] The microfluidic device comprises a pneumatic layer, a fluidic layer, and a membrane partially arranged between the pneumatic layer and the fluidic layer. A fluidic layer is a layer having chambers and channels configured to transport a sample and react it with reagents. A pneumatic layer is a layer having channels that border the membrane at one end and can be connected to a pneumatic manifold at the other end. By generating positive pressure in the channels of the pneumatic layer, the membrane can be deflected into the fluidic layer, and by generating negative pressure in the channels of the pneumatic layer, the membrane can be forced into the pneumatic layer. This makes it possible to manipulate fluid flows in the fluidic layer.The material of the fluidic layer and pneumatic layer is preferably a plastic, which makes these layers easy to manufacture. A particularly preferred plastic is polycarbonate (PC), which is transparent and allows the components of the microfluidic device to be joined together by laser welding. Another particularly preferred plastic is styrene acrylonitrile (SAN). This does not have as good optical properties as polycarbonate, but is more cost-effective. Both polycarbonate and styrene acrylonitrile can be laser-welded to the membrane. They are also resistant to the temperatures typically encountered during operation of the microfluidic device. The membrane is preferably made of thermoplastic polyurethane (TPU). This is particularly well-suited for the membrane due to its high elasticity.Due to its thermoplasticity, it can also be laser welded with polycarbonate and styrene acrylonitrile.

[0005] In particular, the microfluidic device is designed as a disposable cartridge intended to be used in a microfluidic analysis system.

[0006] At least one component is arranged in one of the two layers, the pneumatic layer or the fluidic layer. While it is fundamentally possible to glue components into a microfluidic device, in the present case it is provided that the component is arranged in at least one guide rail. This avoids misalignments of the component, which can occur with glued components due to inaccurate dosing of the adhesive or the adhesive running. A guide rail is understood to be an element into which the component can be inserted such that it is fixed in a defined position with respect to at least one, preferably two spatial directions. The guide rail can in particular have a groove-shaped recess for receiving a part of the component.

[0007] The guide rail is preferably positively connected to a material of the layer, in particular the pneumatic layer. Such a positive connection can be achieved in particular by overmolding the guide rail with the material of the layer. In a preferred embodiment, the connection to this is also materially bonded, in that the guide rail is made of the same material as the layer. However, in another preferred embodiment, it can also be provided that the layer is made of a less expensive material than the guide rail. For example, the guide rail can be made of polycarbonate and the layer of styrene acrylonitrile.

[0008] The component arranged in the guide rail is, in particular, a microcavity array. In microfluidic devices, microcavity arrays are flooded with a sample fluid. It must be ensured, on the one hand, that each cavity is filled with the sample fluid, and, on the other hand, that reagents stored in the microcavities are not flushed out of the cavities by the sample fluid. Therefore, microcavity arrays are components whose positioning in a microfluidic device must be particularly precise. The microcavity array can, in particular, comprise a silicon substrate in which cavities are formed. Its thickness is, in particular, in the range of 100 µm to 600 µm. The diameter of the microcavities is preferably in the range of 10 µm to 1,000 µm, and particularly preferably in the range of 100 µm to 400 µm.This ensures, on the one hand, that the cavities can be easily filled and, on the other hand, that a sufficiently large number of cavities can be arranged on the substrate. The depth of the microcavities is preferably in the range of 100 µm to 700 µm, particularly preferably in the range of 200 µm to 300 µm. This ensures, on the one hand, a sufficient volume of the cavities and, on the other hand, prevents an excessive portion of the substrate's material thickness from being removed.

[0009] If the component is a microcavity array, it is preferably arranged in an array chamber in the layer, in particular the pneumatic layer. This array chamber is at least partially, preferably completely, bounded by the guide rail.

[0010] Preferably, no adhesive is placed in the array chamber. Using the guide rail eliminates the need for this. This eliminates the risk of components detaching from the adhesive during curing and depositing as a coating on the microcavity array or on an optical element of the array chamber.

[0011] Preferably, such an optical element is arranged at an end of the array chamber facing away from the component. The optical element is, in particular, a transparent window, which is preferably configured to perform an optical examination of the contents of the cavities of the microcavity array from a side of the fluidic layer facing away from the pneumatic layer.

[0012] The optical element is preferably arranged in a plane of the membrane. For this purpose, the membrane is perforated in the area of ​​the array chamber so that it does not interrupt the light path through the optical element into the array chamber.

[0013] The optical element is preferably formed integrally with the guide rail. This allows the guide rail to form a media-tight boundary around the array chamber not only at its side walls, but also at its top, i.e., the side facing away from the microcavity array. Furthermore, the optical element can be inserted into the microfluidic device together with the guide rail and always assumes a defined position relative to the guide rail and thus also relative to the microcavity array.

