Reagent cartridge for a microfluidic device

Abstract

The invention relates to a reagent cartridge (200) for a microfluidic device (100), comprising a plurality of reagent containers (221-223), each of which has an outlet opening that is sealed by means of a film, and each of which contains at least one reagent. A ridge (240) runs around at least portions of the outlet openings of the reagent containers (221-223). The microfluidic device (100) comprises at least one reagent cartridge (200), and the outlet openings of the reagent cartridge (200) face the microfluidic device (100).

Description

[0001] R. 417522

[0002] - 1 -

[0003] Description

[0004] title

[0005] Reagent bar for a microfluidic device

[0006] The present invention relates to a reagent bar for a microfluidic device. The present invention also relates to a microfluidic device comprising the reagent bar.

[0007] State of the art

[0008] In microfluidic devices, such as disposable microfluidic cartridges, a biological sample can be reacted with reagents for analysis. The reagents can be stored in a reagent bar, which consists of several interconnected reagent containers. A microfluidic cartridge is manufactured from structured plastic carrier plates and various interlayers. One of these carrier plates, which features microfluidic chambers and channels for transporting the biological sample and reagents, is called the fluidic carrier plate. A reagent chamber is formed within this fluidic carrier plate. One or more reagent bars are arranged in the reagent chamber before the individual components of the microfluidic cartridge are assembled and welded together.

[0009] German patent DE 102021 214481 A1 describes a microfluidic device with a reagent chamber for holding a reagent bar containing three reagent containers. The inner surfaces of the reagent chamber have projections to precisely position the reagent containers of the reagent bar within the reagent chamber. R. 417522

[0010] - 2 -

[0011] Disclosure of the invention

[0012] A reagent bar for a microfluidic device is proposed, comprising multiple reagent containers. Each reagent container has an outlet opening, which may, in particular, completely occupy one side of the container. The outlet opening is sealed with a film. Each reagent container contains at least one reagent. In particular, the reagent or reagent mixture in each reagent container differs from the reagent or reagent mixture in all other reagent containers. The reagent bar may, for example, comprise three reagent containers.

[0013] A particularly right-angled edge, preferably with a width of 0.3 mm to 1.5 mm, runs at least partially, preferably completely, around the outlet openings of the reagent containers. This edge can be used to fix the reagent bar to, in particular, one side of the microfluidic device, especially by means of a positive locking mechanism, for example, by hooking it into the microfluidic device or by snapping it into place. This eliminates the need for the microfluidic device to have a reagent chamber. The formation of a reagent chamber significantly complicates the manufacture of the microfluidic device.While, for example, disposable microfluidic cartridges can generally be manufactured from several thin plastic carrier plates, the formation of a reagent chamber requires that the fluidic carrier plate have a protruding area extending beyond the base of the plate, in which one or more reagent bars can be accommodated. This three-dimensional manufacturing process is complex and increases the material requirements for the fluidic carrier plate. Furthermore, manufacturing defects can easily occur, which are only discovered during final quality control of the microfluidic device after all reagent bars have already been placed in the reagent chamber and all components of the microfluidic device have been welded together. This leads to the loss of the entire cartridge. R. 417522.

[0014] - 3 -

[0015] When using the proposed reagent bar, the fluidic carrier plate can be manufactured planar. Only after all cartridge components have been welded together are one or more reagent bars attached. Should the final quality control reveal a defect in the cartridge, even though it is simpler to manufacture than a conventional microfluidic cartridge, the reagent bars can be removed, and only the already welded components need to be disposed of.

[0016] If the microfluidic device is a disposable cartridge for analyzing a medical sample, all its components must be biocompatible and sterile to prevent falsification of the subsequent analysis results. For this reason, all cartridge components are manufactured from special materials under cleanroom conditions and assembled in a separate cleanroom. Since a conventional reagent bar must be inserted into the reagent chamber before the carrier plates are welded, this means the reagent bar must also be installed in the cleanroom. In contrast, the proposed reagent bar can be retrofitted to a microfluidic cartridge that has already been assembled and welded in the cleanroom without any special hygiene requirements.

[0017] The reagent containers and the edge are preferably manufactured as a single piece. This allows the reagent containers and the edge to be produced together in a multi-cavity injection mold using an injection molding process.

[0018] In principle, it is possible to seal each outlet opening of a reagent container with a separate film after the reagent container has been filled with a reagent or reagent mixture. Preferably, however, a single film is provided that covers the outlet openings of all reagent containers and the edge. This makes it possible to first fill all reagent containers and then, in a single process step, to completely cover the side of the reagent bar that has the outlet openings with the film. (See film R. 417522.)

