High-throughput detection chip

Abstract

The present application relates to the biomedical field, disclose a kind of high-throughput detection chip, comprising: backplate, cover plate and connector;Wherein: backplate and cover plate are oppositely arranged, and backplate and cover plate are connected to form multiple accommodating cavities in box;Backplate is provided with detection chip unit unit corresponding to accommodating cavity on the side towards cover plate, and each detection chip unit is located in corresponding accommodating cavity;Each accommodating cavity is provided with liquid inlet and liquid outlet;Connector includes pipeline corresponding to accommodating cavity, each pipeline is provided with valve structure for controlling pipeline on-off, and in each pair of corresponding pipeline and accommodating cavity, the inlet of pipeline is communicated with the liquid outlet of accommodating cavity;Wherein, multiple pipelines form at least one pipeline group, each pipeline group includes at least two pipelines, and the pipeline in each pipeline group shares a sample liquid outlet.The detection flexibility and accuracy of detection chip unit are improved, and then the detection efficiency is improved.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a high-throughput detection chip. Background Technology

[0002] Polymerase chain reaction (PCR) is a molecular biology technique used to amplify specific DNA fragments, significantly increasing trace amounts of deoxyribonucleic acid (DNA). Unlike traditional PCR, digital polymerase chain reaction (dPCR) is a quantitative analysis method that provides digital DNA information, demonstrating significant advantages in multiple fields since its inception. Due to its high sensitivity, specificity, high throughput, and accurate quantification, dPCR is widely used in clinical diagnostics, gene instability analysis, single-cell gene expression, environmental microbial detection, and prenatal diagnosis. Summary of the Invention

[0003] This invention discloses a high-throughput detection chip, which improves the detection flexibility and accuracy of the detection chip unit, thereby improving detection efficiency.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] A high-throughput detection chip includes: a backplane, a cover plate, and a connector; wherein:

[0006] The back plate and the cover plate are disposed opposite to each other, and the back plate and the cover plate form a plurality of receiving cavities; the back plate is provided with a detection chip unit corresponding to each receiving cavity on the side facing the cover plate, and each detection chip unit is located in the corresponding receiving cavity; each receiving cavity is provided with a liquid inlet and a liquid outlet;

[0007] The connector includes pipes that correspond one-to-one with the receiving cavities. Each pipe is provided with a valve structure for controlling the opening and closing of the pipe. In each pair of corresponding pipes and receiving cavities, the inlet of the pipe is connected to the outlet of the receiving cavity. Multiple pipes form at least one pipe group. Each pipe group includes at least two pipes. The pipes in each pipe group share a sample liquid outlet.

[0008] In the high-throughput detection chip provided by the above technical solution, a backplate and a cover plate arranged opposite each other form multiple receiving cavities. Each receiving cavity contains a detection chip unit. During specific detection, according to actual needs, the valve structure on the pipeline corresponding to the receiving cavity to be used is opened. At this time, if the receiving cavities corresponding to other pipelines in the same pipeline group are not used, the valve structure on the pipeline corresponding to the unused receiving cavity can be closed. If all receiving cavities corresponding to the same pipeline group are to be used, the valve structure on all pipelines in the pipeline group is opened. Then, sample liquid is injected into the receiving cavity through the liquid inlet of the corresponding receiving cavity, so that the sample liquid can enter the reaction chambers of the detection chip unit in the receiving cavity for subsequent detection. In addition, when it is necessary to encapsulate and divide the reaction chambers of the detection chip unit in the receiving cavity after the sample liquid is filled, the excess sample liquid will be discharged from the sample liquid outlet of the pipeline group to which the corresponding pipeline belongs.

[0009] As can be seen from the above analysis, the high-throughput detection chip provided by the above solution allows for flexible selection of the required receiving chamber through the adjustment of the valve structure. Furthermore, it can prevent sample liquid from entering the empty receiving chamber and causing contamination. During subsequent use, the possibility of contamination of each receiving chamber is very small, which can improve the detection accuracy when the corresponding receiving chamber is used.

[0010] Preferably, the back plate and the cover plate are connected by a sealing adhesive layer, and the receiving cavity is formed by the sealing adhesive layer.

[0011] Preferably, the liquid outlet of the receiving cavity is formed in the cover plate, the pipes in the connector are connecting pipes, and each of the connecting pipes is located on the side of the cover plate away from the back plate.

[0012] Preferably, the sealing adhesive layer has a first groove formed on the surface away from the back plate. The first groove has a bottom and two opposite sidewalls and an opening on one side facing the cover plate. The cover plate covers the first groove, and the surface of the cover plate facing the back plate cooperates with the first groove to form the conduit of the connector. One end of the conduit communicates with the receiving cavity to form the liquid outlet of the receiving cavity, and the cover plate is provided with sample liquid outlets corresponding one-to-one with the conduit group.

[0013] Preferably, the valve structure includes a pneumatic valve.