[0014] The height of the guide rail preferably corresponds to the sum of the thickness of the layer, in particular the pneumatic layer, and the thickness of the membrane. If the optical element is arranged in the plane of the membrane and is formed integrally with the guide rail, this means that the guide rail extends through the entire pneumatic layer and through the membrane layer.

[0015] The method for producing the microfluidic device comprises producing a guide rail from a first material. This production takes place in particular using an injection molding process. The at least one guide rail and the at least one component are arranged in an injection molding tool. Subsequently, the guide rail and the component are encapsulated with a second material in order to obtain a layer, in particular a pneumatic layer. The first material and the second material can be identical or different in different embodiments of the method. Finally, the layer, in particular the pneumatic layer, is joined to a membrane and a second layer, in particular a fluidic layer, in order to obtain the microfluidic device. The joining can take place in particular by laser welding.

[0016] Preferably, an optical element is arranged in the injection molding tool at the same time as the guide rail is arranged.

[0017] For this purpose, it is further preferred that the optical element is made in one piece with the guide rail from the first material.

[0018] Such a process makes it possible to manufacture the microfluidic device with few process steps, few sources of error and little time expenditure. Short description of the drawings

[0019] Embodiments of the invention are illustrated in the drawings and are explained in more detail in the following description. Fig. 1 shows a cross-sectional view of a microfluidic device according to an embodiment of the invention. Fig. 2 shows a flowchart of a method according to an embodiment of the invention. Fig. 3 shows a cross-sectional view of a first injection molding tool in a step of an embodiment of the method according to the invention. Fig. 4 shows a cross-sectional view of a second injection molding tool in a step of an embodiment of the method according to the invention. Fig. 5 shows a cross-sectional view of the second injection molding tool in another step of an embodiment of the method according to the invention. Embodiments of the invention

[0020] In an embodiment of the microfluidic device 10, which is shown in Fig. 1, this is designed as a microfluidic cartridge. This has a pneumatic layer 11 and a fluidic layer 12, each made of styrene acrylonitrile, for example. A membrane 13, made of thermoplastic polyurethane, for example, is arranged between the pneumatic layer 11 and the fluidic layer 12. It is laser-welded to the pneumatic layer 11 and the fluidic layer 12. The fluidic layer 12 has an opening 14 above an array chamber 20. This array chamber 20 is arranged in the pneumatic layer 11. Its side walls are delimited by a guide rail 21, made of polycarbonate, for example. The guide rail 21 extends over the entire height of the pneumatic layer 11 and over the height of the membrane 13, which is perforated in the region of the opening 14.Near the side of the array chamber 20 facing away from the opening 14, a component 22 in the form of a microcavity array is fixed in the guide rail 21, in particular, as indicated, in a groove-shaped recess of the guide rail 21. This component is made of silicon, for example, and has microcavities in which dried reagents are stored. An optical element 23 in the form of a window is formed integrally with the guide rail 21 and has the same thickness as the membrane 13. It is arranged in the plane of the membrane 13 between the pneumatic layer 11 and the fluidic layer 12. The guide rail 21 is toothed on its outer sides and engages positively with the material of the pneumatic layer 11. A microfluidic channel of the fluidic layer 12 opens into the array chamber 20. It allows a sample liquid to be introduced into the array chamber 20 so that it floods the component 22.Another microfluidic channel, the fluidic layer 12, also opens into the array chamber 20 as an outlet and pressure equalization. If this microfluidic device 10 is used in a microfluidic analysis system, a sample fluid can be transported through the fluidic layer 12 and then flow into the array chamber 20 in the pneumatic layer 11. There, it reacts with the reagents stored in the cavities of the component 22. The reaction products can be examined by fluorescence spectroscopy through the opening 14 and the optical element 23.

[0021] The sequence of a method for producing such a microfluidic device 10 in an embodiment of the invention is shown in Fig. 2. After the start 30 of the process, the guide rail 21 and the optical element 23 are first manufactured 31 using a slide molding technique. This manufacturing takes place in a first injection molding tool 40, which is Fig. 3. The first injection mold 40 has a nozzle side 41 and an ejector side 42. In the nozzle side 41, a rod gate 43 with a sub-distributor is arranged, through which molten polycarbonate (for example, Makrolon ® from Covestro AG, Germany) as the first material 51 into the nozzle side 41. There, two guide rails 21 are formed integrally with an optical element 23 by means of stamps 44. A toothed structure of the outer side of the guide rails is predetermined by the shape of the cavities into which the first material 51 is introduced. Slides 45 serve to form recesses in the inner walls of the guide rails 21, which are later intended to accommodate the component 22 and whose height corresponds to the thickness of the component 22.

