Microfluidic chip and microfluidic system

Abstract

The utility model discloses a micro-fluidic chip and a micro-fluidic system, the micro-fluidic chip comprises a first flow channel, a first buffer solution flow channel, a first waste liquid flow channel and a cleaning flow channel group, the first buffer solution flow channel, the first waste liquid flow channel and the cleaning flow channel group are communicated with the first flow channel, and the cleaning flow channel group comprises at least two cleaning flow channels which are sequentially arranged along the flow direction; the diameter of an inlet of the cleaning runner is smaller than that of a first target object; the micro-fluidic system further comprises micro valves arranged corresponding to the flow channels. When the first micro-valve and the first waste liquid micro-valve are in an open state to enable a single first target flow to flow to a first area, the first micro-valve and the first waste liquid micro-valve are switched to be in a closed state, and the first buffer liquid micro-valve and the cleaning micro-valve are in an open state to enable the single first target flow to flow to an inlet of one cleaning flow channel; and the liquid in the first area flows out through other cleaning flow channels. The single first target object can be screened out from the first carrying liquid containing the first target object A and the non-target object.

Description

TECHNICAL FIELD

[0001] The utility model relates to single cell sequencing technical field especially, it is a kind of microfluidic chip and microfluidic system. BACKGROUND

[0002] Circulating tumor cells (CTC) are a kind of rare cancer cells commonly found in the circulatory system of cancer patients, usually present in the blood or lymph of patients in vivo. Circulating tumor cells are shed from the primary tumor into the circulatory system, which can form secondary tumors as seeds. During this metastasis process, strong heterogeneity is observed in circulating tumor cells. Phenotypic variation between circulating tumor cell and molecular characteristics indicates the presence of specific circulating tumor cell subpopulations, and this variation can produce different metastatic potential. Analysis of CTCs of breast cancer patients at the single-cell level can reveal the internal heterogeneity of patient cancer-related gene expression, which can further reveal the molecular pathways activated or altered during tumor and metastasis evolution, enabling researchers to obtain important information about metastasis mechanisms and genomic changes, which will help drug resistance research, enhance cancer treatment and cancer management.

[0003] The number of circulating tumor cells in the sample is rare, and when facing the demand of single-cell sequencing of low sample amount, the single-cell sequencing system based on valve has the advantages of low cost and high RNA capture efficiency. The current commercial single-cell sequencing technology based on droplets or micropores has high single-cell capture efficiency and cell throughput, however, in addition to circulating tumor cells, there are also red blood cells, white blood cells and other cells in the sample, and the large amount of red blood cell and white blood cell contamination reduces the accuracy of single-cell gene sequencing and increases the cost of sequencing. UTILITY MODEL CONTENT

[0004] The utility model aims at at least one of the technical problems existing in prior art. To this end, the utility model provides a microfluidic chip, which can reduce the pollution of non-target objects to target objects.

[0005] The utility model further provides a microfluidic system.

[0006] According to the microfluidic chip in the first embodiment of the utility model, it is applied to the screening of the first target object, the microfluidic chip includes a first flow channel, a first buffer solution flow channel, a first waste liquid flow channel and a cleaning flow channel group connected to the first flow channel respectively, the first flow channel is used for flowing liquid containing the first target object, along the flow direction of the liquid in the first flow channel, the first waste liquid flow channel and the cleaning flow channel group are both arranged downstream of the first buffer solution flow channel, the cleaning flow channel group includes at least two cleaning flow channels arranged in sequence along the flow direction, the diameter of the inlet of the cleaning flow channel is less than the diameter of the first target object;

[0007] The microfluidic chip further comprises a first micro valve corresponding to the first flow channel, a first buffer micro valve corresponding to the first buffer flow channel, a first waste liquid micro valve corresponding to the first waste liquid flow channel, and a cleaning micro valve corresponding to each of the cleaning flow channels, the first micro valve being used to control the opening and closing of the first flow channel, the first buffer micro valve being used to control the opening and closing of the first buffer flow channel, the first waste liquid micro valve being used to control the opening and closing of the first waste liquid flow channel, and the cleaning micro valve being used to control the opening and closing of each of the cleaning flow channels.

