Microarray structure and micro-fluidic chip

Abstract

The utility model discloses a microarray structure and a micro-fluidic chip, the microarray structure does not adopt an original micropore structure, but adopts a structure in which cylinders are arranged at intervals, so that not only are nano cavities capable of positioning magnetic beads formed, but also a channel is formed between adjacent nano cavities, and the magnetic beads can be positioned through the channels. The magnetic beads falling into the micropores are prevented from being washed out of the micropore array area, and the number of the magnetic beads falling into the micropores is increased. The micro-fluidic chip adopts the micro-array structure, so that the magnetic beads falling into the micropores are prevented from being washed out of the micropore array area, the number of the magnetic beads falling into the micropores is increased, and the detection accuracy is improved.

Description

Technical Field

[0001] This utility model relates to the field of bioanalytical detection technology, and in particular to a microarray structure and a microfluidic chip. Background Technology

[0002] Single-molecule immunoassay is a disruptive new technology in the field of protein biomarker detection. It refers to the detection of single-molecule protein molecules through immunolabeling, using antibodies to capture and recognize antigens, and then labeling them with signal molecules or enzymes. This is achieved through single-molecule fluorescence signal detection or single-molecule enzymatic reactions. Typically, using nanopore technology, approximately 250,000 capture antibodies are coated onto 2.7 μm magnetic beads. During detection, biotin-labeled detection antibodies, avidin-conjugated enzymes, and substrates are added. The pretreated immunocomplex magnetic bead suspension is injected into a microfluidic chip (either after the reaction or after injection). The magnetic beads are laid flat on a plate within the microfluidic chip, and the fluorescent spots are counted using a detection device. However, during this laying process, the magnetic beads tend to stack, making it difficult to form a single layer, which affects the detection results.

[0003] To achieve the most accurate counting possible, a technology based on magnetic beads ( This technology involves carving tens of thousands of micrometer-sized micropores onto a chip, with each micropore corresponding to a magnetic bead. After pretreatment, an immune complex magnetic bead suspension flows through the micropore array structure, causing the magnetic beads to fall into the micropores and spread out. Finally, an oil phase is added to the sample well, and the device's pipette tip draws air from the chip's vent, creating negative pressure. The movement of the oil phase washes away any magnetic beads that haven't fallen into the micropore array area. The inventors discovered that existing micropore array structures use fractional-level (FL) pores, with no flow between micropores. When negative pressure is generated during air intake, magnetic beads that have already fallen into the micropores are washed out of the array area, reducing the number of magnetic beads that have fallen into the micropores. Utility Model Content

[0004] In view of this, the present invention proposes a microarray structure and a microfluidic chip, the purpose of which is to prevent the magnetic beads that have fallen into the micropores from being washed out of the micropore array area and to increase the number of magnetic beads falling into the micropores.

[0005] The solution provided by the first aspect of this utility model includes:

[0006] A microarray structure includes multiple pillars arranged at intervals on a surface, with nanocavities formed between the pillars for embedding magnetic beads, and channels provided between adjacent nanocavities; the diameter of the magnetic beads is d, the width of the nanocavities is n, where d < n < 2d; the width of the channels is k, where k < d.

[0007] As a further alternative, the cavity is surrounded by at least three pillars, with channels formed between adjacent pillars.

[0008] As a further alternative, the cavity is surrounded by at least three pillars, with channels formed between adjacent pillars.

[0009] The solution provided by the second aspect of this utility model includes:

[0010] A microfluidic chip, wherein the microfluidic chip comprises any of the above-described microarray structures.

[0011] As a further optional solution, the chip body and rubber connectors;

[0012] The chip body has a detection cavity, which is connected to an inlet channel and an outlet channel. The inlet channel is connected to an inlet port, and the outlet channel is connected to an outlet port. The microarray structure is provided on the inner bottom surface of the detection cavity.

[0013] The rubber connector is disposed at the liquid inlet and the liquid outlet, and the rubber connector is sealed to the inner wall of the liquid inlet / liquid outlet. The rubber connector is provided with a liquid passage hole that communicates with the liquid inlet / liquid outlet.

[0014] As a further optional solution, the chip body includes a base layer, an intermediate layer and a capping layer stacked in sequence;

[0015] The intermediate layer has a through-hole, and the base layer and the cover layer are respectively disposed at both ends of the through-hole so that the through-hole forms the detection cavity;

[0016] The intermediate layer has a first groove and a second groove on the side near the capping layer, or the capping layer has a second groove on the side near the intermediate layer; after the intermediate layer and the capping layer are stacked, the first groove forms the liquid inlet channel and the second groove forms the liquid outlet channel.

