Microfluidic device and method for producing and operating same
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2026-01-27
- Publication Date
- 2026-08-13
Smart Images
Figure EP2026051961_13082026_PF_FP_ABST
Abstract
Description
[0001] R. 416207
[0002] - 1 -
[0003] Description
[0004] title
[0005] Microfluidic device and methods for its manufacture and operation
[0006] The present invention relates to a method for manufacturing a microfluidic device. Furthermore, the present invention relates to a microfluidic device that can be manufactured, in particular, by means of the method. Finally, the present invention relates to a method for operating the microfluidic device.
[0007] State of the art
[0008] In microfluidic analysis systems, biological samples can be reacted with pre-treatment reagents to determine the sample composition. These reagents are often stored in freeze-dried or lyophilized form. Enzymes, for example, can be stored in this form without refrigeration. Freeze-dried reagents in spherical or tablet form can be enclosed in a chamber of a disposable microfluidic cartridge.
[0009] DE 102018204633 A1 describes a microfluidic device for processing a liquid in which a dry reagent in the form of a so-called bead is placed upstream. This is dissolved by the targeted generation of turbulent flows in a liquid. R. 416207
[0010] - 2 -
[0011] Disclosure of the invention
[0012] The method serves to manufacture a microfluidic device, in particular a microfluidic cartridge, which has several microfluidic layers. A microfluidic layer is understood to be a layer in which microfluidic chambers and / or channels are arranged. First, a first microfluidic layer is provided, which has a first chamber section. A channel for applying a vacuum, hereinafter referred to as the vacuum channel, opens into this first chamber section. The vacuum channel is configured to generate a vacuum within it. A solid reagent is placed in the first chamber section. This solid reagent is, in particular, a freeze-dried reagent, which may, for example, be in spherical or tablet form. By applying a vacuum to the vacuum channel, the reagent is fixed in place.
[0013] Here, the solid reagent is drawn into the opening of the vacuum channel in the first chamber section. Therefore, the dimensions of the solid reagent must be larger than the opening of the vacuum channel into the first chamber section to prevent it from being drawn into the vacuum channel. This fixation of the reagent has the advantage of holding it in a defined position within the first chamber section, preventing it from jumping out of position, even if the first microfluidic layer is moved later in the process. After the reagent is fixed, a second microfluidic layer is applied on top of the first. This transforms the first chamber section into a chamber within the microfluidic device. The reagent is then enclosed within this chamber.In further steps of the process, the two microfluidic layers can be permanently joined together, for example by welding. For this purpose, they preferably consist of a thermoplastic polymer, such as polycarbonate.
[0014] In principle, the chamber can be formed by the second microfluidic layer simply covering and thus sealing the first chamber part. The second microfluidic layer can be made very thin. In particular, the second microfluidic layer exhibits a [R. 416207].
[0015] - 3 -
[0016] second chamber part. In this embodiment of the method, it is arranged on the first microfluidic layer in such a way that the two chamber parts together form a chamber in the microfluidic device.
[0017] This method has the advantage of simplifying the fabrication of the microfluidic device because the two microfluidic layers can be merged without the risk of the reagent detaching from the first chamber section before merging. A constant negative pressure in the vacuum channel indicates that the reagent has been successfully immobilized. Therefore, quality control after merging the microfluidic layers is unnecessary, as it would otherwise be required, for example, by optical inspection through a transparent material of the microfluidic layers to verify that the reagent has indeed been contained within the chamber.
[0018] The following describes various preferred embodiments of the method:
[0019] In a preferred embodiment, the first chamber section is open on two opposite sides of the first microfluidic layer. Such a breakthrough through the first microfluidic layer is particularly easy to manufacture. The opening facing away from the second microfluidic layer is then closed by means of a cover film. This cover film can, in particular, consist of a polymer that is welded or fused to the first microfluidic layer. Preferably, this polymer is polycarbonate. However, it is also conceivable to adhere the cover film to the first microfluidic layer. In this embodiment, the vacuum channel preferably opens laterally into the first chamber section. Particularly preferably, it opens into the first chamber section at the bottom formed by the cover films, with the vacuum channel, for example, running parallel to one of the cover films in the area in front of the opening.This enables efficient fixation of the reagent. R. 416207.
