Microfluidic chip for cell detection

Abstract

The cell detection micro-fluidic chip comprises a filtering structure and a washing structure, the filtering structure is provided with a filtering cavity and a filtering part, the filtering part is arranged in the filtering cavity, and the filtering part is provided with a plurality of filtering channels which are arranged at intervals in the first direction; the washing structure is provided with a washing channel communicated with the filtering cavity, and the flow direction of the washing channel and the flow direction of the filtering channel are arranged at an angle. By arranging the filtering structure, large-volume cell clusters can be filtered, and single cells can pass through the filtering channel, so that a subsequent channel is prevented from being blocked, and the influence of the cell clusters on the accuracy of a cell quantity detection result is reduced. Furthermore, a washing channel is arranged so that cleaning liquid can be conveniently conveyed to the filtering cavity, then the filtering part can be cleaned, large-volume cell clusters can be discharged, the filtering part can conveniently carry out next-time filtering, the filtering structure does not need to be disassembled and assembled, operation is easy and convenient, the detection efficiency can be improved, and then the requirement for real-time detection can be better met.

Description

Technical Field

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

[0002] At present, in many production environments, it is usually necessary to detect the number of cells to determine the quality of the finished product. When the number of cells is within the qualified range, the quality of the finished product meets the output specifications. When the number of cells exceeds the set qualified range, it indicates that the quality of the finished product does not meet the production requirements.

[0003] The following method is usually used to detect the number of cells: stain the cells with dyes, then use optical technology to detect the number of cells per unit time and per unit area, and judge the quality of the finished product by comparing the test results with the qualified interval. During the testing process, when the quality of the finished product decreases, it is often easy for cells to clump and adhere, thus forming large cell clusters and blocking the channels for cell movement; in addition, cell clusters will also occupy the space of normal single cells, affecting the accuracy of the counting results.

[0004] In the related art, a filtering structure is usually set up to filter out cell clusters to allow other cells to move smoothly and ensure the accuracy of cell counting. However, the filtering structure needs to be frequently disassembled or inconvenient to operate, which prolongs the detection interval and reduces the detection efficiency, making it difficult to meet the needs of real-time detection. Summary of the invention

[0005] Based on this, it is necessary to provide a cell detection microfluidic chip that is easy to clean and conducive to real-time detection in order to address the above technical problems.

[0006] The cell detection microfluidic chip includes a filtering structure and a flushing structure. The filtering structure is provided with a filtering cavity and a filtering part. The filtering part is arranged in the filtering cavity, and the filtering part is provided with a plurality of filtering channels arranged at intervals along a first direction; the flushing structure is provided with a flushing channel connected to the filtering cavity, and the flow direction of the flushing channel is arranged at an angle to the flow direction of the filtering channel.

[0007] It is understandable that by setting up a filtering structure, large-volume cell clusters can be filtered. Specifically, the filter part can block large-volume cell clusters and allow single cells to pass through the filter channel to avoid blocking subsequent channels and reduce the impact of cell clusters on the accuracy of cell quantity detection results. Furthermore, by setting up a flushing channel to facilitate the delivery of cleaning liquid to the filter cavity, the filter part can be cleaned to discharge large-volume cell clusters, which is convenient for the filter part to filter next time. It is easy to operate and does not require the filter structure to be disassembled, cleaned, and then replaced. It can better meet the needs of real-time detection and help improve detection efficiency.

[0008] In one embodiment, the filter channel has an axial direction, and the axial direction of the filter channel is set at an angle to the first direction; there are multiple filter parts, which are arranged at intervals along the axial direction of the filter channel, and a flushing channel is provided between any two adjacent filter parts, and along the axial direction of the filter channel, a flushing channel is provided between the filter part close to the inlet of the filter cavity and the inlet of the filter cavity, and each flushing channel corresponds to and connects to one of the flushing channels.

[0009] It is understandable that multiple filter parts are provided to enhance the filtering effect on large cell clusters. A flushing channel is provided between two adjacent filter parts to communicate with the flushing channel, which facilitates the flow of cleaning fluid from the flushing channel into the flushing channel, thereby achieving the cleaning effect on each filter part.

[0010] In one embodiment, along the first direction, the flushing channels are provided on both sides of the filter structure, each of the flushing channels is connected to a corresponding flushing flow channel, and the angle between the flushing flow channel and the flushing channel is β, 150°≤β≤180°.

