Microfluidic chip

Abstract

The embodiment of the utility model discloses a microfluidic chip, and relates to the technical field of microfluid. The microfluidic chip comprises a substrate and a base body, wherein the base body is arranged on the substrate; a flow channel is formed in the face, facing the base, of the base body. A plurality of grooves are formed in the face, facing the base body, of the base, and the grooves communicate with the flow channels. Wherein the groove is internally provided with a plurality of nanowires, the plurality of nanowires are arranged at intervals so as to divide the bottom of the groove into a plurality of sub-grooves, and the size of the groove is matched with the size of a cell to be captured. The size of the groove is designed to be matched with the size of the to-be-captured CTC, so that the CTC with larger volume can be effectively captured, and the retention of non-target cells (such as leukocytes) is reduced, thereby ensuring that the captured CTC has higher specificity, reducing the risk of false positive and being beneficial to improving the capturing efficiency.

Description

Technical Field

[0001] The present application relates to the field of microfluidics technology, and in particular to a microfluidic chip. Background Art

[0002] With the deepening of cancer research, the detection of circulating tumor cells (CTCs) has become an important tool in the field of liquid biopsy. Capturing CTCs from the blood through non-invasive methods can provide important tumor dynamics information. However, the current traditional CTC capture method is easily interfered by other cells, such as white blood cells, resulting in false positives in the detection and capture results. Utility Model Content

[0003] The embodiments of the present application provide a microfluidic chip to improve the problem of false capture and false positive results in traditional CTC capture methods.

[0004] In a first aspect, an embodiment of the present application provides a microfluidic chip, comprising a substrate and a base, wherein the base is disposed on the substrate; a flow channel is formed on a side of the base facing the substrate; a plurality of grooves are formed on a side of the base facing the substrate, wherein the grooves are connected to the flow channel;

[0005] Wherein, a plurality of nanowires are provided in the groove, and the plurality of nanowires are arranged at intervals to separate the bottom of the groove into a plurality of sub-grooves, and the size of the groove matches the size of the cells to be captured.

[0006] In some embodiments of the present application, the inner wall of the groove is hemispherical, and the groove is connected to the plane of the base in an arc shape.

[0007] In some embodiments of the present application, the maximum diameter of the groove ranges from 10um to 20um, and the maximum depth of the groove ranges from 5um to 15um.

[0008] In some embodiments of the present application, the inner wall of the groove includes multiple side walls and a bottom wall, multiple side walls are connected to the bottom wall and multiple side walls are arranged and connected in sequence along the circumferential direction of the bottom wall, and the end of the side wall facing away from the bottom wall is connected to the plane of the base in an arc shape.

[0009] In some embodiments of the present application, along the direction from the bottom wall toward the opening of the groove, the side wall is inclined toward a position away from the center of the groove, so that the groove is open.

[0010] In some embodiments of the present application, a plurality of the grooves are arranged in an array and each of the grooves is aligned and connected to the flow channel.

[0011] In some embodiments of the present application, the plurality of nanowires are vertically arranged along the inner wall of the groove, and the plurality of nanowires are arranged in a stepped manner, and the side of the nanowire at the highest height facing away from the bottom of the groove is no higher than the height of the plane of the substrate.

[0012] In some embodiments of the present application, the base is provided with a sample inlet and a sample outlet, the flow channel includes multiple sub-channels and connecting channels, the multiple sub-channels are arranged in an array, and two adjacent sub-channels are connected by the connecting channel. Along the direction of the array arrangement, the first sub-channel is connected to the sample inlet, and the last sub-channel is connected to the sample outlet.

[0013] In some embodiments of the present application, a fluid acceleration structure is provided in the sub-flow channel for accelerating the flow of the sample.

[0014] In some embodiments of the present application, an antibody layer is provided on the inner wall of the groove and / or the surface of the nanowire, and the antibody layer has the property of binding to the antigen in the cell to be captured.