[0008] The first flow channel between the first buffer flow channel and the cleaning flow channel group is defined as a first region, and the microfluidic chip is configured to: when the first micro valve and the first waste liquid micro valve are in an open state, after a single first target flows into the first region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer micro valve and the cleaning micro valve are in an open state, so that the single first target flows into the inlet of one of the cleaning flow channels and stops at the inlet, and the liquid in the first region flows out through the other cleaning flow channels.

[0009] The microfluidic chip according to the embodiments of the present application has at least the following beneficial effects:

[0010] The microfluidic chip of the present embodiment filters a single first target from the first carrier liquid containing the first target A and non-targets by setting corresponding flow channels and valves and switching the valves, reduces the pollution of non-targets, and thus can improve the accuracy of subsequent detection.

[0011] In other embodiments of the present application, the first waste liquid flow channel and the cleaning flow channel are independent flow channels, and the diameter of the first waste liquid flow channel is greater than the diameter of the cleaning flow channel.

[0012] In other embodiments of the present application, the first buffer flow channel, the first waste liquid flow channel, and the cleaning flow channel group are sequentially arranged along the flow direction.

[0013] The first flow channel between the first buffer flow channel and the first waste liquid flow channel is defined as a second region, and when the first micro valve and the first waste liquid micro valve are in an open state, and a single first target flows into the first region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer micro valve and the cleaning micro valve are in an open state, comprising: when the first micro valve and the first waste liquid micro valve are in an open state, and a single first target flows into the second region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer micro valve and the cleaning micro valve are switched to an open state.

[0014] In other embodiments of the utility model, at least one the cleaning flow channel is the first waste liquid flow channel, and the cleaning micro valve is the first waste liquid micro valve.

[0015] In other embodiments of the utility model, the cleaning flow channel comprises a first cleaning section in communication with the first flow channel, the first cleaning section has the inlet at one end thereof facing the first flow channel, and the cross-sectional area of the first cleaning section gradually increases from the one end having the inlet along the flow direction of the liquid in the cleaning flow channel.

[0016] In other embodiments of the utility model, along the flow direction of the liquid in the cleaning flow channel, the cleaning flow channel further comprises a second cleaning section in communication with the first cleaning section, and the cross-sectional area of the second cleaning section is greater than or equal to the maximum cross-sectional area of the first cleaning section.

[0017] In other embodiments of the utility model, the diameter of the inlet of the first waste liquid flow channel is 5 microns to 10 microns.

[0018] In other embodiments of the utility model, the microfluidic chip further comprises a connecting flow channel, one end of the connecting flow channel is in communication with the first flow channel, the other end of the connecting flow channel is in communication with each cleaning flow channel, and the length of the connecting flow channel is 3 microns to 8 microns along the flow direction of the liquid in the connecting flow channel.

[0019] In other embodiments of the utility model, the microfluidic chip further comprises a second flow channel, an oil liquid flow channel, a second buffer liquid flow channel and a pairing flow channel, the pairing flow channel is in communication with the oil liquid flow channel, the first flow channel, the second flow channel and the second buffer liquid flow channel are all in communication with the pairing flow channel, and the second flow channel is used for flowing the liquid containing a second target object.

[0020] The microfluidic chip further comprises a pairing micro valve arranged corresponding to the pairing flow channel, a second micro valve arranged corresponding to the second flow channel, an oil liquid micro valve arranged corresponding to the oil liquid flow channel and a second buffer liquid micro valve arranged corresponding to the second buffer liquid flow channel, the pairing micro valve is used for controlling the on-off of the pairing flow channel, the second micro valve is used for controlling the on-off of the second flow channel, the oil liquid micro valve is used for controlling the on-off of the oil liquid flow channel, and the second buffer liquid micro valve is used for controlling the on-off of the second buffer liquid flow channel.