[0020] - 4 -
[0021] In another preferred embodiment of the method, the vacuum channel opens into the first chamber part on the side facing away from the second microfluidic layer. Particularly preferably, the vacuum channel opens into the first chamber part through a sieve structure. This sieve structure can be realized, in particular, by a plurality of perforations. Other possibilities for realization include the insertion of a porous insert, such as a plastic frit, into the first chamber part, or the insertion of a water-impermeable membrane into the first chamber part. The use of the sieve structure has the advantage that the settling area of the reagent is increased, and thus, in particular, non-spherical reagents can also be reliably fixed.
[0022] The chamber has, in particular, at least one feed channel for supplying a liquid in which the reagent is to be dissolved. It also has, in particular, at least one discharge channel for removing a fluid. A discharge channel can, in particular, serve as a venting channel or be designed to convey a liquid in which the reagent has been dissolved into another chamber of the microfluidic device. Preferably, a feed channel or a discharge channel of the chamber opens into the vacuum channel. While the vacuum channel is used during the manufacture of the microfluidic device to fix the reagent by means of a vacuum, it can serve during operation of the microfluidic device for supplying or removing a fluid.
[0023] In one embodiment of the method, the vacuum channel remains open after the second microfluidic layer is applied, allowing it to be used as a feed or discharge channel during operation of the microfluidic device itself. In another preferred embodiment, the vacuum channel is closed after the second microfluidic layer is applied. If a feed or discharge channel of the chamber opens into the vacuum channel, this closure, viewed from the chamber, occurs beyond the opening point, thus preventing any supplied or discharged fluid from unintentionally entering the vacuum channel. R. 416207
[0024] - 5 -
[0025] The vacuum channel can be sealed, for example, by means of a rotary valve, a sticker, or by inserting a plug. However, some embodiments of the method also allow the vacuum channel to be sealed simply using a molten plastic.
[0026] In a preferred embodiment of the method, the vacuum channel is open to the side of the first microfluidic layer facing away from the second microfluidic layer. Its open area is covered by a cover film, and the sealing is achieved by melting the cover film so that its molten material penetrates the vacuum channel.
[0027] In another preferred embodiment of the method, the vacuum channel is open to the side of the first microfluidic layer facing the second microfluidic layer. Its open area is covered by a connecting film placed between the first and second microfluidic layers. The sealing is achieved by melting the connecting film so that its molten material penetrates the vacuum channel. In this embodiment, the connecting film also serves to permanently bond the two microfluidic layers together. In particular, the connecting film is made of polycarbonate.
[0028] A microfluidic device with two interconnected microfluidic layers and a chamber that, in one embodiment, extends into both microfluidic layers, can be produced, in particular, by the method described above. A reagent is arranged in the chamber, and a vacuum channel opens into the chamber. In particular, the microfluidic device is a microfluidic cartridge.
[0029] If the device was manufactured using an embodiment of the method in which the vacuum channel was not closed after the arrangement of the second microfluidic layer, the microfluidic device can be operated in such a way that the vacuum channel is used to supply a R. 416207
[0030] - 6 -
[0031] Fluids, in particular a liquid, into the chamber or for the removal of a fluid, in particular a liquid, from the chamber.
[0032] Brief description of the drawings
[0033] Exemplary embodiments of the invention are shown in the drawings and are explained in more detail in the following description.
[0034] Figure 1 schematically shows a chamber in a microfluidic device according to an embodiment of the invention.
[0035] Figure 2 schematically shows a chamber in a microfluidic device according to another embodiment of the invention.
[0036] Figure 3 shows in a schematic sectional view components of a microfluidic device which are assembled in a method according to an embodiment of the invention.
[0037] Figure 4 shows a flowchart of a method according to an embodiment of the invention.
[0038] Figure 5 shows in a schematic sectional view components of a microfluidic device which are assembled in another embodiment of the method according to the invention.
[0039] Figure 6 shows a flowchart of another embodiment of the method according to the invention.
[0040] Figure 7 shows in a schematic sectional view components of a microfluidic device which are assembled in yet another embodiment of the method according to the invention.
[0041] Figure 8 shows a flowchart of yet another embodiment of the method according to the invention. R. 416207
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[0043] Figure 9 schematically shows a chamber in a microfluidic device according to yet another embodiment of the invention.
[0044] Figure 10 shows a schematic cross-sectional view of a microfluidic layer, which is used in yet another embodiment of the method according to the invention.