[0017] The cover layer is provided with the liquid inlet and the liquid outlet;

[0018] The microarray structure is disposed on the base layer.

[0019] As a further optional solution, both the inlet and the outlet are orifice-shaped;

[0020] The rubber connector is inserted into the liquid inlet / outlet, and the rubber connector and the liquid inlet / outlet are interference fit.

[0021] As a further optional solution, a first limiting step is formed in both the liquid inlet and the liquid outlet;

[0022] The rubber connector includes an integrally connected first column and second column. The width of the second column is greater than that of the first column. A second limiting step is formed between the first column and the second column. The second limiting step abuts against the first limiting step. The second column is located on the side closer to the intermediate layer.

[0023] As a further optional solution, the base layer, intermediate layer and cover layer are all transparent panels.

[0024] As a further optional solution, the base layer, intermediate layer and capping layer are bonded, thermofused or ultrasonically welded together.

[0025] Compared with the prior art, the microarray structure and microfluidic chip of this application have at least the following advantages:

[0026] This microarray structure does not use the original micropore structure, but adopts a structure with columnar spacing, which not only forms a nanocavity that can position the magnetic beads, but also forms a channel between adjacent nanocavities. When air is drawn in and negative pressure is generated and the liquid is drawn away, it prevents the magnetic beads that have fallen into the micropore from being washed out of the micropore array area, thereby increasing the number of magnetic beads that fall into the micropore.

[0027] This microfluidic chip uses this microarray structure, which can prevent magnetic beads that have fallen into the micropores from being washed out of the micropore array area, thereby increasing the number of magnetic beads falling into the micropores and improving detection accuracy. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of a microarray structure according to an embodiment of the present invention;

[0029] Figure 2 This is a schematic diagram of a microarray structure according to another embodiment of the present invention;

[0030] Figure 3 This is a schematic diagram of the structure of a microfluidic chip according to an embodiment of the present invention;

[0031] Figure 4 This is a perspective view of the structure of a microfluidic chip according to an embodiment of this utility model;

[0032] Figure 5 yes Figure 1 Cross-sectional view of AA;

[0033] Figure 6 This is one of the exploded schematic diagrams of a microfluidic chip according to an embodiment of this utility model;

[0034] Figure 7This is the second exploded view of a microfluidic chip according to an embodiment of this utility model;

[0035] Figure 8 This is a cross-sectional schematic diagram of the cover layer and the rubber connector in an embodiment of this utility model;

[0036] Figure 9 This is a schematic diagram of the structure of the rubber connector in an embodiment of this utility model;

[0037] In the diagram: 100, magnetic bead;

[0038] 1. Chip body; 1a. Base layer; 1b. Intermediate layer; 1c. Cap layer; 11. Detection cavity; 12. Liquid inlet channel; 13. Liquid outlet channel; 14. Liquid inlet; 15. Liquid outlet; 16. Perforation; 17. First groove; 18. Second groove; 19. First limiting step;

[0039] 2. Rubber connector; 21. Fluid passage hole; 22. First column; 23. Second column; 24. Second limiting step;

[0040] 3. Main body; 31. Cavity; 32. Channel. Detailed Implementation

[0041] The specific embodiments of this utility model will be described in further detail below with reference to the accompanying drawings and examples. The following examples are used to illustrate this utility model, but are not intended to limit its scope.

[0042] In the description of this utility model, it should be understood that the terms "upper", "lower", "front", "rear", "vertical", "horizontal", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model.

[0043] In this utility model, unless otherwise explicitly specified and limited, the terms "installation," "connection," "joining," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this utility model according to the specific circumstances.

[0044] In this utility model, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact through an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0045] This utility model discloses a microarray structure, including multiple pillars 3 arranged at intervals on a surface, with nanocavities 31 formed between the multiple pillars 3 for embedding magnetic beads 100, and channels 32 provided between adjacent nanocavities 31; the diameter of the magnetic beads 100 is d, the width of the nanocavities 31 is n, where d < n < 2d; the width of the channels 32 is k, where k < d.

[0046] In simple terms, the width of the nano-cavity 31 can accommodate one magnetic bead 100, but not two magnetic beads 100, ensuring a one-to-one correspondence between the nano-cavity 31 and the magnetic beads 100. The width of the channel 32 prevents the magnetic beads 100 from passing through, ensuring that the magnetic beads 100 are positioned within the nano-cavity 31. Thus, this microarray structure does not use the original micropore structure, but rather a structure with columnar spacing. This not only forms nano-cavities 31 that can position the magnetic beads 100, but also forms channels 32 between adjacent nano-cavities 31, preventing magnetic beads that have fallen into the micropores from being washed out of the micropore array area, thereby increasing the number of magnetic beads that fall into the micropores.

