Microfluidic chip and marking device

Abstract

The application discloses a micro-fluidic chip and a marking device. The micro-fluidic chip comprises a flow channel chip and a cover plate. The flow channel chip comprises a marking area for marking cell tissues. The surface of the flow channel chip is provided with a plurality of grooves. The plurality of grooves pass through the marking area. The plurality of grooves located in the marking area are arranged in parallel and at intervals along a first direction. The lengths of the plurality of grooves are the same. The cover plate is used for carrying cell tissues. The cover plate is covered on the surface of the flow channel chip provided with the grooves so that the cell tissues overlap with the marking area. The cover plate is provided with a plurality of through holes penetrating the surface of the cover plate. The through holes are in one-to-one correspondence with the inlets and outlets of the grooves and are in communication with the inlets and outlets. The through holes provided on the cover plate can improve the efficiency of arranging the inlets and outlets of the marking flow channels, avoid burr problems caused by punching on the flow channel chip, and improve the adhesion and sealing effect between the flow channel chip and the cover plate.

Description

Technical Field

[0001] This application relates to the field of space multi-omics technology, and in particular to a microfluidic chip and labeling device. Background Technology

[0002] Spatial multi-omics technology based on microfluidics involves adding markers to molecules within tissue slide cells using a microfluidic chip with multiple lateral channels, thereby forming at least one-dimensional encoding of the spatial coordinates of intracellular molecules. Similarly, by adding a second round of markers along the longitudinal direction, the intersection of the two marking directions enables two-dimensional encoding of the spatial positions of intracellular molecules.

[0003] In related technologies, microfluidic chips with the aforementioned flow channels require manual drilling at the beginning and end of each channel. The through-hole at the channel's beginning serves as the inlet for adding markers, while the through-hole at the end serves as the outlet for negative pressure to draw the markers. However, this presents several drawbacks. First, the large number of holes on the microfluidic chip and the tendency for burrs to form at the edges of the holes negatively impact the sealing effect of subsequent operations and hinder drilling efficiency. Second, the multiple flow channels within the microfluidic chip for marker addition can lead to differences in flow resistance between channels, making it difficult to add markers evenly and affecting the marking effect. Utility Model Content

[0004] To solve at least one of the above-mentioned technical problems, this application provides a microfluidic chip and a labeling device, and the technical solution adopted is as follows.

[0005] The microfluidic chip provided by the first party in this application includes a flow channel chip and a cover plate. The flow channel chip includes a marking area for marking cells and tissues. The surface of the flow channel chip is provided with multiple grooves, all of which pass through the marking area. The multiple grooves located in the marking area are arranged parallel to each other along a first direction and have the same length. The cover plate is used to hold the cells and tissues. The cover plate covers the surface of the flow channel chip with the grooves so that the cells and tissues overlap with the marking area. The cover plate is provided with multiple through holes penetrating the surface of the cover plate, and the through holes are connected to the inlet and outlet of the grooves one by one.

[0006] In some embodiments of this application, the flow channel chip further includes an inlet area and an outlet area, the inlet area and the outlet area being located on opposite sides of the marking area, the inlet of the groove being disposed in the inlet area, the outlet of the groove being disposed in the outlet area, and the through hole being disposed in the inlet area and the outlet area.

[0007] In some embodiments of this application, the portions of the groove located in the liquid inlet area and the liquid outlet area are symmetrically arranged with respect to the marking area.

[0008] In some embodiments of this application, the interval between two adjacent grooves in the liquid inlet area along a first direction is greater than the interval in the marking area, and the interval between adjacent grooves gradually increases from the marking area to the liquid inlet area.

[0009] In some embodiments of this application, the interval between two adjacent grooves in the liquid outlet area along a first direction is greater than the interval in the marking area, and the interval between adjacent grooves gradually increases from the marking area to the liquid outlet area.

[0010] In some embodiments of this application, the flow channel chip includes a first chip and a second chip, wherein the first chip is used to mark samples along a first direction of the first chip, and the second chip is used to mark samples along a first direction of the second chip, wherein the first direction of the first chip and the first direction of the second chip are perpendicular to each other.