[0019] - 4 -

[0020] It can be, in particular, a plastic film and / or a metal film. The plastic used for the film is preferably a polyolefin.

[0021] In one embodiment of the reagent bar, the edge has a constant width, preferably the same width over the entire circumference of the reagent bar. In another embodiment, the edge has several recesses in which its width is reduced. In particular, it is reduced to zero. These recesses can be used to lock the reagent bars to locking elements of the microfluidic device.

[0022] A microfluidic device, comprising at least one of the proposed reagent bars, has inlet openings facing the outlet openings of the reagent bar(s). These inlet openings open into a channel system of a fluidic support plate of the microfluidic device. If the microfluidic device is a cartridge operated within a microfluidic analysis system, during its commissioning, plungers can be deflected to pierce the foil between each outlet opening of a reagent container and the corresponding inlet opening of the microfluidic device, allowing the reagents to enter the channel system of the fluidic support plate.

[0023] To fix the reagent bar to the microfluidic device, one embodiment of the microfluidic device provides for several rails, in particular two parallel rails, into which the edge of the reagent bar is inserted. These rails are preferably manufactured integrally with the fluidic support plate, so that no additional assembly effort is required during the manufacture of the microfluidic device.

[0024] Furthermore, it is preferred that the rails have a preload selected such that, when the edge of the reagent bar is inserted into the rails, the outlet openings of the reagent bar lie exactly above the inlet openings of the microfluidic device. R. 417522

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[0026] To save on plastic material, it is preferable for the rails to each have several spaced-apart sections. All sections of a rail lie on a common straight line. Each rail is thus divided into several segments. However, this is sufficient to securely fix the test tube in the rails.

[0027] In principle, it is possible to fix the test tube in a desired position solely by applying a suitably selected preload to the rails. However, to further increase the reliability of preventing the test tube from detaching from the rails during transport, it is preferable to additionally incorporate a clamping element inserted into the rails. This clamping element can exert its clamping effect through a suitably selected preload. To prevent the clamping effect from being impaired by temperature fluctuations due to differing expansion rates of the rails and the clamping element, it is preferable for the clamping element to be made of the same material as the rails.

[0028] In another embodiment of the microfluidic device, it has several locking elements, in particular locking hooks. This embodiment is designed to accommodate a reagent bar whose edge has several recesses. The locking elements each engage in one of these recesses and are thus locked to the edge of the reagent bar. In this way, the outlet openings of the reagent containers can be positioned at a precisely defined location above the inlet openings of the microfluidic device, and unintentional detachment of the reagent bar from the microfluidic device is reliably prevented.

[0029] When disposing of the microfluidic device, it is easy to disassemble it into its components and recycle it, because the reagent bar can be easily separated from the microfluidic device.

[0030] Brief description of the drawings R. 417522

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[0032] Exemplary embodiments of the invention are shown in the drawings and are explained in more detail in the following description.

[0033] Figure 1 shows an isometric representation of a microfluidic cartridge according to the prior art.

[0034] Figure 2a shows a top view of a test tube bar according to an embodiment of the invention.

[0035] Figure 2b shows a side view of the test tube according to Figure 2a.

[0036] Figure 3 shows a top view of the test tube block according to Figure 2a, the outlet openings of which have been closed by means of a foil.

[0037] Figure 4 shows a top view of a section of a microfluidic device according to an embodiment of the invention, without the test tube arranged thereon.

[0038] Figure 5a shows a top view of the microfluidic device according to Figure 4, with the reagent bar attached to it.

[0039] Figure 5b shows a side view of the microfluidic device according to Figure 5a.

[0040] Figure 6a shows a top view of a section of a microfluidic device according to an embodiment of the invention, which includes a clamping element.

[0041] Figure 6b shows a side view of the section of the microfluidic device according to Figure 6a.

[0042] Figure 7 shows a top view of a section of a microfluidic device according to another embodiment of the invention, without the test tube arranged thereon. R. 417522

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[0044] Figure 8a shows a top view of the microfluidic device according to Figure 7, with the reagent bar attached to it.

[0045] Figure 8b shows a side view of the microfluidic device according to Figure 8a.

[0046] Figure 9 shows a top view of a test tube bar according to another embodiment of the invention.

[0047] Figure 10 shows a top view of a section of a microfluidic device according to another embodiment of the invention, without the test tube arranged thereon.

[0048] Figure 11a shows a top view of the microfluidic device according to Figure 10, with the reagent bar attached to it.

[0049] Figure 11b shows a side view of the microfluidic device according to Figure 11a.