[0021] When the single first target object and the single second target object exist in the pairing flow channel, the first micro valve, the second micro valve, the first buffer micro valve, the first waste liquid micro valve and the cleaning micro valve are in the closed state, and the pairing micro valve and the second buffer micro valve are in the open state, so that the single first target object and the single second target object in the pairing flow channel are sent into the oil liquid in the oil liquid flow channel to form droplets.

[0022] In other embodiments of the utility model, the microfluidic chip further includes a second waste liquid flow channel and a second waste liquid micro valve corresponding to the second waste liquid flow channel, the second waste liquid flow channel is communicated with the pairing flow channel, and the second waste liquid micro valve is used for controlling the on-off of the second waste liquid flow channel.

[0023] In other embodiments of the utility model, the microfluidic chip is further configured to: when the single first target object stops at the inlet of one of the cleaning flow channels, and the first buffer micro valve and the cleaning micro valve remain in the open state for a set time, the cleaning micro valve is switched to the closed state, and the second waste liquid micro valve is switched to the open state, so that the single first target object enters the pairing flow channel from the first flow channel.

[0024] In other embodiments of the utility model, the microfluidic chip further includes a second waste liquid flow channel and a second waste liquid micro valve corresponding to the second waste liquid flow channel, the second waste liquid flow channel is communicated with the pairing flow channel, and the second waste liquid micro valve is used for controlling the on-off of the second waste liquid flow channel.

[0025] When the first micro valve, the first waste liquid micro valve, the cleaning micro valve and the pairing micro valve are in the closed state, and the first buffer micro valve and the second waste liquid micro valve are in the open state, liquid in the first flow channel can flow out through the pairing flow channel and the second waste liquid flow channel.

[0026] And / or, when the pairing micro valve is in the closed state, and the second micro valve and the second waste liquid micro valve are in the open state, liquid in the second flow channel can flow out through the pairing flow channel and the second waste liquid flow channel.

[0027] In other embodiments of the present application, the microfluidic chip further comprises a second flow channel, an oil flow channel and a matching flow channel, the matching flow channel is communicated to the oil flow channel, and the first flow channel and the second flow channel are both communicated to the matching flow channel.

[0028] The microfluidic chip further comprises a matching micro valve arranged corresponding to the matching flow channel and a second micro valve arranged corresponding to the second flow channel, the matching micro valve is used for controlling the opening and closing of the matching flow channel, and the second micro valve is used for controlling the opening and closing of the second flow channel.

[0029] When the single first target object from the first flow channel and the single second target object from the second flow channel exist in the matching flow channel, the first micro valve, the second micro valve, the first waste liquid micro valve and the cleaning micro valve are all in the closed state, and the matching micro valve and the first buffer micro valve are in the open state, so that the buffer liquid in the first buffer micro valve sends the single first target object and the single second target object in the matching flow channel into the oil liquid in the oil flow channel to form a droplet.

[0030] In other embodiments of the present application, the second target object is a detection microsphere, and the detection microsphere comprises a marker core and a magnetic coating layer coated on the marker core; wherein the marker core comprises a polymer core and a detection marker on the surface of the polymer core; and the surface of the magnetic coating layer is combined with a primer chain.

[0031] In other embodiments of the present application, the surface of the magnetic coating layer is modified with streptavidin, the primer chain is modified with biotin, and the primer chain is combined with streptavidin on the surface of the magnetic coating layer through biotin.

[0032] In other embodiments of the present application, the number of primer chains combined on the surface of the magnetic coating layer is 5*107~2*108.

[0033] In other embodiments of the present application, the polymer comprises a copolymer or homopolymer formed by at least one monomer of styrene, acrylic acid, acrylic ester and methyl acrylic ester.