[0011] In some embodiments of this application, the first chip further includes a liquid inlet area and a liquid outlet area, the inlet of the groove is disposed in the liquid inlet area, the outlet of the groove is disposed in the liquid outlet area, the through hole is disposed in the liquid inlet area and the liquid outlet area, and the line connecting the liquid inlet area and the liquid outlet area is parallel to the extension direction of the groove in the marking area;

[0012] The first chip includes a plurality of groove groups, each groove group including a plurality of grooves. The plurality of groove groups are spaced apart in the liquid inlet area along a first direction. The inlets of the plurality of grooves in the same groove group are spaced apart in a second direction. The plurality of groove groups are spaced apart in the liquid outlet area along a first direction. The outlets of the plurality of grooves in the same groove group are spaced apart in a second direction.

[0013] Wherein, the first direction and the second direction are perpendicular to each other.

[0014] In some embodiments of this application, the second chip further includes a liquid inlet area and a liquid outlet area, the inlet of the groove is disposed in the liquid inlet area, the outlet of the groove is disposed in the liquid outlet area, the through hole is disposed in the liquid inlet area and the liquid outlet area, and the line direction connecting the liquid inlet area and the liquid outlet area is perpendicular to the extension direction of the groove in the marking area.

[0015] Multiple groove groups are spaced apart in the liquid inlet area along a second direction, the inlets of multiple grooves in the same groove group are spaced apart in a first direction, the multiple groove groups are spaced apart in the liquid outlet area along a second direction, and the outlets of multiple grooves in the same groove group are spaced apart in a first direction.

[0016] Wherein, the first direction and the second direction are perpendicular to each other.

[0017] In some embodiments of this application, multiple groove groups are equally spaced, and the inlets of multiple grooves located in the same groove group are equally spaced, so that the inlets of multiple grooves are arrayed in the liquid inlet area.

[0018] In some embodiments of this application, multiple groove groups are equally spaced, the outlets of multiple grooves located in the same groove group are equally spaced, and the outlets of multiple grooves are arranged in an array in the liquid outlet area.

[0019] In some embodiments of this application, the diameter of the through hole decreases in the direction of the groove.

[0020] In some embodiments of this application, the cover plate is a glass sheet, and the through hole is formed by laser drilling.

[0021] In some embodiments of this application, the through hole is configured as a stepped hole, wherein the diameter of the through hole at the end near the groove is smaller than the diameter at the end away from the groove.

[0022] In some embodiments of this application, the through hole is configured as a tapered hole, and the diameter of the through hole gradually decreases toward the end near the groove.

[0023] In some embodiments of this application, the cover plate includes a protrusion that protrudes beyond the sidewall of the channel chip when the cover plate is closed on the channel chip.

[0024] In some embodiments of this application, the cover plate is separable from the flow channel chip. When cell tissue is added to the surface of the cover plate, the cover plate is separated from the flow channel chip. When the cover plate is connected to the flow channel chip, the surface of the cover plate with cell tissue is attached to the surface of the flow channel chip with the groove.

[0025] Secondly, this application provides a marking device, including a negative pressure structure and a microfluidic chip provided in the first aspect, wherein the negative pressure structure is connected to the outlet of the groove.

[0026] The embodiments of this application have at least the following beneficial effects: Utilizing the capping action of the cover plate and the flow channel chip, the cells to be labeled can be clamped between the cover plate and the flow channel chip, placing the cells in the labeling area. By providing grooves on the surface of the flow channel chip, the marker can flow along the grooves. When the marker flows through the labeling area, it can combine with the cells to be labeled and complete the labeling. By setting each groove to have the same length, the flow resistance in each groove can be approximately the same, allowing the marker to be added evenly in each groove. This ensures that the cells to be labeled at each position in the labeling area can fully combine with the marker, improving the labeling effect and meeting experimental requirements. By setting through holes on the cover plate and utilizing the sealing effect of the cover plate and the flow channel chip, each groove can form an independent marking flow channel, and the through holes of the cover plate can form the inlet and outlet of each marking flow channel. This avoids the manual drilling operation on the flow channel chip. In this way, the flow channel chip and the cover plate can be processed separately. The through holes on the cover plate can be directly stamped, machined, or laser-cut. On the one hand, it improves the efficiency of setting the inlet and outlet of each marking flow channel, and on the other hand, it avoids the burr problem caused by manual drilling on the flow channel chip, improves the fit between the flow channel chip and the cover plate, and ensures a good sealing effect when the flow channel chip and the cover plate are closed together. Attached Figure Description