[0014] Preferably, in each pair of corresponding air valves and pipelines:

[0015] The air valve includes an elastic valve plate, the edge of which is sealed to the cover plate to form an air-controlled chamber. The elastic valve plate covers the first groove along the arrangement direction of the two side walls, with its orthogonal projection on the sealing frame adhesive layer. The cover plate has a through hole that communicates with the air-controlled chamber and is configured as an air-controlled inlet. When a set pressure gas is introduced into the air-controlled chamber from the air-controlled inlet, the elastic valve plate deforms and extends into the first groove, fitting against the bottom of the first groove and the two side walls.

[0016] Preferably, in each pair of corresponding air valves and pipelines, the air control inlet does not overlap between the orthographic projection of the back plate and the orthographic projection of the first groove on the back plate.

[0017] Preferably, the back plate has a slot formed on the surface facing the cover plate for at least one of the back plates, and the detection chip unit is installed in the slot.

[0018] Preferably, the detection chip unit is formed on the surface of the backplate facing the cover plate.

[0019] Preferably, the cover plate has a flexible elastic film on the side facing the back plate that corresponds to each of the receiving cavities. The flexible elastic film is located inside the receiving cavity, and the edge of the flexible elastic film is sealed to the surface of the cover plate facing the back plate, so that an air passage space is formed between the flexible elastic film and the cover plate. In each pair of corresponding flexible elastic films and receiving cavities, the orthographic projection of the flexible elastic film on the back plate covers the detection chip unit inside the receiving cavity, and there is no overlap between the orthographic projection of the liquid inlet and liquid outlet of the receiving cavity on the back plate and the orthographic projection of the air passage space on the back plate.

[0020] The cover plate is provided with an air inlet and an air outlet in the area forming the gas passage space, both extending along its own thickness direction. The air inlet and the air outlet are only connected to the gas passage space, so that when gas is filled from the air inlet, the flexible elastic film deforms and covers each reaction chamber of the detection chip unit.

[0021] Preferably, in each of the receiving cavities, the air inlet and air outlet provided on the cover plate do not overlap with the orthographic projection of the detection chip unit on the back plate.

[0022] Preferably, the edge of the flexible elastic film is bonded to the surface of the cover plate facing the back plate.

[0023] Preferably, the thickness of the flexible elastic film is 5μm-90μm.

[0024] Preferably, the portion of the cover plate used to form the air passage space forms an inflation groove on the surface facing the back plate, the flexible elastic film covers the opening of the inflation groove, and the orthographic projections of the air inlet and the air outlet on the back plate are located within the orthographic projection of the inflation groove on the back plate.

[0025] Preferably, in each of the receiving cavities, the projection of the inflation groove on the back plate covers each reaction chamber of the detection chip unit within the receiving cavity.

[0026] Preferably, the depth of the air-filled groove is 20μm-1000μm along the direction perpendicular to the cover plate.

[0027] Preferably, the plurality of card slots are arranged in an array.

[0028] Preferably, the plurality of slots are arranged in a ring around the sample liquid outlet of the connector.

[0029] Preferably, the detection chip unit further includes a temperature control layer; the temperature control layer is disposed on the back plate and is used to heat the plurality of reaction chambers.

[0030] Preferably, the detection chip unit further includes a voltage control unit, which is electrically connected to the temperature control layer. Attached Figure Description

[0031] Figure 1 This is a top view of a high-throughput detection chip provided in an embodiment of the present invention;

[0032] Figure 2 for Figure 1 The diagram shows the structure of the backplane in the high-throughput detection chip.

[0033] Figure 3 The diagram shows the structure of the cover plate in the high-throughput detection chip shown in Figure 1.

[0034] Figure 4 This is a top view schematic diagram of a high-throughput detection chip provided in an embodiment of the present invention;

[0035] Figure 5 for Figure 1 The diagram shows a structural schematic of a connector in a high-throughput detection chip.

[0036] Figure 6 for Figure 5 A schematic diagram showing one possible on / off selection for each conduit in the connector shown;

[0037] Figure 7 for Figure 5 A schematic diagram showing another on / off option for each conduit in the connector shown;

[0038] Figure 8 This is a schematic diagram of a specific arrangement structure of the connector in the high-throughput detection chip provided in an embodiment of the present invention;

[0039] Figure 9 This is a schematic diagram of another specific arrangement structure of the connector in the high-throughput detection chip provided in an embodiment of the present invention;

[0040] Figure 10 This is a schematic diagram of another specific arrangement structure of the connector in the high-throughput detection chip provided in an embodiment of the present invention;

[0041] Figure 11 This is a schematic diagram of another specific arrangement structure of the connector in the high-throughput detection chip provided in an embodiment of the present invention;

[0042] Figure 12 This is a schematic diagram of the specific structure of a connector in a high-throughput detection chip provided in an embodiment of the present invention;

[0043] Figure 13 for Figure 10 A schematic diagram of a valve structure in the connector shown;

[0044] Figure 14 This is a schematic diagram of a specific structure of the detection chip unit in the high-throughput detection chip provided in an embodiment of the present invention;

[0045] Figures 15-18 This is a structural diagram illustrating the fabrication process of the detection chip unit in the high-throughput detection chip provided in an embodiment of the present invention.