[0034] In other embodiments of the present application, the magnetic coating layer comprises at least one of ferroferric oxide, ferrous oxide and ferrite material.

[0035] In other embodiments of the present application, the detection marker comprises a fluorescent detection marker.

[0036] In other embodiments of the present application, the fluorescent detection marker comprises at least one of APC, coomassie brilliant blue and Nile blue chloride.

[0037] In other embodiments of the utility model, the diameter of the detection microsphere is 10-20 μm.

[0038] The aforementioned microfluidic chip is applied to single cell sequencing, cell screening, cell interaction detection, cell omics analysis, proteomics analysis, preparation of cell treatment products or cell drugs.

[0039] According to the microfluidic system of the second embodiment of the utility model, comprising:

[0040] The microfluidic chip;

[0041] The detection module;

[0042] The first flow channel has a first identification site, and the detection module is configured to identify the single first target object at the first identification site, wherein when the detection module identifies the single first target object, the first micro valve and the first waste liquid micro valve are switched to a closed state to enable the single first target object to be located in the first region.

[0043] In other embodiments of the utility model, when the detection module does not identify the single first target object, the first micro valve and the first waste liquid micro valve are kept in an open state, and the first buffer micro valve and the cleaning micro valve are kept in a closed state, so that the liquid in the first flow channel can flow out through the first waste liquid flow channel.

[0044] In other embodiments of the utility model, the detection module includes a camera and a controller, the controller is configured to control the camera to shoot a first image of the first identification site, and the controller is further configured to identify the single first target object based on the first image.

[0045] In other embodiments of the utility model, the detection module includes a first light source, a first light detection device and a controller, the controller is configured to control the first light source to emit first detection light to the first identification site, the first detection light can excite first fluorescence after irradiating the single first target object, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target object.

[0046] In other embodiments of the utility model, the detection module further includes a first light transmission device and a second light transmission device, the first light transmission device is configured to receive the first detection light of the first light source and conduct the first detection light to the first identification site, and the second light transmission device is configured to receive the first fluorescence and conduct the first fluorescence to the first light detection device.

[0047] In other embodiments of the utility model, the first flow channel includes first flow channel section and second flow channel section which are sequentially arranged along the flow direction, the first buffer solution flow channel, the first waste liquid flow channel and the cleaning flow channel group are all communicated to the second flow channel section, the axis of the first flow channel section and the second flow channel section is intersected, the first identification position is arranged in the second flow channel section, wherein the first light transmission device is arranged on the side of the first flow channel section away from the second flow channel section and points to the second flow channel section, the second light transmission device is arranged in the second flow channel section corresponding to the first identification position, the axis of the first light transmission device and the second light transmission device is intersected.

[0048] In other embodiments of the utility model, the axis of the first flow channel section and the second flow channel section is perpendicular, the axis of the first light transmission device and the second light transmission device is perpendicular, and the second light transmission device is arranged on the side of the second flow channel section away from the first flow channel section and points to the first flow channel section.

[0049] In other embodiments of the utility model, the first light transmission device and the second light transmission device are respectively arranged on the opposite sides of the first flow channel, and the first light transmission device and the second light transmission device are coaxially arranged.

[0050] In other embodiments of the utility model, the detection module includes a first detection electrode and a controller, the first detection electrode is arranged in the first identification position and extends into the first flow channel, and the controller is configured to identify the single first target based on the signal detected by the first detection electrode.

[0051] In other embodiments of the utility model, along the flow direction, the first identification position is located upstream of the first buffer solution flow channel.

[0052] The microfluidic system according to the third embodiment of the utility model comprises:

[0053] The microfluidic chip;

[0054] A detection module;

[0055] The first flow channel between the cleaning flow channel group and the matching flow channel has a second identification position, and the detection module is configured to identify the single first target at the second identification position, wherein when the detection module identifies the single first target, the first micro valve and the matching micro valve are both in a closed state to keep the single first target in the matching flow channel.