[0027] The present application will be further illustrated below with reference to the accompanying drawings and embodiments. It should be noted that the embodiments illustrated in the following drawings are exemplary and are only used to explain the present application, and should not be construed as limiting the present application.

[0028] Figure 1 This is a schematic diagram of the structure of the microfluidic chip provided in the embodiments of this application;

[0029] Figure 2 for Figure 1 AA cross-section view;

[0030] Figure 3 This is a schematic diagram of the structure of the first chip of the microfluidic chip provided in the embodiments of this application;

[0031] Figure 4 This is a schematic diagram of the structure of the second chip of the microfluidic chip provided in the embodiments of this application;

[0032] Figure 5 This is a partial enlarged view of the marking area of ​​the microfluidic chip provided in the embodiments of this application;

[0033] Figure 6 A schematic diagram of the cover plate of the microfluidic chip provided in the embodiments of this application;

[0034] Figure 7 for Figure 6 A magnified view of section B.

[0035] Reference numerals: 100, microfluidic chip; 10, flow channel chip; 11, marking area; 12, groove; 13, liquid inlet area; 14, liquid outlet area; 15, first chip; 151, groove group; 16, second chip; 161, groove group; 20, cover plate; 21, through hole; 22, protrusion. Detailed Implementation

[0036] The embodiments of this application are described in detail below with reference to the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0037] In the description of this application, it should be understood that the terms "center", "middle", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, are only for the convenience of describing this application 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, and therefore should not be construed as a limitation of this application.

[0038] In the description of this application, "several" means one or more, "multiple" means two or more, "greater than," "less than," and "exceeding" are understood to exclude the stated number, while "above," "below," and "within" are understood to include the stated number. The use of "first" and "second" in the description is merely for distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of indicated technical features, or implicitly indicating the order of the indicated technical features.

[0039] In the description of this application, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; 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; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0040] In the description of this application, the use of terms such as "as one implementation," "an embodiment," "some examples," "some embodiments," "illustrative embodiment," "example," "specific example," "some examples," etc., indicates that the specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0041] Firstly, please refer to Figures 1 to 4 This application proposes a microfluidic chip 100, including a channel chip 10 and a cover plate 20. The channel chip 10 includes a labeling region 11 for labeling cells and tissues. The surface of the channel chip 10 is provided with multiple grooves 12, all of which pass through the labeling region 11. The multiple grooves 12 located in the labeling region 11 are arranged parallel to each other along a first direction x, and the length of the multiple grooves 12 is the same. The cover plate 20 is used to hold the cells and tissues. The cover plate 20 covers the surface of the channel chip 10 with the grooves 12, so that the cells and tissues overlap with the labeling region 11. The cover plate 20 is provided with multiple through holes 21 penetrating the surface of the cover plate 20, and the through holes 21 are connected to the inlet and outlet of the grooves 12 one by one.