[0046] Figure 19 This is a schematic diagram of a specific structure of a cavity in a high-throughput detection chip provided in an embodiment of the present invention;

[0047] Figure 20 This is a schematic diagram of another specific structure of a receiving cavity in a high-throughput detection chip provided in an embodiment of the present invention;

[0048] Figure 21 This is a schematic diagram of the structure of a high-throughput detection chip in use according to an embodiment of the present invention;

[0049] Figure 22 This is a structural schematic diagram of another usage state of a backplate provided in an embodiment of the present invention.

[0050] In the diagram: 1-Backplate; 11-Receiving cavity; 12-Detection chip unit; 120-Reaction chamber; 121-Control circuit; 1211-Voltage control unit; 122-First passivation layer; 1221-Via; 123-Temperature control layer; 124-Second passivation layer; 125-Black matrix; 126-Confinement layer; 127-Hydrophilic layer; 128-First substrate; 2-Cover plate; 21-Liquid inlet; 22-Liquid outlet; 23-Air inlet; 24-Air outlet; 25-Flexible elastic film; 26-Gas path space; 261-Third passivation layer; 27-Second substrate; 3-Connector; 31-Pipeline; 311-Valve structure; 3111-Pneumatic control chamber; 3112-Pneumatic control air inlet; 3113-Elastic valve plate; 32-Inlet; 33-Sample liquid outlet; 5-Sealing adhesive layer. Detailed Implementation

[0051] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0052] Digital PCR utilizes microfluidic technology to disperse the test liquid and PCR reagent mixture into individual miniature reaction chambers within the detection chip unit, allowing for independent PCR amplification of the target molecules in each reaction chamber.

[0053] like Figure 1 As shown, and refer to Figure 2 and Figure 3 The present invention provides a high-throughput detection chip, comprising: a backplate 1, a cover plate 2, and a connector 3;

[0054] The back plate 1 and the cover plate 2 are arranged opposite to each other, and the back plate 1 and the cover plate 2 are connected to form a plurality of receiving cavities 11. The back plate 1 facing the cover plate 2 is provided with a detection chip unit 12 corresponding to each receiving cavity 11. Each detection chip unit 12 is located in the corresponding receiving cavity 11. Each receiving cavity 11 has a liquid inlet 21 and a liquid outlet 22.

[0055] The connector 3 includes a pipe 31 corresponding to the receiving cavity 11. Each pipe 31 is provided with a valve structure 311 for controlling the opening and closing of the pipe. In each pair of corresponding pipes 31 and receiving cavities 11, the inlet 32 ​​of the pipe 31 is connected to the outlet 22 of the receiving cavity 11. Multiple pipes 31 form at least one pipe group. Each pipe group includes at least two pipes 31. The pipes 31 in each pipe group share a sample liquid outlet 33.

[0056] In the high-throughput detection chip provided by the above technical solution, the backplate 1 and cover plate 2, which are arranged opposite to each other, cooperate to form multiple receiving cavities 11. Each receiving cavity 11 contains a detection chip unit 12. During specific detection, according to actual needs, the valve structure 311 on the pipe 31 corresponding to the receiving cavity 11 to be used is opened. At this time, if the receiving cavities 11 corresponding to other pipes in the same pipe group as the receiving cavity 31 are not used, the valve structure 311 on the pipe 31 corresponding to the receiving cavity 11 that is not used can be closed. If the receiving cavities 11 corresponding to other pipes in the same pipe group are not used, the valve structure 311 on the pipe 31 corresponding to the receiving cavity 11 that is not used can be closed. If all the receiving cavities 11 need to be used, the valve structures 311 on all the pipelines 31 in the pipeline group are opened; then, sample liquid is injected into the receiving cavity 31 through the liquid inlet 21 of the corresponding receiving cavity 11, so that the sample liquid can enter the reaction chambers of the detection chip unit 12 provided in the receiving cavity 11 for subsequent detection; in addition, when it is necessary to encapsulate and divide the reaction chambers of the detection chip unit in the receiving cavity 11 after it has been filled with sample liquid, the excess sample liquid will be discharged from the sample liquid outlet 33 of the pipeline group to which the corresponding pipeline 31 belongs.

[0057] The selection of conduit in connector 3 can be based on Figure 1 The following description uses connector 3 of the high-throughput detection chip as an example. Please refer to [reference needed]. Figure 5 , Figure 6 and Figure 7 One end of the tube 31 in connector 3 forms an inlet 32, and the other end of tube 31 is connected to the sample liquid outlet 33; specifically, connector 3 includes six tubes, namely tube a, tube b, tube c, tube d, tube e, and tube f. Under one operating condition, such as... Figure 6 As shown, the valves on pipes a and d are closed, while the valves on pipes b, c, e, and f are open; under another operating condition, as... Figure 7 As shown, the valve structures on pipelines a, d, and e are closed, while the valve structures on pipelines b, c, and f are open.