[0056] And / or, the second flow channel has a third identification position, and the detection module is configured to identify a single second target object at the third identification position, wherein when the detection module identifies the single second target object, the second micro valve and the paired micro valve are both switched to a closed state to keep the single second target object in the paired flow channel.

[0057] In other embodiments of the present application, the first flow channel has a first identification position, and the detection module is configured to identify the single first target object at the first identification position, wherein when the detection module identifies the single first target object, the first micro valve and the paired micro valve are both switched to a closed state to keep the single first target object in the first region.

[0058] The microfluidic system further comprises a carrier platform configured to carry the microfluidic chip and movable between a first position and a second position.

[0059] When the carrier platform is located at the first position, the detection module is configured to identify the single first target object at the first identification position; when the carrier platform is located at the second position, the detection module is configured to identify the single first target object at the second identification position, and / or the detection module is configured to identify the single second target object at the third identification position.

[0060] Additional aspects and advantages of the present application will be given in part in the following description, and will become apparent from the following description, or will be learned by practice of the present application. BRIEF DESCRIPTION OF DRAWINGS

[0061] The present application will be further described below in conjunction with the drawings and examples, wherein:

[0062] Figure 1 FIG. 1 is a schematic view of a microfluidic chip in a first embodiment of the present application;

[0063] Figure 2 FIG. 2 is an enlarged schematic view of a F region in FIG. 1; Figure 1

[0064] Figure 3 FIG. 3 is an enlarged schematic view of a paired flow channel in FIG. 2; Figure 2

[0065] FIG. 4 is a flowchart of a process of realizing pairing of a first target object and a second target object by a microfluidic system in the first embodiment of the present application; Figure 4

[0066] FIG. 5 is an exploded schematic view of a microfluidic chip in the first embodiment of the present application; Figure 5

[0067] ​​Figure 6 FIG. 1 is a schematic diagram of a microfluidic chip in another embodiment of the application;

[0068] Figure 7 FIG. 2 is a schematic diagram of a microfluidic system in a second embodiment of the application;

[0069] Figure 8 FIG. 3 is a schematic diagram of a micro valve of the microfluidic system in an embodiment of the application in an open state and a closed state.

[0070] Reference signs:

[0071] microfluidic chip 100, base layer 110, control layer 120, first micro valve 121, diaphragm 1211, second micro valve 122, first buffer micro valve 123, first waste liquid micro valve 124, cleaning micro valve 125, oil micro valve 126, second buffer micro valve 127, matching micro valve 128, second waste liquid micro valve 129, flow channel layer 130, first flow channel 131, first region 1311, second region 1312, first flow channel section 1313, second flow channel section 1314, second flow channel 132, first buffer flow channel 133, first waste liquid flow channel 134, cleaning flow channel 135, first cleaning section 1351, second cleaning section 1352, oil flow channel 136, second buffer flow channel 137, matching flow channel 138, second waste liquid flow channel 139, connecting flow channel 1310;

[0072] detection module 200, first light transmission device 210, second light transmission device 220;

[0073] first target object A;

[0074] second target object B;

[0075] first identification site C;

[0076] second identification site D;

[0077] third identification site E;

[0078] droplet G DETAILED DESCRIPTION

[0079] Embodiments of the application are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference signs represent the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by reference to the drawings are exemplary and are only used to explain the application and cannot be understood as a limitation of the application.

[0080] In the description of the utility model, if the meaning of several is more than one, the meaning of multiple is more than two, greater than, less than, more than and the like are understood as not including the number, above, below, within and the like are understood as including the number. If the first, second is described, it is only used for distinguishing technical features for the purpose, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or implicitly indicating the sequence of indicated technical features.

[0081] In the description of the utility model, if the meaning of several is more than one, the meaning of multiple is more than two, greater than, less than, more than and the like are understood as not including the number, above, below, within and the like are understood as including the number. If the first, second is described, it is only used for distinguishing technical features for the purpose, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or implicitly indicating the sequence of indicated technical features.