[0042] When labeling cell tissue, the cell tissue to be labeled is first fixed on the surface of the cover plate 20. Next, the surface of the cover plate 20 with the fixed cell tissue is placed over the surface of the flow channel chip 10 with grooves 12, allowing the cell tissue to overlap with the labeling area 11. The covering action of the cover plate 20 and the flow channel chip 10 clamps the cell tissue to be labeled between them, placing it within the labeling area 11. Since the marker flows along the grooves 12, it binds to the cell tissue as it flows through the labeling area 11, completing the labeling process. By setting each groove 12 to have the same length, the flow resistance in each groove 12 is approximately the same, ensuring that the marker is added evenly to each groove 12. This guarantees that the cell tissue at each location in the labeling area 11 can fully bind with the marker, improving the labeling effect and meeting experimental requirements. By setting the through hole 21 on the cover plate 20 and utilizing the sealing effect of the cover plate 20 and the flow channel chip 10, each groove 12 can form an independent marking flow channel. That is, the marking flow channel can achieve the effect of sealing from top to bottom and is isolated from adjacent marking flow channels. Furthermore, the through hole 21 of the cover plate 20 can form the inlet and outlet of each marking flow channel, avoiding the manual drilling operation on the flow channel chip 10. In this way, the flow channel chip 10 and the cover plate 20 can be processed separately. The through hole 21 on the cover plate 20 can be directly stamped, machined, or laser-cut. On the one hand, it improves the efficiency of setting the inlet and outlet of each marking flow channel, and on the other hand, it avoids the burr problem caused by manual drilling on the flow channel chip 10, improves the fit between the flow channel chip 10 and the cover plate 20, and ensures a good sealing effect when the flow channel chip 10 and the cover plate 20 are covered together.

[0043] When labeling cellular tissues, labeling is typically performed in two mutually angular (e.g., perpendicular) directions. This allows the tissue to be labeled to achieve labeling effects in two dimensions (e.g., horizontal and vertical). Combining these two-dimensional labeling methods enables more precise tissue labeling. Therefore, in some embodiments, the flow channel chip 10 includes a first chip 15 and a second chip 16. The first chip 15 is used to label samples along a first direction x, and the second chip 16 is used to label samples along a first direction x. The first direction x of the first chip 15 and the first direction x of the second chip 16 are perpendicular to each other. By setting the first chip 15 and the second chip 16, each chip has a first direction x, and the first directions x of the two chips are perpendicular to each other. Thus, by sequentially labeling the tissue with the first chip 15 and the second chip 16, labeling effects in two perpendicular directions can be obtained. Using the two sets of labeling information, a single labeling point can be uniquely determined on a plane. That is, the labeling effect of the first chip 15 and the second chip 16 can serve as the planar coordinates of any point on the tissue to be labeled, achieving precise tissue labeling. It is understandable that during the experimental operation, the first chip 15 and the second chip 16 need to be combined with the cover plate 20 containing the same cell tissue and marked in turn. The order of implementation of the first chip 15 and the second chip 16 is not limited here.

[0044] In some embodiments, the cover plate 20 is a glass sheet, and the through hole 21 can be formed by laser drilling of the glass. On the one hand, laser drilling can be completed using an automated process, avoiding manual drilling of the flow channel chip 10, thereby improving the forming efficiency of the through hole 21. On the other hand, laser drilling helps to improve the smoothness of the edge of the through hole 21, solving the problem of burrs on the edge of the through hole caused by manual drilling.

[0045] In some embodiments, the flow channel chip 10 further includes an inlet region 13 and an outlet region 14, which are located on opposite sides of the marking region 11. The inlet of the groove 12 is located in the inlet region 13, and the outlet of the groove 12 is located in the outlet region 14. A through hole 21 is located in both the inlet region 13 and the outlet region 14. The inlet region 13 and the outlet region 14 enable the flow channel chip 10 to perform both inlet and outlet functions. Utilizing the inlet of the groove 12 in the inlet region 13 and the outlet of the groove 12 in the outlet region 14, when the cover plate 20 seals the flow channel chip 10, the groove 12 forms a marking channel. A marker can be added to the marking channel from the inlet region 13, and negative pressure is applied to the marking channel from the outlet region 14, guiding the marker to flow along the marking channel and through the cell tissue to be marked in the marking region 11, thereby binding with the cell tissue to achieve marking. The inlet of the groove 12 is concentrated in the liquid inlet area 13, and the outlet is concentrated in the liquid outlet area 14, which can improve the compactness of the flow channel chip 10. By setting the liquid inlet area 13 and the liquid outlet area 14 on both sides of the marking area 11, the spatial arrangement of the flow channel chip 10 can be more reasonable, and the structure of the flow channel chip 10 can be more compact.