[0011] It is understandable that flushing channels are provided on both sides of the filter structure to facilitate the input and output of the cleaning liquid so that the cleaning liquid does not remain in the filter cavity. By limiting the angle range between the flushing flow channel and the flushing channel, the kinetic energy loss of the cleaning liquid is reduced, thereby ensuring smooth flow of the cleaning liquid.

[0012] In one embodiment, the filter portion includes a plurality of stop posts spaced apart along the first direction, and the filter channel is formed between any two adjacent stop posts along the first direction.

[0013] It can be understood that the stopper column can block large-volume cell clusters and allow single cells to pass through the filtration channels, so the structure is simple.

[0014] In one embodiment, along the first direction, the dimension of the filtration channel is d, 30µm≤d≤120µm.

[0015] It can be understood that by limiting the size of the filtration channel, large cell clusters cannot pass through the filtration channel, thereby ensuring the filtration effect.

[0016] In one of the embodiments, along the axial direction of the filter channel, the stop posts in any two adjacent filter parts are arranged in a staggered manner along the first direction.

[0017] It is understandable that such a configuration is used to enhance the barrier effect on cell clusters, thereby improving the filtering effect.

[0018] In one of the embodiments, the surface of the stop post facing the filter chamber inlet is configured as a curved surface.

[0019] It can be understood that the setting of the curved surface is conducive to the flow of the detected fluid along the curved surface, has a guiding effect on the detected fluid, and reduces fluid retention.

[0020] In one embodiment, the maximum dimension of the stop post along the axial direction of the filter channel is smaller than the maximum dimension of the stop post along the first direction.

[0021] It is understandable that, with such an arrangement, the stop column has a larger stop surface along the first direction to ensure the stopping effect, while the stop column has a smaller axial dimension along the filter channel, which is beneficial to reducing the axial dimension of the filter part along the filter channel, thereby allowing a larger number of filter parts to be arranged in the filter cavity.

[0022] In one embodiment, the cell detection microfluidic chip also includes a separation structure, which is provided with a separation chamber and a separation part, wherein the separation chamber is located at the outlet of the filter chamber and is connected with the filter chamber; the separation part is arranged in the separation chamber, and the separation part has a plurality of separation columns arranged at intervals, and each of the separation columns is provided with a separation end at one end facing the outlet of the filter chamber, and the separation end is gradually arranged along the axial direction of the filtration channel from the separation column toward the outlet of the filter chamber.

[0023] It can be understood that the separation column can disperse small cell clusters into multiple single cells through the tapered separation end, which is conducive to improving the accuracy of detection, and there is no need to add biochemical reagents for cell dispersion, and there is no need to wait for the dispersion reaction time, which is conducive to meeting the needs of real-time detection.

[0024] In one embodiment, at least two separation parts are provided, and along the axial direction of the filter channel, at least two separation parts are arranged at intervals, and the separation columns in any two adjacent separation parts are arranged in an alternating manner along the first direction.

[0025] It can be understood that such a configuration increases the hindering effect on small-volume cell clusters, and promotes the dispersion and separation of more small-volume cell clusters into multiple cells.

[0026] In one embodiment, along the axial direction of the filter channel, the size of the filter chamber along the first direction increases from the inlet of the filter chamber toward the outlet of the filter chamber; and / or, along the axial direction of the filter channel, the size of the separation chamber along the first direction decreases from the inlet of the separation chamber toward the outlet of the separation chamber.

[0027] It is understandable that, in this arrangement, the detected fluid gradually disperses as the filter cavity space gradually increases during the flow, and the contact area of ​​the filter portion also increases, which is conducive to enhancing the filtering effect. At the same time, as the separation cavity space gradually becomes smaller, it is conducive to the fluid being better concentrated after filtration and separation, so that the detected fluid continues to flow.

[0028] In one embodiment, the cell detection microfluidic chip is further provided with a first delivery channel, a second delivery channel and a mixing channel, the inlet of the first delivery channel is connected to the outlet of the separation chamber, and the outlet of the first delivery channel is simultaneously connected to the outlet of the second delivery channel and the inlet of the mixing channel; wherein, the second delivery channel is used to deliver a dye, and at least one of the first delivery channel and the second delivery channel is provided with a non-return structure.