[0015] It can be seen from this that the embodiments of the present application are mainly to effectively capture larger CTC cells by matching the groove size design with the CTC size to be captured, reducing the retention of non-target cells (such as white blood cells), thereby ensuring that the captured CTC has higher specificity, reducing the risk of false positives and helping to improve capture efficiency. The spaced arrangement of nanowires 111 increases the surface area inside the chip, provides more adsorption points for CTC, and further improves the capture rate. In detail, the multi-level design of the intervals between the nanowires 111 and the grooves effectively improves the capture ability of the chip. The nanowires 111 separate the grooves into multiple sub-grooves, which enhances the contact probability of cells with the chip surface during liquid flow, so that the CTC in the liquid sample can fully contact the nanowires 111, increasing the possibility of capture. Due to the precise matching of the groove size, the chip can effectively filter out smaller non-target cells, such as white blood cells and other blood components, making it difficult for most non-target cells to be retained in the grooves, thereby reducing the occurrence of nonspecific adsorption and improving the accuracy of the test results. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following is a brief introduction to the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0017] Figure 1 A schematic structural diagram of a microfluidic chip provided in an embodiment of the present utility model;

[0018] Figure 2 A schematic structural diagram of a substrate in a microfluidic chip provided in an embodiment of the present utility model;

[0019] Figure 3 A schematic structural diagram of another substrate in a microfluidic chip provided in an embodiment of the present utility model;

[0020] Figure 4 This is a schematic structural diagram of a substrate in a microfluidic chip provided by an embodiment of the present utility model.

[0021] Description of reference numerals:

[0022] 1. Substrate; 11. Groove; 111. Nanowire; 112. Sidewall; 113. Bottom wall; 2. Matrix; 21. Sample inlet; 22. Sample outlet; 23. Flow channel; 231. Sub-flow channel; 2311. Guide protrusion; 232. Connecting flow channel; 3. Encapsulation layer. DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making any creative efforts shall fall within the scope of protection of this application.

[0024] In the description of this application, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or the number of the technical features indicated. Therefore, a feature specified as "first" or "second" may explicitly or implicitly include one or more features. In the description of this application, "plurality" means two or more, unless otherwise specifically specified.

[0025] See Figures 1 to 4 The embodiment of the present application provides a microfluidic chip, comprising a substrate 1 and a substrate 2, wherein the substrate 2 is disposed on the substrate 1; a flow channel 23 is formed on a side of the substrate 2 facing the substrate 1; a plurality of grooves 11 are formed on a side of the substrate 1 facing the substrate 2, wherein the grooves 11 are connected to the flow channel 23;

[0026] A plurality of nanowires 111 are provided in the groove 11 , and the plurality of nanowires 111 are arranged at intervals to separate the bottom of the groove 11 into a plurality of sub-grooves 11 , and the size of the groove 11 matches the size of the cells to be captured.

[0027] Each nanowire 111 increases the surface area of ​​the groove 11 by its vertical arrangement, thereby providing more attachment points for the cells to be captured. The size of the groove 11 matches the size of the cells to be captured (e.g., CTC), so that larger target cells can be effectively captured, while smaller non-target cells (e.g., white blood cells) can pass smoothly and will not be adsorbed by the nanowires 111 or the antibodies in the groove 11. When the microfluidic chip is running, the sample liquid (e.g., blood) is injected into the flow channel 23 through the sample inlet on the substrate 2 and flows along the flow channel 23. The fluid enters the groove 11, and the CTC cells are trapped in the groove 11, and the contact area achieved by utilizing the nanowires 111 is increased, thereby achieving better and more efficient cell capture. Since the design of the groove 11 matches the size of the CTC, non-target cells are not easy to contact or bind to the nanowires 111, further reducing the possibility of nonspecific adsorption.

[0028] The technical solution provided in this application is mainly to effectively capture larger CTC cells by matching the size of the groove 11 with the size of the CTC to be captured, reducing the retention of non-target cells (such as white blood cells), thereby ensuring that the captured CTC has higher specificity, reducing the risk of false positives and helping to improve capture efficiency. The spaced arrangement of the nanowires 111 increases the surface area inside the chip, provides more adsorption points for CTC, and further improves the capture rate. In detail, the spacing between the nanowires 111 and the multi-level design of the groove 11 effectively improve the capture ability of the chip. The nanowires 111 separate the groove 11 into multiple sub-grooves 11, enhancing the contact probability of cells with the chip surface during liquid flow, so that the CTC in the liquid sample can fully contact the nanowires 111, increasing the possibility of capture. Due to the precise matching of the groove 11 size, the chip can effectively filter out smaller non-target cells, such as white blood cells and other blood components, making it difficult for most non-target cells to be retained in the groove 11, thereby reducing the occurrence of nonspecific adsorption and improving the accuracy of the test results.