[0046] In some embodiments, the portions of the groove 12 located in the inlet region 13 and the outlet region 14 are symmetrically arranged with respect to the marking region 11. This allows the groove 12 to have the same structure in both the inlet region 13 and the outlet region 14, eliminating the need to distinguish between the inlet region 13 and the outlet region 14 when using the flow channel chip 10. In other words, the inlet region 13 and the outlet region 14 can be used interchangeably, improving the ease of use of the flow channel chip 10. Furthermore, by symmetrically arranging the beginning and end of the groove 12, it is helpful to control the length of each groove 12, ensuring that each groove 12 has the same length. This reduces the flow resistance differences in each marking channel, achieving the effect that the flow velocity of the marker is approximately the same in each marking channel.

[0047] In some embodiments, the spacing between two adjacent grooves 12 in the liquid inlet area 13 is greater than the spacing in the marking area 11. From the marking area 11 to the liquid inlet area 13, the spacing between adjacent grooves 12 gradually increases along the first direction x. Within the liquid inlet area 13, a larger spacing between two adjacent grooves 12 provides sufficient space for labeling operations, improving operational convenience. Conversely, a smaller spacing between the grooves 12 in the marking area 11 increases the density of the grooves 12, making them more compact and helping to adapt the size of the marking area 11 to the size of the cell tissue slice, while also meeting the labeling density requirements. The gradually increasing spacing between adjacent grooves 12 along the path from the liquid inlet area 13 to the marking area 11 satisfies the varying spacing requirements of the grooves 12 in both the liquid inlet area 13 and the marking area 11.

[0048] Similarly, the outlet zone 14 can also adopt the same configuration, and its effect is similar to that of the inlet zone 13. In some embodiments, the distance between two adjacent grooves 12 in the outlet zone 14 along the first direction x is greater than the distance in the marking zone 11, and the distance between adjacent grooves 12 gradually increases from the marking zone 11 to the outlet zone 14. In this way, within the outlet zone 14, there is a large distance between the grooves 12, which facilitates the negative pressure suction device to perform negative pressure suction on the outlet of the groove 12, improving the convenience of experimental operation.

[0049] Understandably, please refer to Figure 5 The marking area 11 includes multiple grooves 12, which are closely arranged within the marking area 11. The multiple grooves 12 remain independent of each other within the marking area 11, thereby ensuring that different added markers can flow independently in multiple grooves 12, and that each groove 12 does not communicate with each other, thus avoiding confusion or interference between markers in different grooves 12.

[0050] In some embodiments, the first chip 15 further includes an inlet region 13 and an outlet region 14. The inlet of the groove 12 is disposed in the inlet region 13, and the outlet of the groove 12 is disposed in the outlet region 14. A through hole 21 is disposed in the inlet region 13 and the outlet region 14. The line connecting the inlet region 13 and the outlet region 14 is parallel to the extension direction of the groove 12 in the marking region 11. The first chip 15 includes a plurality of groove groups 151, each groove group 151 including a plurality of grooves 12. The plurality of groove groups 151 are spaced apart in the inlet region 13 along a first direction x. The inlets of the plurality of grooves 12 in the same groove group 151 are spaced apart along a second direction y. The plurality of groove groups 151 are spaced apart in the outlet region 14 along the first direction x. The outlets of the plurality of grooves 12 in the same groove group 151 are spaced apart along the second direction y. The first direction x and the second direction y are perpendicular to each other.