[0029] It is understandable that the detected fluid in the first delivery channel and the dye in the second delivery channel can be mixed in the mixing channel to form a mixed fluid, so that the cells are stained and easy to observe and count. Among them, the setting of the non-return structure is conducive to the unidirectional flow of the detected fluid or dye to avoid backflow.

[0030] In one embodiment, at least a portion of the mixing channel is configured as a reciprocating winding structure.

[0031] It can be understood that the provision of the coiled structure prolongs the fluid flow time, facilitates the full mixing of the detected fluid and the dye, and helps improve the accuracy of the detection.

[0032] In one of the embodiments, in the mixing channel, the coiled structure is provided with a plurality of protrusions arranged at intervals; the surface of the protrusion facing the fluid flow direction is the liquid-facing surface, and the liquid-facing surface forms an angle α with the fluid flow direction, 30°≤α≤60°.

[0033] It is understandable that the setting of the protrusion can disturb the mixed fluid, thereby making the detected fluid and the dye mixed more fully and evenly. The liquid-facing surface is set at an angle with the flow direction so that the liquid-facing surface is inclined relative to the mixed fluid to guide the bubbles in the mixed fluid to flow with the mixed fluid, reduce bubble retention, and thus reduce the influence of bubbles on the mixing effect.

[0034] In one embodiment, the mixing channel is provided with an observation zone and a buffer zone. Along the fluid flow direction, the buffer zone is located between the coiled structure and the observation zone. The cross-sectional height dimension of the fluid flowing in the buffer zone is H, 100µm≤H≤1200µm, and the cross-sectional height dimension of the fluid flowing in the observation zone is h, 10µm≤h≤400µm.

[0035] It is understandable that the setting of the buffer zone is conducive to buffering the mixed fluid after disturbance, and is conducive to the mixed fluid entering the observation area more smoothly, thereby improving the observation effect. At the same time, such a setting makes the flow cross-section of the observation area smaller, so as to limit the flow of the mixed fluid flowing through the observation area, and facilitate the observation and counting of cells in the mixed fluid. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the conventional technology, the drawings required for use in the embodiments or the conventional technology descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0037] Figure 1 A front view of the cell detection microfluidic chip provided in this application; Figure 2 for Figure 1 A partial enlarged view of the middle A; Figure 3 A three-dimensional image of the cell detection microfluidic chip provided in this application; Figure 4 A three-dimensional image of the coiled structure in the cell detection microfluidic chip provided in the present application; Figure 5 A three-dimensional diagram of the structure where the observation area is located in the cell detection microfluidic chip provided in this application.

[0038] Explanation of the accompanying drawings: 100, cell detection microfluidic chip; 10, filtering structure; 101, filtering cavity; 11, filtering part; 111, filtering channel; 112, flushing channel; 113, stopping column; 20, flushing structure; 21, flushing channel; 30, separation structure; 301, separation cavity; 31, separation part; 311, separation column; 3111, separation end; 40, first conveying channel; 50, second conveying channel; 60, mixing channel; 61, winding structure; 611, protrusion; 6111, liquid facing surface; 601, buffer zone; 602, observation area; 62, slope structure. DETAILED DESCRIPTION

[0039] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. Preferred embodiments of the present invention are provided in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0040] It should be noted that when an element is referred to as being "fixed to" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only.

[0041] In this document, spatially related terms such as "upper" and "lower" are defined with reference to the accompanying drawings. Therefore, it will be understood that "upper" and "lower" are used interchangeably. It will be understood that when a layer is referred to as being "on" another layer, it can be directly formed on the other layer, or intervening layers may also be present. Therefore, it will be understood that when a layer is referred to as being "directly on" another layer, there are no intervening layers interposed therebetween.

[0042] In the accompanying drawings, the sizes of layers and regions may be exaggerated for clarity. It is understood that when a layer or element is referred to as being "on" another layer or substrate, the layer or element may be directly on the other layer or substrate, or there may be intervening layers. In addition, it is also understood that when a layer is referred to as being "between" two layers, the layer may be the only layer between the two layers, or there may be one or more intervening layers. In addition, the same reference numerals always represent the same elements.