[0029] In some embodiments, an encapsulation layer 3 is disposed on the side of the substrate 2 facing away from the base 1 to protect the nanowires 111 and grooves 11 within the substrate from external environmental influences (e.g., contamination, damage, etc.). The encapsulation layer 3 is transparent, protecting the nanostructures and microfluidic channels of the chip and ensuring that they are not disturbed by external factors during operation. Common materials for the encapsulation layer 3 include glass or transparent polymers (e.g., PDMS, PMMA, etc.).

[0030] In some embodiments, the inner wall of the groove 11 is hemispherical, and the groove 11 is connected to the plane of the base 1 in an arc shape, which helps to ensure that the shape of the groove 11 can better guide the cells into the capture area, avoid fluid blockage caused by right-angle or sharp-angle structures, and enhance cell fluidity and capture efficiency.

[0031] Furthermore, the maximum diameter of groove 11 ranges from 10 to 20 μm, and the maximum depth ranges from 5 to 15 μm. This size range matches the physical size characteristics of CTCs, ensuring effective capture of CTCs through physical screening in groove 11. Through precise size control, groove 11 can accommodate CTCs of varying sizes, thereby enhancing capture selectivity.

[0032] In this embodiment, a plurality of hemispherical grooves 11 are etched on the substrate 1 of the microfluidic chip. The inner wall of the groove 11 is hemispherical in design and is connected to the surface of the substrate 1 through an arc structure. This design can reduce the turbulent resistance of the fluid and help cells flow into the groove 11 area more smoothly. At the same time, the hemispherical groove 11 avoids the sharp-angle structure, reduces the shear force on the cells during the flow process, and ensures the activity and integrity of the cells. In addition, the diameter of the groove 11 is between 10um and 20um, and the depth is controlled at 5um to 15um. Such a design ensures the specificity of capture. The typical size of CTC is between 10um and 20um. The size of the groove 11 is set to match the size of the CTC, allowing larger CTC cells to enter the groove 11, while smaller non-target cells can pass through smoothly and are not easily retained or captured.

[0033] The technical solution provided in this embodiment reduces resistance to fluid flow by utilizing the hemispherical design of groove 11 and its arc-shaped connection to the plane of substrate 1, allowing the liquid sample to enter groove 11 more smoothly when flowing through the microfluidic channel. At the same time, the hemispherical inner wall avoids fluid turbulence caused by right-angled edges, guiding more CTCs into the groove 11 area, thereby improving the efficiency and success rate of cell capture. The hemispherical design of groove 11 reduces the shear force on cells during flow, prevents excessive mechanical stress from damaging the cells, and ensures the integrity of the captured CTC cell structure. This design not only improves the survival rate of cells after capture, but also provides higher quality samples for subsequent cell analysis (such as gene sequencing or immunoassays). The dimensions of groove 11 (10um to 20um diameter, 5um to 15um depth) precisely match the physical dimensions of CTCs, ensuring that CTCs can be effectively captured while preventing smaller non-target cells (such as white blood cells or red blood cells) from being accidentally captured. Through the physical size screening mechanism, this design significantly reduces the incidence of false positives and improves the specificity and accuracy of detection.

[0034] The groove 11 structure can be fabricated using micromachining techniques, such as photolithography and etching. First, photoresist is deposited on the surface of substrate 1. A hemispherical pattern is then formed using photolithography. Next, plasma or chemical etching is used to etch the groove 11 to the desired dimensions. The curved connection of groove 11 can be achieved by adjusting etching time and parameters, ensuring a smooth transition between the inner wall of groove 11 and substrate 1 without sharp angles.