[0051] Regarding the first chip 15, this arrangement allows for the grouping of multiple grooves 12, ensuring an orderly arrangement of the grooves 12 in both the inlet and outlet areas 13 and 14, thus improving the orderliness of the groove arrangement. Furthermore, it allows for the arraying of the inlets and outlets of the grooves 12, shortening the distance between multiple inlets (or outlets) and making the structure of the first chip 15 more compact. Since the number of inlets and outlets of the grooves 12 is always the same, the inlet is used as an example for explanation. For instance, using... Figure 3For example, the first chip 15 has 56 grooves 12, and correspondingly, each groove 12 has 56 inlets. Compared to arranging these inlets in a straight line, arranging them in an array, such as an 8*7 array, can shorten the size of the liquid inlet area 13 in the x-direction, thus facilitating the operation of adding markers to the first chip 15. For example, a 4-row automatic pipette can be used for intermittent sample addition. The array-style arrangement of the grooves 12 inlets helps to reduce the difficulty of sample addition operations and the risk of operational errors (repeated addition or omission).

[0052] A similar arrangement can be used for the second chip 16, the difference being that the first direction x in the second chip 16 is perpendicular to the first direction x in the first chip 15. That is, the direction of the groove 12 in the marking area 11 of the first chip 15 is perpendicular to the direction in the second chip 16. This allows for marking effects in two mutually perpendicular directions by using the first chip 15 and the second chip 16 respectively. Therefore, in some embodiments, the second chip 16 further includes a liquid inlet area 13 and a liquid outlet area 14. The inlet of the groove 12 is located in the liquid inlet area 13, and the outlet of the groove 12 is located in the liquid outlet area 14. The through hole 21 is located in the liquid inlet area 13 and the liquid outlet area 14. The line connecting the liquid inlet area 13 and the liquid outlet area 14 is perpendicular to the extension direction of the groove 12 in the marking area 11. Multiple groove groups 161 are spaced apart along the second direction y in the liquid inlet area 13. The inlets of multiple grooves 12 within the same groove group 161 are spaced apart along the first direction x. Multiple groove groups 161 are spaced apart along the second direction y in the liquid outlet area 14. The outlets of multiple grooves 12 within the same groove group 161 are spaced apart along the first direction x. The first direction x and the second direction y are perpendicular to each other. Therefore, in the second chip 16, the inlets of the grooves 12 in the liquid inlet area 13 and the outlets in the liquid outlet area 14 are also arranged in an array, which helps to achieve an orderly arrangement of the inlets and outlets.

[0053] Optionally, the grooves 12 of the first chip 15 and the grooves 12 of the second chip 16 are arranged in the same way at the inlet of the liquid inlet area 13, and the grooves 12 are arranged in the same way at the outlet of the liquid outlet area 14. In this way, the cover plate 20 adapted to the first chip 15 can be used in the second chip 16. This means that the cover plate 20 of the same size can be adapted to both the first chip 15 and the second chip 16, thereby improving the versatility of the components of the microfluidic chip 100.

[0054] In some embodiments, multiple groove groups 151, 161 are equally spaced, and the inlets of multiple grooves 12 located in the same groove group 151, 161 are equally spaced, so that the inlets of the multiple grooves 12 are arrayed in the liquid inlet area 13. By controlling the spacing between the inlets of the grooves 12 to be the same, it is helpful to adapt to multi-row automatic pipettes and improve the convenience of experimental operations.

[0055] Similarly, the same arrangement can be used at the outlet of the groove 12. Therefore, in some embodiments, multiple groove groups 151 and 161 are arranged at equal intervals, the outlets of multiple grooves 12 located in the same groove group 151 and 161 are arranged at equal intervals, and the outlets of multiple grooves 12 are arranged in an array in the liquid outlet area 14.

[0056] To ensure that markers can be successfully added to the marker channel, please refer to [link / reference]. Figure 6 and Figure 7 Therefore, in some embodiments, the diameter of the through-hole 21 decreases towards the groove 12. This allows the through-hole 21 to have a "larger at the top and smaller at the bottom" structure. This structure increases the liquid storage capacity of the through-hole 21, ensuring that sufficient markers can be added by storing them in each through-hole 21. Furthermore, the markers can flow smoothly into the groove 12 via the gradually decreasing diameter of the through-hole 21, improving the smoothness of the marker dripping into the groove 12.