[0043] Hereinafter, although terms such as "first", "second", etc. may be used to describe various components, these components are not limited to the above terms. The above terms are only used to distinguish one component from another component. It will also be understood that expressions used in the singular form include plural expressions, unless the expression in the singular form has a significantly different meaning in the context. In addition, in the following embodiments, it will also be understood that the terms "including" and / or "having" used herein illustrate the presence of the stated features or components, but do not exclude the presence or addition of one or more other features or components.

[0044] In the following embodiments, when a layer, region, or element is "connected", it can be interpreted that the layer, region, or element is not only directly connected but also connected through other constituent elements placed therebetween. For example, when a layer, region, element, etc. is described as being connected or electrically connected, the layer, region, element, etc. can be connected or electrically connected not only directly or directly, but also through another layer, region, element, etc. placed therebetween.

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification are only for the purpose of describing specific embodiments and are not intended to limit the present application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0046] It should also be understood that the terms “include / comprises” or “having” and the like specify the presence of stated features, wholes, steps, operations, components, parts or combinations thereof, but do not exclude the possibility of the presence or addition of one or more other features, wholes, steps, operations, components, parts or combinations thereof.

[0047] See also Figures 1 to 5 The present application provides a cell detection microfluidic chip 100, which includes a filtering structure 10 and a flushing structure 20. The filtering structure 10 can filter large-volume cell clusters, and the flushing structure 20 can flush and discharge the filtered large-volume cell clusters, which is beneficial for the filtering structure 10 to perform filtering again later.

[0048] like Figure 1 As shown, further, the filter structure 10 is provided with a filter cavity 101 and a filter part 11, the filter part 11 is provided in the filter cavity 101, and the filter part 11 is provided with a plurality of filter channels 111 arranged at intervals along the first direction. In this way, the filter cavity 101 provides space for filtering the fluid, which is convenient for assembling the filter part 11, and the filter part 11 filters out large-volume cell clusters, so that the detected fluid can flow through the filter channel 111.

[0049] like Figure 1 As shown, further, the flushing structure 20 is provided with a flushing channel 21 connected to the filter cavity 101, and the flow direction of the flushing channel 21 is set at an angle to the flow direction of the filter channel 111. In this way, a cleaning liquid flows through the flushing channel 21, and the cleaning liquid flows from the flushing channel 21 into the filter cavity 101 to flush the filtered large-volume cell clusters out of the filter cavity 101, thereby cleaning the filter structure 10.

[0050] In summary, by providing the filter structure 10 and the flushing structure 20, the filter structure 10 can be flushed directly after the filtering is completed without taking out the filter structure 10 separately for cleaning, which is beneficial to saving time cost and better meeting the needs of real-time monitoring.

[0051] In actual operation, gas may be introduced into the cell detection microfluidic chip 100 to discharge residual moisture inside the cell detection microfluidic chip 100 .

[0052] For the sake of convenience of explanation, the first direction, the axial direction of the filter channel 111 and the height direction of the mixing channel 60 in the present application are arranged perpendicularly to each other, wherein the height directions of the first conveying channel 40, the second conveying channel 50, the filter channel 111 and the flushing channel 21 are consistent with the mixing channel 60. The following description will be made with the first direction as the x-axis direction, the axial direction of the filter channel 111 as the y-axis direction, and the height direction of the mixing channel 60 as the z-axis direction.

[0053] First, the filter structure 10 is described in detail.

[0054] like Figure 1 and Figure 2 As shown, in an optional embodiment, the filter channel 111 has an axial direction, and the axial direction of the filter channel 111 is set at an angle to the first direction; a plurality of filter parts 11 are provided, and are arranged at intervals along the axial direction of the filter channel 111. In this way, the detected fluid flows along the axial direction of the filter channel 111 to pass through the plurality of filter parts 11 to achieve multi-layer filtration, thereby enhancing the filtering effect on large-volume cell clusters.

[0055] like Figure 1 and Figure 2 As shown, further, a flushing channel 112 is provided between any two adjacent filter portions 11, and a flushing channel 112 is provided between the filter portion 11 near the inlet of the filter cavity 101 and the inlet of the filter cavity 101 along the axial direction of the filter channel 111, and each flushing channel 112 is connected to a corresponding flushing channel 21. In this arrangement, the cleaning liquid can enter the flushing channel 112 from the flushing channel 21, and the large volume of cell clusters retained in the filter portion 11 can be flushed out of the filter portion 11 and discharged from the space of the filter cavity 101.