[0050] Exemplary embodiments of the invention

[0051] A prior art microfluidic device 100, designed as a disposable microfluidic cartridge, is shown in Figure 1. It has a reagent chamber 110 in which a reagent bar with three reagent containers is arranged. This device 100 was manufactured by producing a fluidic carrier plate with the reagent chamber 110, which forms the top side of the microfluidic device 100 as shown in Figure 1. The reagent bar was inserted into the reagent chamber, and the underside of the fluidic carrier plate, which has a system of microfluidic chambers and channels, was then covered with an elastomeric membrane, made, for example, of thermoplastic polyurethane. A pneumatic carrier plate, made, for example, of polycarbonate as a transparent plastic, was arranged on the opposite side of the elastomeric membrane.The fluidics carrier plate and the pneumatic carrier plate are R. 417522.

[0052] - 8 -

[0053] The transparent plastic is then welded to the elastomer membrane by means of laser irradiation. Manufacturing defects can occur in the area of ​​the reagent chamber containing the reagent bar, which therefore cannot be penetrated by the laser, or where there is a large distance between the laser source and the interface between the two carrier plates.

[0054] The microfluidic device 100 is designed to be inserted into an analytical apparatus. This apparatus has a pneumatic manifold by means of which pneumatic channels in the pneumatic carrier plate can be pressurized or depressed. This deflects the elastomer membrane into or out of chambers of the fluidic carrier plate, thereby manipulating fluid flows in the fluidic carrier plate and transporting the reagents of the reagent bar through the channel system.

[0055] A first embodiment of a reagent bar 200 according to the invention is shown in Figures 2a and 2b. This reagent bar 200 has an outlet side 210, which is designed to face inlet openings of a microfluidic device. Three reagent containers 221-223 each have an open side that functions as an outlet opening 231-233 and is located in the outlet side 210. An edge 240, which has a width b of, for example, 1.0 mm, extends around the outlet side 210 surrounding the outlet openings 231-233. The base body of the reagent bar 200, with its outlet side 210, the reagent containers 221-223, and the edge 240, was preferably manufactured in one piece from, for example, polypropylene using an injection molding process.Alternatively, the edge 240 can also only partially circumferentially around the test tube, for example on two opposite sides, for example only on the long sides of the rectangular base shape of the test tube 200.

[0056] To fill the reagent containers 221 to 223, the reagent bar 200 is positioned so that one outlet side 210 faces upwards. The reagent containers 221 to 223 are then filled through their outlet openings 231 to 233 with different reagents or reagent mixtures. R. 417522

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[0058] The outlet openings are then sealed by thermally welding the entire outlet side 210 of the reagent bar 200, including outlet openings 231 to 233 and edge 240, with a foil. The foil consists, for example, of an aluminum layer and a polypropylene layer.

[0059] A first embodiment of a microfluidic device 100 according to the invention, designed as a disposable microfluidic cartridge, is shown in Figure 4. In the area where the fluidic carrier plate of a conventional microfluidic device 100, as shown in Figure 1, would have its reagent chamber 110, inlet openings 121-123 are instead arranged on the fluidic carrier plate of this microfluidic device 100, the dimensions of which correspond to the dimensions of the outlet openings 231-233 of the reagent bar 200. The inlet openings 121 - 123 are each covered with a foil (not shown), which ensures that the microfluidic device 100 can be handled outside a cleanroom even without the attached reagent bar 200, without the risk of the microfluidic channel system of the fluidic support plate being contaminated by external influences.The three inlet openings 121-123 are arranged along a common straight line. Parallel to this straight line run two rails 131, 132, which are integrally manufactured with the fluidic carrier plate.

[0060] As shown in Figures 5a and 5b, the test tube 200, according to the first embodiment of the invention, can be inserted into the rails 131, 132 along a direction R, with the edge 240 guided in the rails 131, 132. For example, the test tube 200 has no edge on the sides transverse to the rails, i.e., on the short sides of the rectangular base of the test tube 200. The rails 131, 132 preferably have a preload selected such that the outlet openings 231-233 of the test tube 200 are positioned over the inlet openings 121 to 123 of the microfluidic device 100. When the microfluidic device 100 is inserted into an analyzer or put into operation, plungers are actuated, each passing through one of the inlet ports 121-123 and the corresponding outlet port 231-233R. 417522

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[0062] The reagents are guided through the reagent container 200, penetrating the foil that seals the respective inlet opening 121-123 and the foil 250 that seals the respective outlet opening 231-233. Since the microfluidic device 100 is inserted into the analysis device in such a way that the reagent bar 200 is positioned above the fluidic carrier plate, the reagents contained in the reagent containers 221-223 flow into the channel system of the fluidic carrier plate by gravity and can then be transported further within it.