[0058] As can be seen from the above analysis, in the high-throughput detection chip provided by the above solution, the required receiving cavity 11 can be flexibly selected through the adjustment of the valve structure 311. Furthermore, it can prevent sample liquid from entering the empty receiving cavity and causing contamination. In subsequent use, the possibility of each receiving cavity being contaminated is very small, which can improve the detection accuracy when the corresponding receiving cavity is used.

[0059] Figure 1 and Figure 4 In the high-throughput detection chip provided, the connector 3 has multiple conduits 31 forming a conduit group, that is... Figure 1 and Figure 4Each connector has six tubing channels 31, and all six channels 31 share a single sample outlet 33. Specifically, the multiple tubing channels 31 of the connector 3 can form two or more tubing groups. Taking a connector with six tubing channels as an example:

[0060] The six pipes 31 can form two pipe groups, one of which includes two pipes and the other includes four pipes; or, both pipe groups may each include three pipes.

[0061] The six pipes 31 can form three pipe groups, each of which includes two pipes.

[0062] Of course, connector 3 includes multiple pipes that can be allocated according to actual needs.

[0063] The multiple pipes 31 in connector 3 can be combined and allocated according to actual needs, which can further improve the flexibility of the high-throughput detection chip.

[0064] In the high-throughput detection chip provided in the above embodiments, the receiving cavity 11 formed by the backplate 1 and the cover plate 2 can have various distribution patterns, such as:

[0065] Method 1: The receiving cavity 11 can be Figure 1 In the distribution shown, the orthographic projection of the sample liquid outlet 33 onto the surface of the cover plate 2 away from the back plate 1 is located at the center of the cover plate 2. The multiple receiving cavities 11 are evenly distributed around the center of the cover plate 2 in a circumferential direction, with their orthographic projections onto the surface of the cover plate 2 away from the back plate 1. At this time, the orthographic projection of the connector 3 onto the cover plate 2 is a radial shape centered on the center of the cover plate 2. Figure 1 As shown in the image.

[0066] Method two, the receiving cavity 11 can also be Figure 4 The distribution shown is an array of two rows and three columns. In this case, the specific structure of connector 3 is also modified. For example, pipe 31 is located between the two rows of receiving cavities 11 and is connected to the sample liquid outlet 33 via a main pipe. Figure 4 The structure shown.

[0067] Based on the high-throughput detection chip provided in the above embodiments, the plurality of accommodating cavities can be formed in the following manner, please refer to... Figure 1 and Figure 2 refer to Figure 8 and Figure 9In this embodiment, the backplate 1 and the cover plate 2 are connected by a sealing adhesive layer 5, and the receiving cavity 11 is formed by the sealing adhesive layer 5. In the high-throughput detection chip provided in this embodiment, the multiple receiving cavities 11 mentioned above are formed by the sealing adhesive layer 5 separating the backplate 1 and the cover plate 2. It is not necessary to process special structures on the backplate 1 or the cover plate 2 to form the receiving cavities 11, which is convenient for manufacturing and can simplify the overall structure of the high-throughput detection chip.

[0068] Specifically, based on the high-throughput detection chips provided in the above embodiments, the arrangement structure of the receiving cavity 11 and the connector 3 in the high-throughput detection chip can also be varied, such as:

[0069] In the first alternative implementation, such as Figure 8 As shown, Figure 8 This is a schematic diagram of a specific structure of the receiving cavity and connector in the high-throughput detection chip provided in an embodiment of the present invention. In this detection system, the liquid outlet 22 of the receiving cavity 11 is formed on the cover plate 2 and penetrates the cover plate 2 along the arrangement direction of the cover plate 2 and the back plate 1, that is, the liquid outlet 22 penetrates the thickness direction of the cover plate 2. The pipe 31 in the connector 3 is a connecting pipe, and each connecting pipe is located on the side of the cover plate 2 away from the back plate 1. The side of the cover plate 2 away from the back plate is provided with a sample liquid outlet 33.

[0070] Preferably, the pipes 31 in the connector 3 are detachably connected to the cover plate 2. This allows the composition of each pipe group in the connector 3 to be changed at any time according to the working conditions, and the correspondence between each pipe group and the receiving cavity 11 to be adjusted, further improving the flexibility of the high-throughput detection chip.

[0071] Furthermore, in the connector structure described above, the valve structure 311 provided in each pipeline 31 can be a solenoid valve, a switching valve, or the like, which is convenient to install and easy to maintain.

[0072] In the second alternative implementation, such as Figure 9 As shown, Figure 9 This is a schematic diagram of another specific structure of the receiving cavity and connector in the high-throughput detection chip provided in the embodiment of the present invention. When the back plate 1 and the cover plate 2 of the high-throughput detection chip are connected by the sealing frame adhesive layer 5, the surface of the sealing frame adhesive layer 5 away from the back plate 1 forms a first groove. The first groove has a bottom and two opposite sidewalls and an opening on the side facing the cover plate 2. The cover plate 2 covers the first groove, and the surface of the cover plate 2 facing the back plate 1 cooperates with the first groove to form the pipe 31 of the connector 3. The end of the pipe 31 that communicates with the receiving cavity 11 forms the liquid outlet 22 of the receiving cavity 11, and the cover plate 2 is provided with a sample liquid outlet 33 corresponding to the pipe group.