[0082] In the description of the utility model, unless otherwise explicitly limited, the words such as setting, installation, connection and the like should be understood broadly, and the person skilled in the art can determine the specific meaning of the above words in the utility model in combination with the specific content of the technical scheme.

[0083] In the description of the utility model, the description of reference terms "one embodiment", "some embodiments", "illustrative embodiment", "example", "specific example" or "some examples" means that the specific features, structures, materials or characteristics described in combination with the embodiment or example are included in at least one embodiment or example of the utility model. In the specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0084] The first embodiment of the utility model proposes a microfluidic system, referring to Figure 1 , Figure 2 The microfluidic system comprises a first flow channel 131, a first buffer flow channel 133, a first waste liquid flow channel 134 and a cleaning flow channel group respectively connected to the first flow channel 131, the cleaning flow channel group comprises at least two cleaning flow channels 135, the first flow channel 131 is used for flowing the first carrier liquid containing the first target object A, the first buffer flow channel 133 is used for flowing the buffer, and the cleaning flow channel 135 and the first waste liquid flow channel 134 are used for flowing the waste liquid. It should be noted that the waste liquid referred to herein is the first carrier liquid or the mixture of the first carrier liquid and the buffer without or substantially without the first target object A. It should be noted that in the embodiment, the first target object is a cell, such as a tumor cell.

[0085] In the flow direction of the liquid in the first flow channel 131, the first waste liquid flow channel 134 and the cleaning flow channel group are both arranged downstream of the first buffer liquid flow channel 133, that is, the first carrier liquid first reaches the first buffer liquid flow channel 133, and then reaches the first waste liquid flow channel 134 and the cleaning flow channel group, for example Figure 1 In the top-to-bottom direction, the first waste liquid flow channel 134 and the cleaning flow channel group are both arranged below the first buffer liquid flow channel 133. It should be noted that the order of the first waste liquid flow channel 134 and the cleaning flow channel group can not be limited in the utility model, and in Figure 1 In the embodiment shown, the cleaning flow channel group is located downstream of the first waste liquid flow channel 134, and in other embodiments, the first waste liquid flow channel 134 is located downstream of the cleaning flow channel group.

[0086] Referring to Figure 2 In the flow direction of the liquid in the first flow channel 131, the cleaning flow channel group includes at least two cleaning flow channels 135 arranged in sequence in the flow direction, and the diameter of the inlet of the cleaning flow channel 135 is smaller than the diameter of the first target object A. In this way, the first target object A will not be able to be discharged from the cleaning flow channel 135. In addition, when the first carrier fluid also contains non-target objects such as red blood cells, white blood cells and the like, the diameter of the inlet of the cleaning flow channel 135 is greater than the diameter of these non-target objects, so that the non-target objects will be able to be discharged from the cleaning flow channel 135. One of the cleaning flow channels 135 is used to intercept the first target object A, and the other cleaning flow channels 135 are used to pass the waste liquid through, and in Figure 2 In the embodiment shown, the cleaning flow channel 135 is provided as two, the right cleaning flow channel 135 is used to intercept the first target object A, and the left cleaning flow channel 135 is used to pass the waste liquid through. It should be noted that each cleaning flow channel 135 can be as shown in Figure 2 The front section (the part close to the first flow channel 131) is separated and the rear section (the part away from the first flow channel 131) is combined into one flow channel, in other words, Figure 2 It can be regarded as a block is arranged in the front section of a larger flow channel, which separates the front section of the larger flow channel into at least two independent channels, and in other embodiments, two completely independent cleaning flow channels 135 can also be directly arranged.