[0057] In some embodiments, the through hole 21 is configured as a stepped hole (e.g., Figure 6 , Figure 7 As shown, the diameter of the through hole 21 at the end near the groove 12 is smaller than the diameter at the end away from the groove 12. A stepped hole means that the through hole 21 has at least two sections with different diameters; the section with the larger diameter is used to store the marker liquid, and the section with the smaller diameter connects to the groove 12 for introducing the marker into the groove 12. Stepped holes are also easy to manufacture, making them readily achievable.

[0058] Of course, in other examples, the through hole 21 can also be set as a tapered hole, with the diameter of the through hole 21 gradually decreasing towards the end near the groove 12.

[0059] In some embodiments, the cover plate 20 includes a protrusion 22, which protrudes from the sidewall of the channel chip 10 when the cover plate 20 is closed onto the channel chip 10. Since the cover plate 20 and the channel chip 10 have a sealing effect after being closed together, i.e., a certain surface tension keeps the cover plate 20 and the channel chip 10 in close contact, this makes it difficult for the cover plate 20 to be separated from the channel chip 10. Therefore, by providing the protrusion 22, when it is necessary to separate the cover plate 20 from the channel chip 10, force can be applied using the protrusion 22 to lift the cover plate 20 from the channel chip 10, so as to separate it from the channel chip 10. Exemplarily, the protrusion 22 can be any one or more sidewalls of the upper cover plate 20 (e.g., Figure 1 As shown, this side protrudes from the sidewall of the flow channel chip 10. Alternatively, in other examples, the protrusion may be a block-shaped structure protruding from the sidewall of the flow channel chip 10 at any position on the cover plate 20.

[0060] Secondly, this application also provides a labeling device, which includes a negative pressure structure and the microfluidic chip 100 provided in the first aspect. The negative pressure structure is connected to the outlet of the groove 12. By utilizing the negative pressure structure connected to the outlet of the groove 12, a negative pressure attraction effect can be formed on the labeling channel, thereby attracting the labeled material to flow from the inlet to the outlet. During this process, the material passes through the labeling area of ​​the groove 12 and combines with cell tissue to achieve labeling. The negative pressure structure can be a vacuum pump or other similar device, and is not limited here.

[0061] In some embodiments, the labeling device may further include a positive pressure structure, such as an air pump. The positive pressure structure may be connected to the inlet of the groove 12. By applying positive pressure to the groove 12, a positive pressure pushing effect is formed in the labeling channel, which pushes the label to flow in the labeling channel. During this process, the label passes through the labeling area 11 and binds to the cell tissue to achieve labeling.

[0062] The embodiments of this application have been described in detail above with reference to the accompanying drawings. However, this application is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of this application. Furthermore, unless otherwise specified, the embodiments and features described in the embodiments of this application can be combined with each other.

Claims

1. A microfluidic chip, characterized by: include A flow channel chip, the flow channel chip including a marking area for marking cell tissue, the surface of the flow channel chip having a plurality of grooves, the plurality of grooves passing through the marking area, the plurality of grooves located in the marking area being arranged parallel to each other along a first direction, and the plurality of grooves having the same length; A cover plate is used to support cell tissue. The cover plate is sealed on the surface of the flow channel chip with the groove so that the cell tissue overlaps with the marking area. The cover plate has a plurality of through holes penetrating the surface of the cover plate, and the through holes are connected to the inlet and outlet of the groove one by one.

2. The microfluidic chip of claim 1, wherein: The flow channel chip further includes a liquid inlet area and a liquid outlet area, which are located on both sides of the marking area. The inlet of the groove is located in the liquid inlet area, the outlet of the groove is located in the liquid outlet area, and the through hole is located in the liquid inlet area and the liquid outlet area.

3. The microfluidic chip of claim 2, wherein: The portions of the groove located in the liquid inlet area and the liquid outlet area are symmetrically arranged about the marking area.

4. The microfluidic chip of claim 2, wherein: The distance between two adjacent grooves in the liquid inlet area along the first direction is greater than the distance in the marking area, and the distance between adjacent grooves gradually increases from the marking area to the liquid inlet area.