[0073] The connector 3 assembly is formed between the cover plate 2 and the back plate 1, which can reduce the size of the high-throughput detection chip in the thickness direction and simplify the structure of the surface of the high-throughput detection chip, making it easier to clean and maintain.

[0074] In a third alternative implementation, such as Figure 10 As shown, Figure 10 This is a schematic diagram of another specific structure of the receiving cavity and connector in the high-throughput detection chip provided in the embodiment of the present invention. When the back plate 1 and the cover plate 2 of the high-throughput detection chip are connected by the sealing frame adhesive layer 5, the surface of the sealing frame adhesive layer 5 facing the back plate 1 forms a first groove. The first groove has a bottom and two opposite sidewalls and an opening on one side facing the back plate 1. The back plate 1 covers the first groove, and the surface of the back plate 1 facing the cover plate 2 cooperates with the first groove to form the pipe 31 of the connector 3. One end of the pipe 31 that communicates with the receiving cavity 11 forms the liquid outlet 22 of the receiving cavity 11, and the cover plate 2 is provided with a sample liquid outlet 33 corresponding to the pipe group.

[0075] In the fourth optional implementation, such as Figure 11 As shown, Figure 11 This is a schematic diagram of another specific structure of the receiving cavity and connector in the high-throughput detection chip provided in the embodiment of the present invention. When the back plate 1 and the cover plate 2 of the high-throughput detection chip are connected by the sealing frame adhesive layer 5, the sealing frame adhesive layer 5 is provided with a first groove penetrating its thickness direction. The first groove has two opposing sidewalls. The back plate 1 covers the opening of the first groove facing the back plate 1, and the cover plate 2 covers the opening of the first groove facing the cover plate 2. The surface of the back plate 1 facing the cover plate 2 and the surface of the cover plate 2 facing the back plate 1 cooperate with the first groove to form the pipe 31 of the connector 3. One end of the pipe 31 that communicates with the receiving cavity 11 forms the liquid outlet 22 of the receiving cavity 11, and the cover plate 2 is provided with a sample liquid outlet 33 corresponding to the pipe group.

[0076] Furthermore, when the high-throughput detection chip in the second, third, and fourth optional implementations above uses the above-mentioned connector, the valve structure 311 provided on the pipeline 31 in the connector 3 can be an air valve. The air valve has a fast response speed and will not cause pollution to the internal space of the pipeline 31.

[0077] Specifically, with Figure 1 Taking the arrangement of connector 3 in the high-throughput detection chip shown in the diagram as an example, the way air valves are installed on each pipe 31 in connector 3 is as follows: Figure 12 As shown.

[0078] In one optional embodiment, the air valve has the following structure: Figure 13 As shown, in each pair of corresponding air valves and pipes 31:

[0079] The air valve includes a resilient valve plate 3113. The edge of the resilient valve plate 3113 is sealed to the cover plate 2 so that the resilient valve plate 3113 and the cover plate 2 form an air-controlled chamber 3111. The resilient valve plate 3113, in the orthographic projection of the sealing frame adhesive layer 5, covers the first groove along the arrangement direction of the two sidewalls of the first groove. The cover plate 2 has a through hole that communicates with the air-controlled chamber 3111 and is configured as an air-controlled inlet 3112. When gas at a set pressure is injected into the air-controlled chamber 3111 from the air-controlled inlet 3112, the resilient valve plate 3113 deforms and extends into the first groove, fitting against the bottom and two sidewalls of the first groove to block the pipeline 31 formed by the first groove and the cover plate 2. The deformation process of the resilient valve plate 3113 is as follows: Figure 13 The shape of the solid line portion changes to the shape shown by the dashed line.

[0080] The elastic valve plate 3113 can be an elastic deformation membrane. Specifically, the material of the elastic deformation membrane can be polydimethylsiloxane.

[0081] Preferably, please combine Figure 12 refer to Figure 13 In each pair of corresponding air valves and pipes 31, the air control inlet 3112 does not overlap with the orthographic projection of the first groove on the back plate 1.

[0082] Based on the detection systems provided in the above embodiments, in one embodiment, such as Figure 14 As shown, the specific structure of the detection chip unit 12 may include: multiple reaction chambers 120 arranged in an array, a temperature control layer 123 for regulating the temperature of the reaction chambers 120, and a voltage control unit 1211 for controlling the voltage of the temperature control layer. The temperature of the temperature control layer 123 is controlled by the voltage control unit 1211, thereby regulating the temperature of the reaction chambers 120.