[0035] In some embodiments, the inner wall of the groove 11 includes a plurality of side walls 112 and a bottom wall 113, and the plurality of side walls 112 are sequentially arranged and connected along the circumferential direction of the groove 11. The groove 11 can provide a larger contact surface area during fluid flow, and the angle design of the side walls 112 effectively improves the capture efficiency of CTCs. In detail, the inner wall of the groove 11 is composed of a plurality of side walls 112 and a bottom wall 113, each side wall 112 is connected to the bottom wall 113, and arranged along the circumferential direction of the groove 11. The design of the side walls 112 is not vertical, but forms a certain arc connection with the bottom wall 113, ensuring that the cells can slide smoothly into the groove 11 during the flow process without obstruction or shear force due to sharp angles, thereby reducing turbulence in the fluid, ensuring smooth flow of the fluid and increasing the probability of cell capture.

[0036] On this basis, the design of the multiple side walls 112 is further optimized, and they are inclined along the bottom wall 113 toward the opening of the groove 11, and gradually expand outward toward a position away from the center of the groove 11, so that the entire groove 11 is open. This open-shaped design can provide a larger and more obvious capture entrance for CTCs in flow, while also ensuring that the opening of the groove 11 is large enough for cells to enter the interior of the groove 11 during the flow. The inclined design of the side walls 112 of the groove 11 makes it difficult for non-target cells (such as smaller cells such as white blood cells) to be retained in the groove 11. Because the shape of the groove 11 is more suitable for cells of the size of CTCs, smaller non-target cells tend to continue to flow along the flow channel 23 and will not be retained on the inclined side walls 112 or the bottom, reducing non-specific adsorption and thus reducing the incidence of false positives during the detection process.

[0037] The groove 11 structure in this embodiment can be achieved using common micromachining techniques, such as photolithography and chemical etching. First, photolithography is used to deposit photoresist on the surface of substrate 1 to form a pattern in the shape of groove 11. Then, a chemical etching process is used to produce bottom wall 113 and sidewalls 112. The etching angle is controlled to achieve a smooth arc-shaped connection between bottom wall 113 and sidewalls 112 of groove 11. Finally, by adjusting the etching time and process parameters, the sidewalls 112 are arranged in sequence along the circumference of bottom wall 113 and form an outward-sloping structure.

[0038] Furthermore, the connection between the side wall 112 and the bottom wall 113 and the connection between the side walls 112 and the side walls 112 can be an arc connection, which is beneficial to improving the fit of the CTC cells in the groove 11 and avoiding the risk of small-sized cells or other impurities (all solid objects other than cells) being retained in the corners at the connection between the side walls 112 and the bottom wall 113 and the side walls 112 and the side walls 112.

[0039] In some embodiments, the grooves 11 are arranged in an array, the nanowires 111 are vertically arranged on the inner wall of the grooves 11, and the flow channel 23 is designed into multiple sub-channels 231 and connecting channels 232 to ensure that the flow path of the liquid sample in the chip is stable and uniform, thereby enhancing the CTC capture efficiency.

[0040] A plurality of grooves 11 are arranged in an array to ensure that in the microfluidic chip, each channel through which the liquid flows is aligned and connected to the corresponding groove 11. The grooves 11 are in a matrix or other form of array structure, so that the sample flow can cover a larger capture area, effectively increasing the total area of ​​the capture area, and ensuring that more CTC cells can enter the grooves 11 and be captured. In detail, by arranging a plurality of grooves 11 in an array, the effective capture area of ​​the microfluidic chip is greatly increased. The array structure ensures that the liquid sample can contact more grooves 11 when flowing through the microfluidic channel, increasing the probability of CTC being captured. At the same time, the array design ensures the uniformity of the capture area, avoids the sample only partially flowing through certain grooves 11, and improves the overall capture efficiency.

[0041] Multiple nanowires 111 are arranged vertically along the inner wall of groove 11. To increase the surface area of ​​groove 11, nanowires 111 are arranged in a stepped pattern, with the highest nanowires 111 extending gradually from the bottom of groove 11, forming a multi-level capture surface. The highest point of these nanowires 111 does not exceed the height of the substrate 1 plane, ensuring that the fluid in flow channel 23 can flow smoothly through the nanowires 111 within the overall chip structure and does not interfere with the normal flow of the fluid. Specifically, the stepped arrangement of nanowires 111 provides a larger surface area, significantly improving the capture efficiency within each groove 11. Nanowires 111 are arranged vertically along the inner wall of groove 11, and their height gradually increases from the bottom of groove 11 through a stepped structure, forming a multi-layer capture area. Because CTCs come into contact with the surfaces of multiple nanowires 111 during flow, the capture efficiency is significantly improved. This design is particularly suitable for capturing more CTCs and reducing interference from non-target cells.