[0045] Figure 11 shows a flowchart of yet another embodiment of the method according to the invention.
[0046] Figure 12 shows a schematic representation of a chamber in a microfluidic device according to yet another embodiment of the method according to the invention.
[0047] Figure 13 shows a schematic sectional view of a microfluidic layer used in yet another embodiment of the method according to the invention.
[0048] Figure 14 shows a flowchart of yet another embodiment of the method according to the invention.
[0049] Exemplary embodiments of the invention
[0050] In a first embodiment of the method according to the invention, a microfluidic device can be manufactured comprising a chamber 10, as shown in Figure 1. A vacuum channel 11, a feed channel 12, and a discharge channel 13 open into this chamber 10. The channels 11, 12, and 13, in particular the vacuum channel 11, can, for example, have a diameter between 200 micrometers (pm) and 1 millimeter (mm), for example, 600 pm. The vacuum channel 11 can, in particular, widen before opening into the chamber, for example, conically, for example, to a diameter of 2 mm. A solid reagent 20 is arranged in the chamber 10 and can be fixed at the opening of the vacuum channel 11 during the manufacture of the microfluidic device by applying a vacuum to it. The reagent 20 can, for example, be a
[0051] - 8 -
[0052] They must have a width or diameter between 500 pm and 5 mm, for example 3 mm, and in particular be spherical in shape. The applied vacuum can be, for example, between 100 millibar (mbar) and 1.5 bar, for example 500 mbar.
[0053] Using the same embodiment of the method according to the invention, a microfluidic device can also be produced, the chamber 10 of which is shown in Figure 2. This differs from the microfluidic device according to Figure 1 in that the feed channel 12 does not open into the chamber 10, but instead into the vacuum channel 11.
[0054] The components used in the first embodiment of the method according to the invention are shown in Figure 3, and the process of this embodiment is shown in Figure 4. A first microfluidic layer 30, which consists, for example, of polycarbonate, has a first chamber part 31. A second microfluidic layer 40 also consists, for example, of polycarbonate. A vacuum channel 11 extends from the first chamber part 31 to the opposite side of the first microfluidic layer 30.
[0055] After the process is started 60, the first microfluidic layer 30 is first provided 61. The solid reagent 20 is then placed in the first chamber section 31 64. A vacuum source (not shown) is used to create a vacuum in the vacuum channel 11, thus fixing the reagent 20 at the opening of the vacuum channel 11 into the first chamber section 31 65. The second microfluidic layer 40 is then provided 66. It is placed on top of the first microfluidic layer 30 67 so that it covers the first chamber section 31, forming the chamber 10 in which the reagent 20 is enclosed. The two microfluidic layers 30 and 40 are then firmly bonded together, for example, by laser transmission welding. Finally, the vacuum channel 11 is closed 68 by inserting a plug 32 into it. After the vacuum channel 11 is closed, the process 69 is terminated.
[0056] Manufacturing process. R. 416207
[0057] - 9 -
[0058] The components used in the second embodiment of the method according to the invention are shown in Figure 5, and the process of this embodiment is shown in Figure 6. In this embodiment of the method, microfluidic devices with chambers 10, as shown in Figures 1 and 2, can also be produced. A first microfluidic layer 30, which is made, for example, of polycarbonate, has a first chamber part 31. A second microfluidic layer 40, which is also made, for example, of polycarbonate, has a second chamber part 41. A cover film 50, which is also made, for example, of polycarbonate, can be arranged on the side of the first microfluidic layer 30 facing away from the first chamber part 31 such that it covers an open area of the vacuum channel 11.This extends from the first chamber section 31 to the opposite side of the first microfluidic layer 30 and then bends at a right angle. It is open on this side.