[0083] In the above detection system, there are several ways to arrange the detection chip unit 12 and the backplane 1:

[0084] Method 1: The detection chip unit 12 is detachably connected to the backplate 1. This method allows the detection chip unit 12 to be replaced according to actual needs. For example, if the detection chip unit 12 is contaminated, it can be replaced with the same type of detection chip. Alternatively, different types of detection chip units 12 can be replaced.

[0085] In one specific implementation, the surface of the back plate 1 facing the cover plate 2 has slots (not shown in the figure) that correspond one-to-one with the detection chip unit 12. In each pair of corresponding slots and detection chips, the detection chip is installed in the slot.

[0086] Method 2: The detection chip unit 12 is directly formed on the surface of the back plate 1 facing the cover plate 2, that is, the back plate 1 is directly used as a substrate, and the detection chip is directly formed on the back plate 1 through the fabrication process.

[0087] For details regarding the preparation process and flow of Method 2 above, please refer to [link / reference]. Figures 15-18 The materials and preparation process of the above-mentioned membrane will be described in detail later:

[0088] refer to Figure 15 The first substrate 128 is used to clean the surface facing the cover plate 2, and a metal layer is deposited on the first substrate 128. A control circuit 121 for controlling the temperature of the temperature control layer 123 is formed by a patterning process. The control circuit 121 includes the voltage control unit 1211 mentioned in the above embodiment. The metal layer can be made of materials such as Mo (molybdenum) and Al (aluminum), for example, Mo-Al-Mo stacked, and the thickness of each layer can be selected according to actual needs.

[0089] refer to Figure 16 A first passivation layer 122 is formed on the control circuit 121, and a via 1221 is etched into the first passivation layer 122 to expose the control circuit 121.

[0090] refer to Figure 17 A temperature control layer 123 is sputtered onto the first passivation layer 122. For example, the temperature control layer 123 can be prepared using ITO (indium tin oxide). By controlling the different thicknesses of ITO and patterning the resistance of the temperature control layer, the heating power can be changed, thereby improving the temperature uniformity.

[0091] refer to Figure 18 A second passivation layer 124 is prepared on the temperature control layer 123. The second passivation layer 124 is used to protect the temperature control layer 123 and prevent the liquid to be tested from corroding the temperature control layer 123. In addition, the second passivation layer 124 can also play a planarization role. Then, a black matrix 125 and a limiting layer 126 are formed sequentially. For example, the material of the limiting layer 126 can be photoresist. The photoresist is patterned once to obtain the limiting layer 126. The photoresist is exposed and developed using a mask to form multiple reaction chambers 120 in the photoresist. A hydrophilic layer 127 is formed on the reaction chambers 120. For example, the material of the hydrophilic layer 127 is silicon dioxide (SiO2) or silicon nitride (SiN). x ), etc. Both silicon dioxide and silicon nitride are hydrophilic. The hydrophilic layer 127 can also be prepared using other suitable materials, as long as the side of the hydrophilic layer 127 away from the limiting layer 126 is hydrophilic.

[0092] At this point, the detection chip fabrication is complete.

[0093] Of course, after the detection chip unit 12 is prepared, the cover plate 2 and the back plate 1 need to be connected to the box. For details, please refer to [reference needed]. Figure 19 A sealing layer 5 is formed on the black matrix 125. The material of the sealing layer 5 can be a suitable material such as UV adhesive. After the back plate 1 and the second substrate 27 are cured and encapsulated by the sealing layer 5, the sealing layer 5 can be used to support the gap between the back plate 1 and the cover plate 2. A third passivation layer 261 is formed on the surface of the second substrate 27 facing the back plate 1.

[0094] The first passivation layer 122, the second passivation layer 124, and the third passivation layer 261 can all be made of the same insulating material, such as silicon dioxide or silicon nitride.

[0095] The detection systems provided in the above embodiments require sealing of each reaction chamber 120 of the detection chip unit 12 during use. A common practice is to seal the chamber 11 with mineral oil or similar substances via secondary injection. However, this oil-phase liquid sealing method is complex, cumbersome, and yields inconsistent results. Therefore, designing a flexibly adjustable gas valve for reaction chamber segmentation will improve the accuracy of the detection results and facilitate operation.

[0096] The following section provides a detailed explanation of the specific structure within the detection chip:

[0097] Please refer to Figure 20 , Figure 21 and Figure 22 In the detection system provided in this embodiment of the invention, a flexible elastic film 25 corresponding to the receiving cavity 11 is provided on the side of the cover plate 2 facing the back plate 1. The flexible elastic film 25 is located in the receiving cavity 11, and the edge of the flexible elastic film 25 is sealed to the surface of the cover plate 2 facing the back plate 1, so that an air passage space 26 is formed between the flexible elastic film 25 and the cover plate 2. In each pair of corresponding flexible elastic films 25 and receiving cavities 11, the orthographic projection of the flexible elastic film 25 on the back plate 1 covers the detection chip unit 12 in the receiving cavity 11, and the orthographic projection of the liquid inlet 21 and the liquid outlet 22 of the receiving cavity 11 on the back plate 1 does not overlap with the orthographic projection of the air passage space 26 on the back plate 1. Specifically, the orthographic projection of the liquid inlet 21 on the back plate 1 is located on one side of the orthographic projection of the air passage space 26 on the back plate 1, and the orthographic projection of the liquid outlet 22 on the back plate 1 is located on the other side of the orthographic projection of the air passage space 26 on the back plate 1.