[0063] Figures 6a and 6b show a second embodiment of the microfluidic device 100 according to the invention. This differs from the first embodiment in that a clamping piece 300 has been additionally inserted into the rails 131, 132 to secure the reagent bar 200 in the rails 131, 132. If the fluidic support plate, and thus also the rails 131, 132, are made of polycarbonate, for example, then in this embodiment the clamping piece is also made of polycarbonate.

[0064] A third embodiment of the microfluidic device 100, without the test tube holder 200 attached to it, is shown in Figure 7. This differs from the first embodiment in that the first rail 131 is divided into three sub-rails 131a-c and the second rail 132 is also divided into three sub-rails 132a-c. These sub-rails 131a-c and 132a-c are each arranged one behind the other along a straight line, which corresponds to the path of the first rail 131 and the path of the second rail 132, respectively, in the first embodiment. Figures 8a and 8b show that the test tube holder 200 can be inserted into these sub-rails 131a-c and 132a-c along a direction R and is held in them just as reliably by a suitable preload on the sub-rails 131a-c and 132a-c as in the rails 131 and 132 of the first embodiment.

[0065] Figure 9 shows a second embodiment of the test tube bar 200 according to the invention. This differs from the test tube bar 200 according to the first embodiment in that the edge 240 has four recesses 241-244. In these recesses, the width b of the edge 240 is

[0066] - 11 -

[0067] zero reduced. A first pair of recesses 241, 243 and a second pair of recesses 242, 244 are opposite each other.

[0068] A fourth embodiment of the microfluidic device according to the invention is shown in Figure 10. Omitting the reagent bar 200, it can be seen that, unlike the first embodiment of the microfluidic device 100, the first rail 131 has been replaced by two locking elements 141, 142, and the second rail 132 has been replaced by two further locking elements 143, 144. These locking elements 141-144 are designed as locking hooks. They are integrally formed with the fluidic carrier plate of the microfluidic device 100. As shown in Figures 11a and 11b, a test tube bar 200 according to the second embodiment of the invention can be inserted into the locking elements 141 - 144 along a direction R such that each of the locking elements 141 - 144 locks into one of the recesses 241 - 244 of the edge 240 of the test tube bar 200.The locking mechanism ends the insertion at a defined position, ensuring that the outlet openings 231–233 of the reagent containers 221–223 are positioned over the inlet openings 121–123 of the microfluidic device 100. Furthermore, the locking action between the reagent bar 200 and the fluidic support plate of the microfluidic device 100 prevents unintentional detachment of the reagent bar 200.

Claims

R. 417522 - 12 - Claims 1. Reagent bar (200) for a microfluidic device (100), comprising several reagent containers (221-223), each having an outlet opening (231-233) which is closed by means of a film (250), and each containing at least one reagent, characterized in that the reagent bar (200) has an edge (240) that surrounds at least the outlet openings (231-233) of the reagent containers (221-223) in sections.

2. Reagent bar (200) according to claim 1 , characterized in that the edge (240) has a width (b) in the range of 0.3 mm to 1.5 mm.

3. Reagent bar (200) according to claim 1 or 2, characterized in that the reagent containers (221-223) and the edge (240) are made in one piece.

4. Reagent bar (200) according to one of claims 1 to 3, characterized in that a film (250) covers the outlet openings (231-233) of all reagent containers (221-223) and also covers the edge (240).

5. Test tube (200) according to one of claims 1 to 4, characterized in that the edge (240) has several recesses (241-244).

6. Microfluidic device (100) comprising at least one reagent bar (200) according to any one of claims 1 to 5, wherein the outlet openings (231-233) of the reagent bar (200) face inlet openings (121-123) of the microfluidic device (100).

7. Microfluidic device (100) according to claim 6, characterized in that the microfluidic device (100) has rails (131, 132) into which the edge (240) of the test tube (200) is inserted. R. 417522 - 13 - 8. Microfluidic device (100) according to claim 7, characterized in that the rails (131 , 132) each have several spaced-apart partial rails (131a-c, 132a-c).

9. Microfluidic device (100) according to claim 7 or 8, characterized in that it further comprises a clamping piece (300) that is inserted into the rails (131, 132) and that is configured to prevent the edge (240) from being removed from the rails (131, 132).

10. Microfluidic device (100) according to claim 6, comprising at least one reagent bar (200) according to claim 5, characterized in that it has several locking elements (141-144) which are locked into the recesses (241-244) of the edge (240).

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