[0059] After the start 60 of the process, the first microfluidic layer 30 is first provided 61. Then the cover film 50 is provided 62. The side of the first microfluidic layer facing away from the first chamber part 31 is covered with the cover film 50, 63, and this is fused with the first microfluidic layer 30 in such a way that the outwardly open area of the vacuum channel 11 is hermetically sealed. The solid reagent 20 is now arranged in the first chamber part 31 64. A vacuum source (not shown) is used to create a vacuum in the vacuum channel 11, thus fixing the reagent 20 at the opening of the vacuum channel 11 in the first chamber part 31 65. The second microfluidic layer 40 is then provided 66. This layer is arranged on top of the first microfluidic layer 30 67 such that the two chamber parts 31, 41 together form the chamber 10 in which the reagent 20 is enclosed.The two microfluidic layers 30, 40 are firmly bonded together, for example, by laser transmission welding. Finally, the vacuum channel 11 is sealed 68 by locally heating the cover film 50 or the first microfluidic layer 30 again so that it melts locally and its molten material penetrates the vacuum channel 11, where it forms a seal 51. After the vacuum channel 11 is sealed, the process 69 is terminated.
[0060] Manufacturing process. R. 416207
[0061] - 10 -
[0062] In a third embodiment of the method according to the invention, microfluidic devices with chambers 10, as shown in Figures 1 and 2, can also be produced. The components used here are shown in Figure 7, and the process sequence is shown in Figure 8. The components differ from those used in the second embodiment in that the vacuum channel 11, after its initial right-angle bend, does not run parallel to the side of the first microfluidic layer 30 facing away from the first chamber part 31 along its entire remaining length. Instead, it bends again at a right angle and is guided back to the opposite side of the first microfluidic layer 30, where it bends one last time and then runs along this side. It is open towards this side.In this third embodiment of the method, the use of a connecting film 70, made of polycarbonate for example, is further provided. It has the same length and width dimensions as the two microfluidic layers 30, 40, but is perforated in the area of the two chamber parts 31, 41.
[0063] After the start 60 of the process, the same process steps 61 to 63 are carried out as in the second embodiment. Immediately before the arrangement 64 of the reagent 20, the connecting foil 70 is provided 81, positioned on the side of the first microfluidic layer 30 having the first chamber part 31, and thermally or via laser radiation welded to it 82 such that it closes the area of the vacuum channel 11 open on this side of the first microfluidic layer 30. Alternatively, process steps 81 and 82 can also take place before process steps 62 and 63. Subsequently, process steps 64 to 66 are carried out as in the second embodiment of the process.Instead of placing the second microfluidic layer 40 directly onto the first microfluidic layer 30 in process step 67, in this embodiment of the process it is placed indirectly onto the first microfluidic layer 30 via the connecting film 70 83. It is fused with this layer so that the first microfluidic layer 30 can no longer be separated from the second microfluidic layer 40. The vacuum channel 11 is sealed by R. 416207.
[0064] - 11 -
[0065] The connecting foil 70 is then locally heated again by means of laser transmission welding to such an extent that it melts at a specific point and its molten material penetrates the vacuum channel, where it forms a seal 71. The process for manufacturing the device is then terminated 85.
[0066] In a fourth embodiment of the method according to the invention, a microfluidic device can be manufactured, the chamber 10 of which is shown in Figure 9. It has only a vacuum channel 11 and a discharge channel 13. A separate feed channel 12 can be omitted, since the vacuum channel 11 is not closed in this embodiment and can function as a feed channel during operation of the microfluidic device.
[0067] Figure 10 shows the components used in this embodiment of the method according to the invention, which differ from the components of the third embodiment. The second microfluidic layer 40 and the connecting film 70 are designed in the same way as in the third embodiment and are therefore not shown again. The vacuum channel 11 opens into the first chamber part 31 at the bottom through a sieve structure 33, which is designed, for example, as an insert. It then initially proceeds as in the third embodiment, but finally bends at a right angle and runs one last time through the entire thickness of the first microfluidic layer 30 until it opens at the side of the first microfluidic layer 30 facing away from the first chamber part 31. At this point, an opening 52 is provided in the cover film 50 through which the vacuum channel 11 is accessible.
[0068] The procedure corresponds to the procedure of the third embodiment, with the difference that the sealing 84 of the vacuum channel 11 is omitted. During operation of the resulting microfluidic device, a liquid can be introduced through the opening 52 in the cover film 50, which flows uniformly from below through the sieve structure 33 onto the reagent 20. The dissolved reagent 20 can then be flushed out of the chamber 10 through the discharge channel 13. R. 416207
[0069] - 12 -
[0070] A fifth embodiment of the method according to the invention enables the fabrication of a microfluidic device with a chamber 10, which is shown in Figure 12. As in the fourth embodiment, a feed channel 12 is omitted. However, the vacuum channel 11 runs parallel to the bottom of the chamber 10. Figure 11 shows components used in this embodiment of the method according to the invention. Furthermore, a second microfluidic layer 40 is used, as shown in Figure 3. The first chamber part 31 in the first microfluidic layer 30 has no bottom. Instead, the first chamber part 31 extends through the entire thickness of the first microfluidic layer 30. The vacuum channel 11 opens laterally into the first chamber part 31.