[0098] The cover plate 2 is provided with an air inlet 23 and an air outlet 24 that are both through the thickness direction of the cover plate 2 in the area forming the air passage space 26. The air inlet 23 and the air outlet 24 are only connected to the air passage space 26 so that when gas is filled from the air inlet 23, the flexible elastic film 25 deforms and covers each reaction chamber 120 of the detection chip unit 12.

[0099] In the detection system provided by the above technical solution, when using the detection system provided in the embodiments of the present invention, such as Figure 21 and Figure 22 As shown, Figure 21 The dashed arrow indicates the flow direction of the sample liquid. First, close the air inlet 23 and air outlet 24, then inject the sample liquid into the receiving cavity 11 through the liquid inlet 21 until the sample liquid fills the entire reaction chamber 11 and fully contacts the several reaction chambers 120 of the detection chip unit 12; then... Figure 22 As shown, by opening the air inlet 23 and closing the air outlet 24, gas at a certain pressure enters the gas path space 26 from the air inlet 23, applying pressure to the flexible elastic membrane 25 to deform it. At the same time, excess sample liquid is released from the liquid outlet 22 until the flexible elastic membrane 25 completely covers each reaction chamber 120 of the detection chip unit 12. Due to capillary action, the sample liquid in each reaction chamber 120 will not flow out, thereby dividing each reaction chamber 120, improving the effectiveness, stability and flexibility of the division of the reaction chamber 120, and making the operation simpler, realizing stable, sensitive and non-invasive detection of sample liquid.

[0100] For details, please continue to refer to Figure 21 and Figure 22 In each receiving cavity 11, the orthographic projections of the air inlet 23 and air outlet 24 on the cover plate 2 onto the back plate 1 do not overlap with the orthographic projection of the detection chip unit 12 onto the back plate 1. Specifically, the orthographic projection of the air inlet 23 onto the back plate 1 is located on one side of the orthographic projection of the detection chip unit 12 onto the back plate 1, and the orthographic projection of the air outlet 24 onto the back plate 1 is located on the other side of the orthographic projection of the detection chip unit 12 onto the back plate 1.

[0101] In one alternative embodiment, the edge of the flexible elastic film 25 is bonded to the surface of the cover plate 2 facing the back plate 1.

[0102] Specifically, the thickness of the flexible elastic film 25 is 5μm-90μm.

[0103] The flexible elastic film 25 can be deformed under a given pressure and can cover the reaction chamber 120. The flexible elastic film 25 should have elastic deformability and follow Huke's law (σ=E*ε and σ=P*S; σ is stress, E is elastic modulus / Young's modulus, ε is strain, P is gas pressure, and S is the area of ​​the flexible elastic film 25). Specifically, the material of the flexible elastic film 25 can be polydimethylsiloxane.

[0104] like Figure 21 and Figure 22As shown, in order to facilitate the formation of the air passage space 26, the part of the cover plate 2 used to form the air passage space 26 forms an inflation groove on the surface of the back plate 1. The flexible elastic film 25 covers the opening of the inflation groove, and the orthographic projection of the air inlet 23 and the air outlet 24 on the back plate 1 is located within the orthographic projection of the inflation groove on the back plate 1.

[0105] Specifically, the orthogonal projection of the inflation slot on the back plate 1 covers the orthogonal projection of the detection chip unit 12 on the back plate, and the orthogonal projection of the flexible elastic film 25 on the back plate 1 covers the orthogonal projection of the inflation slot on the back plate 1.

[0106] like Figure 21 and Figure 22 As shown, in each receiving cavity 11, the projection of the inflation groove on the back plate 1 covers each reaction chamber 120 of the detection chip unit 12 within the receiving cavity 11.

[0107] Preferably, the depth of the air-filled groove is 20μm-1000μm along the direction perpendicular to the cover plate 2.

[0108] Obviously, those skilled in the art can make various modifications and variations to the embodiments of the present invention without departing from the spirit and scope of the invention. Therefore, if these modifications and variations fall within the scope of the claims of the present invention and their equivalents, the present invention also intends to include these modifications and variations.