[0056] like Figure 1 and Figure 2 As shown, in some embodiments, along the first direction, flushing channels 21 are provided on both sides of the filter structure 10, and each flushing channel 21 is connected to a flushing channel 112. In this way, the cleaning liquid enters from the flushing channel 21 on one side, passes through the filter structure 10, and flows out from the flushing channel 21 on the other side.

[0057] like Figure 2 As shown, in a specific embodiment, the angle between the flushing channel 112 and the flushing channel 21 is β, 150°≤β≤180°. In this way, the flushing channel 21 is smoothly arranged relative to the flushing channel 112, and the flushing channel 112 and the flushing channel 21 are not easy to form a clear corner, which reduces the obstruction of the flow of the cleaning liquid, so that the cleaning liquid has sufficient kinetic energy for flushing, and ensures the cleaning effect. Exemplarily, β=150°, 170° or 180°.

[0058] like Figure 1 and Figure 2As shown, in a specific embodiment, the filter part 11 includes a plurality of stopper posts 113 spaced apart along a first direction, and a filter channel 111 is formed between any two adjacent stopper posts 113 along the first direction. In this way, the column bodies of the stopper posts 113 block the large cell clusters, and the gaps between the stopper posts 113 serve as the filter channel 111 to facilitate fluid flow. The stopper posts 113 have a simple structure and are easy to produce and process.

[0059] like Figure 2 As shown, in a specific embodiment, along the first direction, the size of the filter channel 111 is d, 30µm≤d≤120µm. In this way, by defining the size of the filter channel 111 by a specific number, large cell clusters larger than the size can be stuck outside the filter channel 111, while other small cell clusters and single cells can pass through. In a specific embodiment, d=30µm, 80µm or 120µm.

[0060] like Figure 2 As shown, in some embodiments, along the axial direction of the filter channel 111, the stopper columns 113 in any two adjacent filter parts 11 are staggered along the first direction. In this way, the filter part 11 forms multiple obstacles, and the detected fluid can be filtered multiple times during the flow process to improve the filtering effect.

[0061] like Figure 2 As shown, in an optional embodiment, the surface of the stop column 113 facing the inlet side of the filter chamber 101 is set as a curved surface to guide the fluid to flow along the curved surface, reduce the retention of the fluid at the stop column 113, and improve the flow efficiency.

[0062] like Figure 1 and Figure 2 As shown, in a further embodiment, the maximum dimension of the stop post 113 along the axial direction of the filter channel 111 is smaller than the maximum dimension of the stop post 113 along the first direction, so as to ensure that the stop post 113 has a sufficient stop area along the first direction. Based on this, the cross section (i.e., the cross section) of the stop post 113 along the axial direction of the filter channel 111 can be set to an elliptical shape, that is, the stop post 113 is set to an elliptical cylinder. In other embodiments, the stop post 113 can also be set to a semi-elliptical cylinder, etc. In this way, the long axis distance of the elliptical cylinder or the semi-elliptical cylinder is consistent with the flushing direction of the cleaning liquid, so that the cleaning liquid can smoothly flush the cell clusters that are stopped, which is conducive to improving the cleaning efficiency.

[0063] In other embodiments, the cross-section of the stop post 113 may also be set to be circular, triangular, rectangular, etc., which are only used as examples.

[0064] like Figure 1 and Figure 2As shown, in some embodiments, along the axial direction of the filter channel 111, the size of the filter cavity 101 along the first direction increases from the inlet of the filter cavity 101 toward the outlet of the filter cavity 101. In this way, as the detected fluid flows, the space of the filter cavity 101 gradually increases, and the detected fluid gradually disperses in the filter cavity 101. The size of the filter part 11 along the first direction also increases as the space of the filter cavity 101 increases, thereby increasing the contact area with the detected fluid, slowing down the flow rate of the detected fluid, and being able to fully contact with the filter part 11, resulting in a better filtering effect, and the filter part 11 can be provided with more stopper columns 113 along the first direction to enhance the filtering effect on the detected fluid.

[0065] Next, the separation structure 30 will be described.