[0071] The sequence of this embodiment of the method according to the invention is illustrated in Figure 14. It corresponds in most steps to the second embodiment of the method according to the invention. However, when the first microfluidic layer 30 is covered with the cover film 50 and welded to it 63, this, in the fifth embodiment of the method according to the invention, not only closes the open area of the vacuum channel 11, but also the open area of the first chamber part 31 on this side of the first microfluidic layer 30, so that a bottom of the first chamber part 31 is formed. Otherwise, process steps 60 to 67 and 69 proceed as in the second embodiment of the method according to the invention. However, the sealing 68 of the vacuum channel 11 is omitted. Instead, it is left open and functions as a feed channel in the subsequent operation of the microfluidic device.Through this device, a liquid can be introduced into chamber 10 in such a way that it evenly fills the bottom of chamber 10 with the liquid, thus ensuring particularly effective dissolution of the reagent 20. The liquid containing the dissolved reagent 20 can then be directed through the discharge channel 13 into other chambers of the microfluidic device.
Claims
R. 416207 - 13 - Claims 1. Method for manufacturing a microfluidic device, comprising the following steps: Providing (61) a first microfluidic layer (30) comprising a first chamber part (31) into which a vacuum channel (11) opens, arranging (64) a solid reagent (20) in the first chamber part (31), Fixing (65) the reagent (20) by applying a negative pressure to the vacuum channel (11), and Arranging (67, 83) a second microfluidic layer (40) on the first microfluidic layer (30) such that the first chamber part (31) forms a chamber (10) in the microfluidic device 2. Method according to claim 1, characterized in that the second microfluidic layer (40) comprises a second chamber part (41) which together with the first chamber part (31) forms the chamber (10).
3. Method according to claim 1 or 2, characterized in that the first chamber part (31) is open on two opposite sides of the first microfluidic layer (30) and the opening facing away from the second microfluidic layer (40) is closed by means of a cover film (50), wherein the vacuum channel (11) preferably opens laterally into the first chamber part (31).
4. Method according to one of the preceding claims, characterized in that the vacuum channel (11) opens into the first chamber part (31) on the side facing away from the second microfluidic layer (40). R. 416207 - 14 - 5. Method according to one of the preceding claims, characterized in that the vacuum channel (11) opens into the first chamber part (31) through a sieve structure (33).
6. Method according to one of the preceding claims, characterized in that a feed channel (12) or a discharge channel (13) of the chamber (10) opens into the vacuum channel (11).
7. Method according to one of the preceding claims, characterized in that the vacuum channel (11) is closed (68, 83) after the arrangement (67, 82) of the second microfluidic layer (40).
8. Method according to one of the preceding claims, characterized in that the vacuum channel (11) is open to the side of the first microfluidic layer (30) facing away from the second microfluidic layer (40), its open area is covered by means of a cover film (50) (63) and the sealing (68) is carried out by melting the cover film (50) so that its melt (51) penetrates the vacuum channel.
9. Method according to one of claims 1 to 7, characterized in that the vacuum channel (11) is open to the side of the first microfluidic layer (30) facing the second microfluidic layer (40), its open area is covered (82) by means of a connecting film (70) which is arranged between the first microfluidic layer (30) and the second microfluidic layer (40) and the sealing (84) is carried out by melting the connecting film (70) so that its melt (71) penetrates the vacuum channel (11).
10. Microfluidic device comprising two interconnected microfluidic layers (30, 40) and a chamber (10), wherein a reagent (20) is arranged in the chamber (10) and a vacuum channel (11) opens into the chamber (10).
11. Microfluidic device according to claim 10, characterized in that it was manufactured by a method according to any one of claims 1 to 9. R. 416207 - 15 - 12. Method for operating a microfluidic device manufactured by a method according to any one of claims 1 to 9, characterized in that the vacuum channel (11) is used to supply a fluid into the chamber (10) or to discharge a fluid from the chamber (10).