Claims

1. A high-throughput detection chip, characterized in that, include: Backplate, cover plate, and connectors; among which: The back plate and the cover plate are disposed opposite to each other, and the back plate and the cover plate are connected to form a plurality of receiving cavities; the back plate is provided with a detection chip unit corresponding to each receiving cavity on the side facing the cover plate, and each detection chip unit is located in the corresponding receiving cavity; each receiving cavity is provided with a liquid inlet and a liquid outlet; The connector includes pipes that correspond one-to-one with the receiving cavities. Each pipe is provided with a valve structure for controlling the opening and closing of the pipe. In each pair of corresponding pipes and receiving cavities, the inlet of the pipe is connected to the outlet of the receiving cavity. Multiple pipes form at least one pipe group. Each pipe group includes at least two pipes. The pipes in each pipe group share a sample liquid outlet. The back plate and the cover plate are connected by a sealing adhesive layer, and the receiving cavity is divided by the sealing adhesive layer; a first groove is formed on the surface of the sealing adhesive layer away from the back plate. The first groove has a bottom and two opposite sidewalls and an opening on one side facing the cover plate. The cover plate covers the first groove, and the surface of the cover plate facing the back plate cooperates with the first groove to form the conduit of the connector. One end of the conduit communicates with the receiving cavity to form the liquid outlet of the receiving cavity, and the cover plate is provided with sample liquid outlets corresponding one-to-one with the conduit assembly.

2. The high-throughput detection chip according to claim 1, characterized in that, The liquid outlet of the receiving cavity is formed in the cover plate, the pipes in the connector are connecting pipes, and each of the connecting pipes is located on the side of the cover plate away from the back plate.

3. The high-throughput detection chip according to claim 1, characterized in that, The valve structure includes a pneumatic valve.

4. The high-throughput detection chip according to claim 3, characterized in that, In each pair of corresponding air valves and pipelines: The air valve includes an elastic valve plate, the edge of which is sealed to the cover plate to form an air-controlled chamber. The elastic valve plate covers the first groove along the arrangement direction of the two side walls, with its orthogonal projection on the sealing frame adhesive layer. The cover plate has a through hole that communicates with the air-controlled chamber and is configured as an air-controlled inlet. When a set pressure gas is introduced into the air-controlled chamber from the air-controlled inlet, the elastic valve plate deforms and extends into the first groove, fitting against the bottom of the first groove and the two side walls.

5. The high-throughput detection chip according to claim 4, characterized in that, In each pair of corresponding air valves and pipelines, the air control inlet does not overlap between the orthographic projection of the back plate and the orthographic projection of the first groove on the back plate.

6. The high-throughput detection chip according to claim 1, characterized in that, The back plate has a slot formed on the surface facing the cover plate for at least one of the back plates, and the detection chip unit is installed in the slot.

7. The high-throughput detection chip according to claim 1, characterized in that, The detection chip unit is formed on the surface of the backplate facing the cover plate.

8. The high-throughput detection chip according to claim 1, characterized in that, The cover plate has a flexible elastic film on the side facing the back plate that corresponds to each of the receiving cavities. The flexible elastic film is located inside the receiving cavity, and the edge of the flexible elastic film is sealed to the surface of the cover plate facing the back plate, so that an air passage space is formed between the flexible elastic film and the cover plate. In each pair of corresponding flexible elastic films and receiving cavities, the orthographic projection of the flexible elastic film on the back plate covers the detection chip unit in the receiving cavity, and there is no overlap between the orthographic projection of the liquid inlet and liquid outlet of the receiving cavity on the back plate and the orthographic projection of the air passage space on the back plate. The cover plate is provided with an air inlet and an air outlet in the area forming the gas passage space, both extending along its own thickness direction. The air inlet and the air outlet are only connected to the gas passage space, so that when gas is filled from the air inlet, the flexible elastic film deforms and covers each reaction chamber of the detection chip unit.

9. The high-throughput detection chip according to claim 8, characterized in that, In each of the accommodating cavities, the air inlet and air outlet provided on the cover plate do not overlap with the orthographic projection of the detection chip unit on the back plate.

10. The high-throughput detection chip according to claim 8, characterized in that, The edge of the flexible elastic film is bonded to the surface of the cover plate facing the back plate.

11. The high-throughput detection chip according to claim 8, characterized in that, The thickness of the flexible elastic film is 5μm-90μm.

12. The high-throughput detection chip according to claim 8, characterized in that, The portion of the cover plate used to form the air passage space forms an inflation groove on the surface facing the back plate. The flexible elastic film covers the opening of the inflation groove, and the orthographic projections of the air inlet and the air outlet on the back plate are located within the orthographic projection of the inflation groove on the back plate.

13. The high-throughput detection chip according to claim 12, characterized in that, In each of the aforementioned receiving cavities, the projection of the inflation groove onto the back plate covers each reaction chamber of the detection chip unit within the receiving cavity.

14. The high-throughput detection chip according to claim 12 or 13, characterized in that, The depth of the air-filled groove is 20μm-1000μm along the direction perpendicular to the cover plate.

15. The high-throughput detection chip according to claim 6, characterized in that, Several card slots are arranged in an array.

16. The high-throughput detection chip according to claim 6, characterized in that, Several slots are arranged in a ring around the sample liquid outlet of the connector.

17. The high-throughput detection chip according to claim 8, characterized in that, The detection chip unit also includes a temperature control layer; the temperature control layer is disposed on the back plate and is used to heat several reaction chambers.

18. The high-throughput detection chip according to claim 17, characterized in that, The detection chip unit also includes a voltage control unit, which is electrically connected to the temperature control layer.

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