[0066] like Figures 1 to 3 As shown, in some embodiments, the cell detection microfluidic chip 100 further includes a separation structure 30, the separation structure 30 is provided with a separation chamber 301 and a separation part 31, the separation chamber 301 is located at the outlet of the filter chamber 101 and communicates with the filter chamber 101, and the separation part 31 is arranged in the separation chamber 301. In this way, the detected fluid enters the separation chamber 301 after being filtered by the filter chamber 101, and the separation part 31 acts on the remaining cell clusters again, so that the cell clusters are dispersed into multiple single cells, so as to improve the accuracy of the detection.

[0067] like Figure 2 As shown, in a further embodiment, the separation part 31 has a plurality of separation columns 311 arranged at intervals, and each separation column 311 is provided with a separation end 3111 at one end facing the outlet of the filter chamber 101, and the separation end 3111 is gradually arranged along the axial direction of the filter channel 111 from the separation column 311 toward the outlet of the filter chamber 101. In this way, the separation end 3111 is relatively sharp, so as to separate the cell clusters into a plurality of single cells.

[0068] like Figure 2 As shown, in some embodiments, at least two separation parts 31 are provided, and at least two separation parts 31 are provided at intervals along the axial direction of the filter channel 111, and the separation columns 311 in any two adjacent separation parts 31 are arranged alternately along the first direction. In this way, the separation structure 30 forms multiple obstacles, so that the cell clusters contact with the multi-layer separation parts 31 when moving along the flow direction, and can be gradually separated into multiple smaller cell clusters, until finally separated into multiple single cells. This arrangement makes the separation of cell clusters more refined, which is conducive to improving the separation efficiency.

[0069] like Figures 1 to 3As shown, in a further embodiment, along the axial direction of the filter channel 111, the size of the separation chamber 301 along the first direction decreases from the inlet of the separation chamber 301 toward the outlet of the separation chamber 301. In this way, along the axial direction of the filter channel 111, the space of the separation chamber 301 gradually decreases, and the detected fluid can gradually gather in the separation chamber 301 after being dispersed in the filter chamber 101. The flow rate of the detected fluid increases as the space of the separation chamber 301 decreases, which is conducive to the stable output of the fluid.

[0070] like Figure 1 and Figure 3 As shown, further, the cell detection microfluidic chip 100 is further provided with a first delivery channel 40, a second delivery channel 50 and a mixing channel 60. Next, the first delivery channel 40, the second delivery channel 50 and the mixing channel 60 are described.

[0071] like Figure 1 and Figure 3 As shown, in some embodiments, the inlet of the first delivery channel 40 is connected to the outlet of the separation chamber 301, and the outlet of the first delivery channel 40 is simultaneously connected to the outlet of the second delivery channel 50 and the inlet of the mixing channel 60, wherein the second delivery channel 50 is used to deliver the dye. In this way, the detected fluid can flow into the first delivery channel 40 after being filtered and dispersed, and then flow from the first delivery channel 40 to the mixing channel 60. At the same time, the dye can flow from the second delivery channel 50 to the mixing channel 60, and the dye is mixed with the detected fluid in the mixing channel 60 to dye the cells for easy observation.

[0072] like Figure 1 and Figure 3 As shown, in a specific embodiment, at least one of the first delivery channel 40 and the second delivery channel 50 is provided with a non-return structure, and the non-return structure is provided to prevent liquid from flowing back.

[0073] like Figure 1 and Figure 3 As shown, the check structure can be set as a Tesla valve structure, which is simple in design, not easy to be blocked, and has low maintenance cost. In other embodiments, a one-way valve can also be set to allow the fluid to flow in only one direction and not reverse flow.

[0074] like Figure 1 , Figure 3 and Figure 4 As shown, in a further embodiment, at least part of the mixing channel 60 is configured as a reciprocating winding structure 61. In this configuration, the detected fluid and the dye are mixed in the mixing channel 60 to form a mixed fluid, and flow along the winding direction of the winding structure 61, which can slow down the flow rate of the mixed fluid and promote the full mixing of the detected fluid and the dye. Exemplarily, the mixing channel 60 is configured as an "S"-shaped winding structure 61.

[0075] like Figure 4 As shown, in a specific embodiment, in the mixing channel 60, the coiled structure 61 is provided with a plurality of protrusions 611 arranged at intervals. In this way, the protrusions 611 have an obstructive effect on the mixed fluid, causing the mixed fluid to be disturbed and generate vortices, thereby promoting the mixing effect of the mixed fluid and making the mixing more uniform. When the mixed fluid passes through the protrusions 611, the space of the mixing channel 60 is reduced, the fluid is disturbed, and the flow rate becomes faster; when the mixed fluid passes through the gap between the protrusions 611 and the protrusions 611, the space of the mixing channel 60 is increased and the fluid flow rate is slowed down. With this arrangement, the flow rate of the mixed fluid changes continuously during the flow process, which is conducive to enhancing the mixing effect.