[0047] Specifically, the cavity 31 is formed by at least three pillars 3, and the channels 32 are formed between adjacent pillars 3 located around the cavity 31. For example:

[0048] In some embodiments, such as Figure 1 As shown, the main body 3 is a cylinder, and the cavity 31 is formed by four cylinders 3.

[0049] In some embodiments, such as Figure 2 As shown, the main body 3 is a regular prism, specifically a triangular prism; the cavity 31 is formed by six prisms 3.

[0050] This invention also discloses a microfluidic chip, which includes any of the microarray structures described above. By employing this microarray structure, the microfluidic chip can prevent magnetic beads that have fallen into the micropores from being washed out of the micropore array area, thereby increasing the number of magnetic beads falling into the micropores and improving detection accuracy.

[0051] Furthermore, leakage is prone to occur during the injection / ejection of immune complex magnetic bead suspensions using microfluidic chips; therefore, in some embodiments, such as Figure 3-5 As shown, the microfluidic chip also includes a chip body 1 and a rubber connector 2; the chip body 1 has a detection cavity 11, the detection cavity 11 is connected to an inlet channel 12 and an outlet channel 13, the inlet channel 12 is connected to an inlet port 14, and the outlet channel 13 is connected to an outlet port 15; the microarray structure is provided on the inner bottom surface of the detection cavity 11.

[0052] The rubber connector 2 is disposed at the liquid inlet 14 and the liquid outlet 15. The rubber connector 2 is sealed to the inner wall of the liquid inlet 14 / liquid outlet 15. The rubber connector 2 is provided with a liquid passage hole 21 that connects the liquid inlet channel 12 / liquid outlet channel 13.

[0053] Specifically, the injection device / drainage device (external device not shown) is connected to the rubber connector 2. The rubber connector 2 can be sealed and connected to the injection device / drainage device. The injection device can inject the immune complex magnetic bead suspension into the liquid passage 21 of the rubber connector 2, and the immune complex magnetic bead suspension flows into the detection chamber 11 through the liquid inlet channel 12. Subsequently, the detection device can be used to count the fluorescent spots of the immune complex magnetic beads in the detection chamber 11. When it is necessary to drain the detected liquid in the detection chamber 11, the detected liquid is discharged to the drainage device along the liquid outlet channel 13.

[0054] The microfluidic chip has rubber connectors 2 on the inlet 14 and outlet 15. The rubber connectors 2 can be used to seal with the injection / drainage device, improving the sealing performance when the microfluidic chip is connected to the injection / drainage device and avoiding leakage.

[0055] In some embodiments, to facilitate the formation of structures such as a detection cavity 11, a liquid inlet channel 12, a liquid outlet channel 13, a liquid inlet 14, and a liquid outlet 15 on the chip body 1, such as... Figure 6 and Figure 7 As shown, the chip body 1 includes a base layer 1a, an intermediate layer 1b, and a cover layer 1c stacked sequentially; a through hole 16 is provided on the intermediate layer 1b, and the base layer 1a and the cover layer 1c are respectively disposed at both ends of the through hole 16 so that the through hole 16 forms the detection cavity 11.

[0056] The aforementioned three-layer structure allows for easy engraving of the microarray structure on the base layer.

[0057] Furthermore, to facilitate the formation of the inlet channel 12 and the outlet channel 13, in this embodiment, as follows: Figure 6 and Figure 7As shown, the cover layer 1c has a first groove 17 and a second groove 18 on the side near the intermediate layer 1b. After the intermediate layer 1b and the cover layer 1c are stacked, the first groove 17 forms the liquid inlet channel 12, and the second groove 18 forms the liquid outlet channel 13. In addition, the cover layer 1c has a liquid inlet 14 and a liquid outlet 15.

[0058] In some embodiments, to facilitate a sealed connection between the rubber connector 2 and the inner wall of the inlet 14 / outlet 15, such as... Figure 5 and Figure 8 As shown, both the inlet 14 and the outlet 15 are perforated; the rubber connector 2 passes through the inlet 14 / outlet 15, and the rubber connector 2 and the inlet 14 / outlet 15 are interference-fitted. This ensures that there are no gaps between the rubber connector 2 and the inner wall of the inlet 14 / outlet 15, preventing leakage.