[0042] Furthermore, the flow channel 23 includes a plurality of sub-flow channels 231 and a connecting flow channel 232. The sample enters the first sub-flow channel 231 from the sample inlet 21, and then flows to the subsequent sub-flow channels 231 in sequence through the connecting flow channel 232, and finally flows out from the sample outlet 22. The plurality of sub-flow channels 231 are arranged in an array, and the adjacent sub-flow channels 231 are connected by the connecting flow channel 232 to ensure that the sample can be evenly distributed to each sub-flow channel 231 when flowing through the chip, and flows into the corresponding capture groove 11 through each sub-flow channel 231, thereby ensuring the uniformity and stability of the capture. In detail, the sample enters the first sub-flow channel 231 from the sample inlet 21, and flows into the other sub-flow channels 231 in sequence through the connecting flow channel 232. This multi-segment flow channel 23 design ensures that the sample can gradually cover the area of ​​each groove 11, thereby making the capture process more uniform. At the same time, the multi-segment flow channel 23 ensures a balanced distribution of fluid pressure through the connection of the connecting flow channel 232, avoiding excessively fast or slow sample flow rates in certain grooves 11. The multi-segment design of the flow channel 23 system helps to evenly distribute the liquid sample, ensuring a stable fluid flow rate in each sub-flow channel 231, and avoiding fluctuations in capture efficiency due to uneven sample flow rates. In addition, the fluid exchange between the connecting flow channel 232 and the sub-flow channel 231 helps maintain the fluid balance of the entire system, reducing turbulence or local eddies generated by the fluid within the chip, thereby improving the stability and anti-interference ability of the CTC capture process.

[0043] In certain embodiments, a fluid acceleration structure is provided in the sub-flow channel 231 for accelerating the flow of the sample. For the fluid acceleration structure, a plurality of guide protrusions 2311 are included, and a plurality of guide protrusions 2311 are arranged in sequence along the length direction of the sub-flow channel 231, and a plurality of guide protrusions 2311 are arranged at intervals along the circumferential direction of the sub-flow channel 231, so that the adjacent guide protrusions 2311 are connected in sequence along the direction of the sample flow to form a spiral line. Along the direction of the sample flow, one end of the inner wall of the back ion flow channel 231 of the guide protrusion 2311 gradually approaches the axis of the sub-flow channel 231, so that a plurality of guide protrusions 2311 can define a plurality of turbulent regions, so that the non-CTC cells that do not match the size of the groove 11 are promoted, such as white blood cells that can flow through the groove 11 with the sample blood and will not be collected by the groove 11, thereby ensuring that the chip will not have a false positive capture result as much as possible. It should be noted that for the fluid acceleration structure, it may not adopt the above-mentioned structure, but may adopt other structures that can form turbulent flow. A simple example is given below:

[0044] The first method involves designing a contraction-expansion section within the subchannel 231. This involves reducing the width or height of certain sections of the subchannel 231, forcing the fluid flow rate to increase in that section. The contraction squeezes the fluid and accelerates its flow. As the fluid passes through the expansion section, the flow rate slows but the turbulence increases, thereby promoting contact between CTCs in the sample and the chip capture areas (e.g., grooves 11 and nanowires 111). This geometric change can increase flow rate and capture efficiency without changing the overall fluid pressure.

[0045] The second method involves arranging an array of micropillars within the subchannel 231. The spacing and height of these micropillars can be adjusted to create a localized fluid disturbance zone. This arrangement of micropillars alters the flow direction of the fluid, generating turbulence or vortices between the micropillars. This disturbs CTCs as they flow through these zones, increasing their chances of contact with the capture zone. The diameter of the micropillars typically ranges from a few microns to over ten microns, and the spacing between them is proportional to the width of the channel 23, creating a stable acceleration effect.