[0076] like Figure 4 As shown, in a further embodiment, the surface of the protrusion 611 facing the fluid flow direction is the liquid-facing surface 6111, and the liquid-facing surface 6111 forms an angle α with the fluid flow direction, 30°≤α≤60°. In this way, the liquid-facing surface 6111 is tilted to guide the bubbles in the mixed fluid to flow with the mixed fluid, avoid the bubbles from being stuck in the dead corner at the root of the protrusion 611, reduce the influence of the bubbles on the fluid mixing, and reduce the influence of the bubbles on the mixing effect of the mixed fluid. Exemplarily, α=30°, 45° or 60°.

[0077] like Figure 3 and Figure 5 As shown, in an optional embodiment, the mixing channel 60 is provided with an observation area 602 and a buffer area 601, and along the fluid flow direction, the buffer area 601 is located between the coiled structure 61 and the observation area 602. In this way, the mixed fluid is evenly mixed after being disturbed by the coiled structure 61, and continues to flow to the buffer area 601, so that the flow of the mixed fluid gradually stabilizes, which facilitates the mixed fluid to stably enter the observation area 602 for observation.

[0078] like Figure 3 and Figure 5 As shown, in a further embodiment, taking the cross section perpendicular to the fluid flow direction as the cross section, the cross section of the mixing channel 60 where the buffer zone 601 is located is larger than the cross section of the mixing channel 60 where the observation zone 602 is located, so as to control the fluid flow entering the observation zone 602, thereby facilitating counting cells in the observation zone 602.

[0079] like Figure 5As shown, the cross-sectional height dimension of the fluid flow in the buffer zone 601 is H, 100µm≤H≤1200µm, and the cross-sectional height dimension of the fluid flow in the observation zone 602 is h, 10µm≤h≤400µm. It should be noted that this is based on the fact that the cross-sectional width dimension remains unchanged, and only the cross-sectional height is changed. With this arrangement, the space of the buffer zone 601 is larger, which promotes the smooth movement of the mixed fluid, but the space of the buffer zone 601 is not too large to ensure that the mixed fluid has a sufficient flow rate. At the same time, the space of the observation zone 602 is smaller to control the fluid flow rate, but not too small to avoid the fluid flow rate being too fast to affect the observation effect.

[0080] Exemplarily, H=100µm, 1000µm or 1200µm; h=10µm, 300µm or 400µm.

[0081] like Figure 3 and Figure 5 As shown, in a further embodiment, the mixing channel 60 is constructed with slope structures 62 on both sides of the observation area 602, wherein one slope structure 62 is connected between the wall of the buffer zone 601 and the wall where the observation area 602 is located, so as to guide and transition the mixed fluid that will enter the observation area 602, and the other slope structure 62 is connected between the wall where the observation area 602 is located and the wall near the outlet of the mixing channel 60 to promote the discharge of the mixed fluid.

[0082] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0083] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A cell detection microfluidic chip, characterized in that: include: A filter structure (10) comprising a filter cavity (101) and a filter portion (11), wherein the filter portion (11) is arranged in the filter cavity (101), and the filter portion (11) is provided with a plurality of filter channels (111) arranged at intervals along a first direction; The flushing structure (20) is provided with a flushing channel (21) communicating with the filter chamber (101), and the flow direction of the flushing channel (21) is arranged at an angle to the flow direction of the filter channel (111).

2. The cell detection microfluidic chip according to claim 1, characterized in that: The filter channel (111) has an axial direction, and the axial direction of the filter channel (111) is arranged at an angle to the first direction; A plurality of filter portions (11) are provided and are spaced apart along the axial direction of the filter channel (111); a flushing channel (112) is provided between any two adjacent filter portions (11); and a flushing channel (112) is provided between the filter portion (11) close to the inlet of the filter cavity (101) and the inlet of the filter cavity (101) along the axial direction of the filter channel (111); each flushing channel (112) is connected to a corresponding flushing channel (21).