[0059] Specifically, to ensure the stable installation of rubber connector 2, the above solution includes, for example... Figure 8 and Figure 9 As shown, both the inlet 14 and the outlet 15 have a first limiting step 19. The rubber connector 2 includes a first column portion 22 and a second column portion 23 integrally connected. The width of the second column portion 23 is greater than that of the first column portion 22. A second limiting step 24 is formed between the first column portion 22 and the second column portion 23. The second limiting step 24 abuts against the first limiting step 19. The second column portion 23 is located on the side closer to the intermediate layer 1b. By setting the first limiting step 19 and the second limiting step 24, when the intermediate layer 1b and the cover layer 1c are stacked and fixed, it can be ensured that the rubber connector 2 will not detach from the cover layer 1c.

[0060] like Figure 9 As shown, the outer periphery of the first column portion 22 and / or the second column portion 23 is non-circular, so that the rubber connector 2 cannot rotate within the liquid inlet 14 / liquid outlet 15, further ensuring the installation stability of the rubber connector 2.

[0061] In the above scheme, the base layer 1a, the intermediate layer 1b, and the cover layer 1c are bonded, thermofused, or ultrasonically welded together. Furthermore, as... Figure 4 As shown, the chip body 1 has multiple detection cavities 11, liquid inlet channels 12, liquid outlet channels 13, liquid inlets 14 and liquid outlets 15.

[0062] In the above embodiments, the descriptions of each embodiment have different focuses. For parts not described in detail in a certain embodiment, please refer to the relevant descriptions in other embodiments.

[0063] The above description is only a preferred embodiment of the present utility model. It should be noted that for those skilled in the art, several improvements and substitutions can be made without departing from the technical principles of the present utility model, and these improvements and substitutions should also be considered within the protection scope of the present utility model.

Claims

1. A microarray structure, characterized by, The microarray structure comprises a plurality of columns arranged in an array on a surface, a plurality of nanocavities formed between the columns for embedding magnetic beads, and channels formed between adjacent nanocavities; the magnetic beads have a diameter d, the nanocavities have a width n, and d < n < 2d; and the channels have a width k, and k < d.

2. The microarray structure according to claim 1, wherein The nanocavities are surrounded by at least three columns, and the channels are formed between adjacent columns.

3. The microarray structure according to claim 2, wherein The columns are cylindrical or prismatic.

4. A microfluidic chip, characterized by, The microfluidic chip comprises the microarray structure of any one of claims 1-3.

5. The microfluidic chip of claim 4, wherein, Further comprising: a chip body and a rubber connecting piece; a detection cavity is arranged in the chip body, and a liquid inlet channel and a liquid outlet channel are connected to the detection cavity, the liquid inlet channel is communicated with a liquid inlet, and the liquid outlet channel is communicated with a liquid outlet; and a microarray structure is arranged on the inner bottom surface of the detection cavity; the rubber connecting piece is arranged at the liquid inlet and the liquid outlet, and is sealingly connected to the inner wall of the liquid inlet / liquid outlet; and a liquid passage hole is arranged on the rubber connecting piece and communicated with the liquid inlet channel / liquid outlet channel.

6. The microfluidic chip of claim 5, wherein, Further comprising: the chip body comprises a base layer, an intermediate layer, and a cover layer arranged in sequence; a through hole is formed in the intermediate layer, and the base layer and the cover layer are arranged at two ends of the through hole, so that the through hole forms the detection cavity; a first groove and a second groove are formed in the side of the cover layer close to the intermediate layer; and after the intermediate layer and the cover layer are stacked, the first groove forms the liquid inlet channel, and the second groove forms the liquid outlet channel; the cover layer is provided with the liquid inlet and the liquid outlet; the base layer is provided with the microarray structure.

7. The microfluidic chip of claim 6, wherein, Further comprising: the liquid inlet and the liquid outlet are both holes; the rubber connecting piece is arranged in the liquid inlet / liquid outlet, and is in interference fit with the liquid inlet / liquid outlet.

8. The microfluidic chip of claim 7, wherein, Further comprising: first limiting steps are formed in the liquid inlet and the liquid outlet; the rubber connecting piece comprises a first column portion and a second column portion connected integrally, the width of the second column portion is greater than that of the first column portion, a second limiting step is formed between the first column portion and the second column portion, the second limiting step abuts against the first limiting step, and the second column portion is located on the side close to the intermediate layer.

9. The microfluidic chip of claim 6, wherein, Further comprising: the base layer, the intermediate layer, and the cover layer are all transparent plate members.

10. The microfluidic chip of claim 6, wherein, Further comprising: the base layer, the intermediate layer, and the cover layer are connected by adhesion, hot melting, or ultrasonic welding.

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