[0046] A third approach involves designing microfluidic nozzles in certain sections of sub-channel 231. These nozzles reduce the cross-sectional area of ​​the fluid channel, allowing the fluid to be ejected at a higher velocity. This nozzle structure rapidly increases the liquid flow rate in specific areas. Furthermore, the liquid passing through the nozzles generates small, localized turbulence in the groove 11 area, increasing contact between the CTC and the nanowires 111 within the groove 11.

[0047] In some embodiments, the inner walls of the grooves 11 of the microfluidic chip and / or the surfaces of the nanowires 111 are provided with an antibody layer that specifically binds to antigens in the cells to be captured. This antibody layer can specifically capture the cells to be captured through a specific antigen-antibody reaction. In this embodiment, the cells to be captured are circulating tumor cells, thereby improving the accuracy and specificity of capture.

[0048] Based on the expression of specific antigens on the CTC surface, antibodies that bind to CTC surface antigens, such as EpCAM antibodies or EGFR antibodies, are selected. These antibodies can bind to the corresponding antigens on the CTC surface, thereby achieving specific capture.

[0049] The antibody is modified to the inner wall of the groove 11 and the surface of the nanowire 111 by chemical bonding. The common biotin-streptavidin system or silanization technology can be used to modify the antibody. For example:

[0050] Biotin-streptavidin method: The inner wall of the groove 11 and the surface of the nanowire 111 are first modified with biotin, and then the biotin-labeled antibody is fixed to the groove 11 and the surface of the nanowire 111 through the streptavidin-biotin binding system.

[0051] Silanization technology: 3-aminopropyltriethoxysilane (APTES) is used to modify the amino functional groups on the surface of the grooves 11 and nanowires 111 of the silicon-based material, and then a cross-linking agent is used to fix the antibody on the surface to form a stable antibody layer.

[0052] The antibody layer is evenly coated on the inner walls of grooves 11 and the surfaces of nanowires 111. The inner walls of grooves 11 provide a large capture area, ensuring that CTCs can fully contact the antibody layer as fluid passes through. The high surface area of ​​nanowires 111 further increases the probability of antibody contact with CTCs, thereby enhancing capture specificity.

[0053] By modifying the antibody layer on the inner wall of the groove 11 and the surface of the nanowire 111, the chip can achieve specific capture of CTCs. The antibody layer can bind to antigens specifically expressed on the surface of CTCs (such as EpCAM, EGFR, etc.), ensuring that the captured cells have high specificity, reducing the retention and interference of non-target cells (such as white blood cells), and thus reducing the occurrence of false positive results. The antibody modification layer on the inner wall of the groove 11 and the surface of the nanowire 111 greatly increases the effective capture area of ​​the chip. When the liquid sample flows through the groove 11, the CTC can fully contact the antibody layer, increasing the capture probability. In addition, the high specific surface area design of the nanowire 111 further increases the chance of contact with the CTC, thereby improving the capture efficiency. By using chemical bonding methods (such as biotin-streptavidin system or silanization technology), antibodies can be firmly fixed to the groove 11 and the surface of the nanowire 111 to form a stable antibody layer. This stability ensures that the antibody layer will not easily fall off or lose activity during the sample flow and capture process, thereby maintaining long-term capture efficiency and being suitable for repeated use. The modification of the antibody layer enables the chip to achieve high-sensitivity capture of CTCs, especially when the sample size is small. The high specific binding of the antibody enables the effective capture of target cells even at lower CTC concentrations, significantly improving the detection sensitivity of the chip in clinical applications. By selecting different antibodies (such as antibodies against CTC-specific antigens of different cancer types), the chip can be expanded to CTC detection of multiple cancer types. After replacing the antibody layer, the chip can detect different types of circulating tumor cells and meet the needs of a wide range of clinical applications.

[0054] The basic concepts have been described above. It will be apparent to those skilled in the art that the detailed disclosure above is merely illustrative and does not limit the present application. Although not explicitly stated herein, those skilled in the art may make various modifications, improvements, and amendments to the present application. Such modifications, improvements, and amendments are suggested in the present application and remain within the spirit and scope of the exemplary embodiments of the present application.