3. The cell detection microfluidic chip according to claim 2, characterized in that: Along the first direction, the scouring channels (21) are provided on both sides of the filter structure (10), each of the scouring channels (21) is connected to a corresponding scouring flow channel (112), and the included angle between the scouring flow channel (112) and the scouring channel (21) is β, 150°≤β≤180°.

4. The cell detection microfluidic chip according to claim 1, characterized in that: The filter portion (11) comprises a plurality of stop columns (113) arranged at intervals along the first direction, and the filter channel (111) is formed between any two adjacent stop columns (113) along the first direction.

5. The cell detection microfluidic chip according to claim 4, characterized in that: Along the first direction, the size of the filtering channel (111) is d, 30µm≤d≤120µm.

6. The cell detection microfluidic chip according to claim 4, characterized in that: Along the axial direction of the filter channel (111), the stop posts (113) in any two adjacent filter portions (11) are arranged in a staggered manner along the first direction.

7. The cell detection microfluidic chip according to claim 4, characterized in that: The surface of the stop column (113) facing the inlet side of the filter cavity (101) is configured as a curved surface.

8. The cell detection microfluidic chip according to claim 4, characterized in that: The maximum dimension of the stop column (113) along the axial direction of the filter channel (111) is smaller than the maximum dimension of the stop column (113) along the first direction.

9. The cell detection microfluidic chip according to claim 1, characterized in that: The cell detection microfluidic chip further comprises a separation structure (30), wherein the separation structure (30) is provided with a separation cavity (301) and a separation portion (31), wherein the separation cavity (301) is located at the outlet of the filtration cavity (101) and is in communication with the filtration cavity (101); The separation portion (31) is arranged in the separation chamber (301), and the separation portion (31) has a plurality of separation columns (311) arranged at intervals, and each of the separation columns (311) is provided with a separation end (3111) at one end facing the outlet of the filter chamber (101), and the separation end (3111) is arranged to gradually contract from the separation column (311) toward the outlet of the filter chamber (101) along the axial direction of the filter channel (111).

10. The cell detection microfluidic chip according to claim 9, characterized in that: At least two separation parts (31) are provided, and along the axial direction of the filter channel (111), at least two separation parts (31) are arranged at intervals, and the separation columns (311) in any two adjacent separation parts (31) are arranged in an interlaced manner along the first direction.

11. The cell detection microfluidic chip according to claim 9, characterized in that: Along the axial direction of the filter channel (111), the size of the filter cavity (101) along the first direction increases from the inlet of the filter cavity (101) toward the outlet of the filter cavity (101); and / or, Along the axial direction of the filter channel (111), the dimension of the separation chamber (301) along the first direction decreases from the inlet of the separation chamber (301) toward the outlet of the separation chamber (301).

12. The cell detection microfluidic chip according to claim 9, characterized in that: The cell detection microfluidic chip is further provided with a first delivery channel (40), a second delivery channel (50) and a mixing channel (60); the inlet of the first delivery channel (40) is connected to the outlet of the separation chamber (301); and the outlet of the first delivery channel (40) is simultaneously connected to the outlet of the second delivery channel (50) and the inlet of the mixing channel (60); The second delivery channel (50) is used to deliver the dye, and at least one of the first delivery channel (40) and the second delivery channel (50) is provided with a non-return structure.

13. The cell detection microfluidic chip according to claim 12, characterized in that: At least a portion of the mixing channel (60) is configured as a reciprocating winding structure (61).

14. The cell detection microfluidic chip according to claim 13, characterized in that: In the mixing channel (60), the coiled structure (61) is provided with a plurality of protrusions (611) arranged at intervals; The surface of the protrusion (611) facing the fluid flow direction is a liquid-facing surface (6111), and the liquid-facing surface (6111) forms an angle α with the fluid flow direction, 30°≤α≤60°.

15. The cell detection microfluidic chip according to claim 13, characterized in that: The mixing channel (60) is provided with an observation area (602) and a buffer area (601). Along the fluid flow direction, the buffer area (601) is located between the coiled structure (61) and the observation area (602). The cross-sectional height dimension of the fluid flowing in the buffer area (601) is H, 100µm≤H≤1200µm, and the cross-sectional height dimension of the fluid flowing in the observation area (602) is h, 10µm≤h≤400µm.

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