5. The microfluidic chip of claim 2, wherein: The distance between two adjacent grooves in the liquid outlet area along the first direction is greater than the distance in the marking area, and the distance between adjacent grooves gradually increases from the marking area to the liquid outlet area.

6. The microfluidic chip of claim 1, wherein: The flow channel chip includes a first chip and a second chip. The first chip is used to mark samples along a first direction of the first chip, and the second chip is used to mark samples along a first direction of the second chip. The first direction of the first chip and the first direction of the second chip are perpendicular to each other.

7. The microfluidic chip of claim 6, wherein: The first chip further includes a liquid inlet area and a liquid outlet area. The inlet of the groove is disposed in the liquid inlet area, the outlet of the groove is disposed in the liquid outlet area, the through hole is disposed in the liquid inlet area and the liquid outlet area, and the line connecting the liquid inlet area and the liquid outlet area is parallel to the extension direction of the groove in the marking area. The first chip includes a plurality of groove groups, each groove group including a plurality of grooves. The plurality of groove groups are spaced apart in the liquid inlet area along a first direction. The inlets of the plurality of grooves in the same groove group are spaced apart in a second direction. The plurality of groove groups are spaced apart in the liquid outlet area along a first direction. The outlets of the plurality of grooves in the same groove group are spaced apart in a second direction. Wherein, the first direction and the second direction are perpendicular to each other.

8. The microfluidic chip of claim 6, wherein: The second chip further includes a liquid inlet area and a liquid outlet area. The inlet of the groove is located in the liquid inlet area, the outlet of the groove is located in the liquid outlet area, and the through hole is located in the liquid inlet area and the liquid outlet area. The line connecting the liquid inlet area and the liquid outlet area is perpendicular to the extension direction of the groove in the marking area. The plurality of groove groups are arranged at intervals along the second direction at the liquid inlet area, and the inlets of the plurality of grooves in the same groove group are arranged at intervals along the first direction. The plurality of groove groups are arranged at intervals along the second direction at the liquid outlet area, and the outlets of the plurality of grooves in the same groove group are arranged at intervals along the first direction. The first direction is perpendicular to the second direction.

9. The microfluidic chip according to claim 7 or 8, characterized in that: The plurality of groove groups are arranged at intervals, and the inlets of the plurality of grooves in the same groove group are arranged at intervals, so that the inlets of the plurality of grooves are arranged in an array at the liquid inlet area.

10. The microfluidic chip according to claim 7 or 8, characterized in that: The plurality of groove groups are arranged at intervals, and the outlets of the plurality of grooves in the same groove group are arranged at intervals, so that the outlets of the plurality of grooves are arranged in an array at the liquid outlet area.

11. The microfluidic chip according to any one of claims 1 to 8, wherein: The cover plate is a glass sheet, and the through hole is formed by laser drilling.

12. The microfluidic chip according to any one of claims 1 to 8, wherein: The aperture of the through hole decreases towards the groove.

13. The microfluidic chip of claim 12, wherein: The through hole is a stepped hole, and the aperture of the end of the through hole close to the groove is smaller than the aperture of the end of the through hole away from the groove.

14. The microfluidic chip of claim 12, wherein: The through hole is a tapered hole, and the aperture of the through hole gradually decreases towards the end close to the groove.

15. The microfluidic chip according to any one of claims 1 to 8, wherein: The cover plate includes a protruding portion, and when the cover plate covers the flow channel chip, the protruding portion protrudes from the side wall of the flow channel chip.

16. The microfluidic chip of claim 1, wherein: The cover plate is detachable from the flow channel chip, and the cover plate is detached from the flow channel chip when adding cell tissue to the surface of the cover plate. When the cover plate is connected to the flow channel chip, the surface of the cover plate provided with the cell tissue is attached to the surface of the flow channel chip provided with the groove.

17. A marking device characterized by: The microfluidic chip according to any one of claims 1 to 16, and a negative pressure structure connected to the outlet of the groove.

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