[0022] After the guide rail 21 and the optical element 23 have been produced, an arrangement 32 of these elements takes place together with the microcavity array as a component 22, which has been pushed into the recesses on the inside of the guide rail 23, in a second injection molding tool 60. This is shown in Fig. 4. The second injection molding tool 60 has a nozzle side 61 and an ejector side 62. A hot runner 63 with a needle valve is arranged in the nozzle side. This opens into a cavity 64, which serves to form the pneumatic layer 11. The guide rail 21, the component 22, and the optical element 23 are inserted into this cavity 64. They are fixed between a punch 65 arranged in the nozzle side, which is provided with grooves and has a wedge-shaped positioning stop 66, and an insert 67 in the ejector side provided with fixing pins. The positioning stop engages the component 22. In addition, the optical element 23 is held to the insert 67 by means of a vacuum 68, which also ensures the defined positioning of the guide rail 21 and the component 22. The fixing pins define the inlet and outlet of the array chamber 20.

[0023] This is followed by overmolding 33 of the guide rail 21 and the component 22 with styrene acrylonitrile (for example Luran ® of INEOS Styrolution Group GmbH, Germany) as the second material 52, which is introduced into the cavity 64 through the hot runner 63 and can flow through the grooves of the punch 65. This forms the pneumatic layer 11. The guide rail 21 is positively fixed in the pneumatic layer 11. Since the array chamber 20 is delimited laterally by the guide rail 21, on its underside by the component 22, and on its upper side by the optical element and the insert 67, it is not filled with the second material 52, but rather sealed by it.

[0024] In another embodiment, the same material that was used as the first material 51 is used as the second material 51.

[0025] After the pneumatic layer 11 has been removed from the second injection mold 60, it is joined 43 to a fluidic layer 12 and a membrane 13. For this purpose, the membrane 13 is first placed on the pneumatic layer 11 and laser-welded to it. The membrane 13 has an opening in the region of the optical element 23. This extends beyond the upper side of the pneumatic layer, which faces the membrane 13, and lies in the plane of the membrane 13. Subsequently, the fluidic layer 12 is placed on the membrane 13 and also laser-welded to it. The fluidic layer 12 has an opening 14, which is arranged above the optical element 23. In this way, the microfluidic device 10 according to Fig. 1 is received and the procedure is terminated 35. 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] DE 10 2020 210 276 A1

[0003]

Claims

[1] Microfluidic device (10), comprising a pneumatic layer (11), a fluidic layer (12) and a membrane (13) which is partially arranged between the pneumatic layer (11) and the fluidic layer (12), wherein at least one component (22) is arranged in one of the two layers (11, 12), in particular in the pneumatic layer (11), characterized by that the component (22) is arranged in at least one guide rail (21). [2] Microfluidic device (10) according to claim 1, characterized by that the guide rail (21) is positively connected to a material of the layer (11, 12), in particular the pneumatic layer (11). [3] Microfluidic device according to claim 1 or 2, characterized by that the component (22) is a microcavity array. [4] Microfluidic device according to claim 3, characterized bythat the component (22) is arranged in an array chamber (20) of the layer (11, 12), in particular in the pneumatic layer (11). [5] Microfluidic device (10) according to claim 4, characterized by that no adhesive is arranged in the array chamber (20). [6] Microfluidic device (10) according to claim 4 or 5, characterized by that an optical element (23) is arranged at an end of the array chamber (20) facing away from the component (22). [7] Microfluidic device (10) according to claim 6, characterized by that the optical element (23) is arranged in a plane of the membrane (13). [8] Microfluidic device (10) according to claim 6 or 7, characterized by that the optical element (23) is formed integrally with the guide rail (21). [9] Microfluidic device according to one of claims 4 to 8, characterized bythat a height of the guide rail (21) corresponds to a sum of a thickness of the layer (11, 12), in particular the pneumatic layer (11) and a thickness of the membrane (13). [10] A method for producing a microfluidic device (10) according to any one of claims 1 to 9, comprising the following steps: - producing (31) at least one guide rail (21) from a first material (51), - arranging (32) the at least one guide rail (21) and at least one component (22) in an injection molding tool (60), - overmolding (33) the guide rail (21) and the component (22) with a second material (52) in order to obtain a layer (11, 12), in particular a pneumatic layer (11), and - joining (34) the layer (11, 12), in particular the pneumatic layer (11) with a membrane (12) and a second layer (12, 11), in particular a fluidic layer (13), in order to obtain the microfluidic device (10). [11] Method according to claim 10, characterized by that an optical element (23) is arranged in the injection molding tool (60) at the same time as the guide rail is arranged (32). [12] Method according to claim 10 or 11, characterized by that the optical element (23) is made in one piece with the guide rail (21) from the first material (51).

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