[0055] At the same time, this application uses specific terms to describe the embodiments of this application. For example, "one embodiment," "an embodiment," and / or "some embodiments" refer to a certain feature, structure, or characteristic related to at least one embodiment of this application. Therefore, it should be emphasized and noted that "one embodiment," "an embodiment," or "an alternative embodiment" mentioned twice or multiple times in different locations in this specification does not necessarily refer to the same embodiment. In addition, certain features, structures, or characteristics in one or more embodiments of this application may be appropriately combined.

[0056] Similarly, it should be noted that, in order to simplify the description of this application and thus facilitate understanding of one or more embodiments of the application, the foregoing description of the embodiments of this application sometimes combines multiple features into a single embodiment, figure, or description thereof. However, this disclosure method does not mean that the subject matter of this application requires more features than those recited in the claims. In fact, the features of an embodiment may be fewer than all the features of the individual embodiments disclosed above.

[0057] Each patent, patent application, patent application publication, and other materials, such as articles, books, specifications, publications, and documents, cited in this application is hereby incorporated by reference in its entirety, except for any application history that is inconsistent with or conflicts with this application, and any document (currently or subsequently appended to this application) that limits the broadest scope of the claims of this application. It should be noted that if the descriptions, definitions, and / or terminology used in the accompanying materials are inconsistent with or conflict with the content of this application, the descriptions, definitions, and / or terminology used in this application will control.

[0058] The above are merely preferred embodiments of the present application and are not intended to limit the present application. Those skilled in the art will readily appreciate that various modifications and variations are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A microfluidic chip, characterized in that: The invention comprises a base and a base body, wherein the base body is arranged on the base body; a flow channel is provided on a side of the base body facing the base body; a plurality of grooves are provided on a side of the base body facing the base body, wherein the grooves are connected to the flow channel; Wherein, a plurality of nanowires are provided in the groove, and the plurality of nanowires are arranged at intervals to separate the bottom of the groove into a plurality of sub-grooves, and the size of the groove matches the size of the cells to be captured.

2. The microfluidic chip according to claim 1, characterized in that The inner wall of the groove is hemispherical, and the groove is connected to the plane of the base in an arc shape.

3. The microfluidic chip according to claim 2, characterized in that The maximum diameter of the groove ranges from 10um to 20um, and the maximum depth of the groove ranges from 5um to 15um.

4. The microfluidic chip according to claim 1, characterized in that The inner wall of the groove includes multiple side walls and a bottom wall. The multiple side walls are connected to the bottom wall and are arranged and connected in sequence along the circumferential direction of the bottom wall. The end of the side wall facing away from the bottom wall is connected to the plane of the base in an arc shape.

5. The microfluidic chip according to claim 4, characterized in that Along the direction from the bottom wall toward the opening of the groove, the side wall is inclined toward a position away from the center of the groove, so that the groove is open.

6. The microfluidic chip according to any one of claims 1 to 5, characterized in that: The plurality of grooves are arranged in an array and each of the grooves is aligned and communicated with the flow channel.

7. The microfluidic chip according to any one of claims 1 to 5, characterized in that: The plurality of nanowires are vertically arranged along the inner wall of the groove, and the plurality of nanowires are arranged in a stepped manner, and the side of the nanowire at the highest height away from the bottom of the groove is not higher than the height of the plane of the substrate.

8. The microfluidic chip according to any one of claims 1 to 5, characterized in that: The base is provided with a sample inlet and a sample outlet, and the flow channel includes multiple sub-channels and connecting channels. The multiple sub-channels are arranged in an array, and two adjacent sub-channels are connected through the connecting channel. Along the direction of the array arrangement, the first sub-channel is connected to the sample inlet, and the last sub-channel is connected to the sample outlet.

9. The microfluidic chip according to claim 8, characterized in that A fluid acceleration structure is provided in the sub-flow channel for accelerating the flow of the sample.

10. The microfluidic chip according to any one of claims 1 to 5, characterized in that: An antibody layer is provided on the inner wall of the groove and / or the surface of the nanowire, and the antibody layer has the property of binding to the antigen in the cell to be captured.

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