[0087] Referring to Figure 1The microfluidic system of the embodiment further comprises a plurality of microvalves, specifically, a first microvalve 121 corresponding to the first flow channel 131, a first buffer microvalve 123 corresponding to the first buffer flow channel 133, a first waste liquid microvalve 124 corresponding to the first waste liquid flow channel 134, and a cleaning microvalve 125 corresponding to each cleaning flow channel 135. The first microvalve 121 is used to control the opening and closing of the first flow channel 131, the first buffer microvalve 123 is used to control the opening and closing of the first buffer flow channel 133, the first waste liquid microvalve 124 is used to control the opening and closing of the first waste liquid flow channel 134, and the cleaning microvalve 125 is used to control the opening and closing of each cleaning flow channel 135. Taking the first flow channel 131 and the first microvalve 121 as an example, the first microvalve 121 controls the opening and closing of the first flow channel 131, which means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a free-flowing state, and the first carrier liquid can flow in the first flow channel 131. When the first microvalve 121 is in the closed state, the first flow channel 131 is in a cut-off state, and the first carrier liquid cannot flow in the first flow channel 131.

[0088] In some embodiments, with reference to Figure 8 The microvalve comprises a diaphragm. Taking the first microvalve 121 as an example, the diaphragm 1211 is arranged between the first flow channel 131 and the first microvalve control flow channel corresponding to the first flow channel 131. When the first microvalve 121 is in the open state, the diaphragm is in a horizontal state, and the first carrier liquid can flow in the first flow channel 131. When the diaphragm is driven to protrude towards the first flow channel 131 to be in the closed state, the diaphragm is close to the inner wall of the first flow channel 131 to cut off the first flow channel 131, and the first carrier liquid cannot flow in the first flow channel 131. For example, the inner wall of the first flow channel 131 is an arc-shaped inner wall, which facilitates the fitting of the diaphragm 1211 protruding towards the first flow channel 131, thereby ensuring the cutting-off effect. It should be noted that the driving force for protruding the diaphragm can be gas pressure. In the embodiment, the first microvalve control flow channel is filled with liquid, and an external gas source drives the liquid in the first microvalve control flow channel to flow, thereby pushing the diaphragm to protrude or reset. Compared with the direct driving mode by gas pressure, since the liquid is difficult to compress, this mode can realize the rapid response of the diaphragm, thereby adapting to high-speed pairing.

[0089] The embodiment can screen out a single first target object A from the first carrier liquid containing the first target object A and non-target objects. It mainly includes two steps. The first step is to screen out a single first target object A, and the second step is to separate the single first target object A from the non-target objects. Specifically, the first flow channel 131 between the first buffer flow channel 133 and the cleaning flow channel group is defined as the first region 1311 (for the convenience of understanding, the first flow channel 131 is divided into the first region 1311 and the second region 1312 in the following description). Figure 1The first micro valve 121 and the first waste liquid micro valve 124 are first switched to the open state, at this time, the first carrier liquid containing the first target object A and the non-target object will continuously flow from the first flow channel 131 to the first waste liquid flow channel 134, when it is detected (the specific detection scheme will be described later) that the single first target object A flows into the first region 1311 with the first carrier liquid, the first micro valve 121 and the first waste liquid micro valve 124 are switched to the closed state, at this time, the first carrier liquid A no longer flows, and the single first target object A will stay in the first region 1311, thereby completing the first step. Then, the first buffer liquid micro valve 123 and the cleaning micro valve 125 are switched to the open state, under the driving of the buffer liquid, the single first target object A staying in the first region will continue to flow to the cleaning flow channel group, and finally stop at the inlet of one of the cleaning flow channels 135 due to the larger diameter, at this time, the cleaning flow channel 135 is blocked by the first target object A, so that the buffer liquid and the residual first carrier liquid will continue to flow out of the other cleaning flow channels 135, thereby taking away the non-target object in the first region 1311, after the flushing of the buffer liquid, the first region 1311 only has or basically only has the first target object A, thereby completing the second step. It should be noted that the first buffer liquid micro valve 123 and the cleaning micro valve 125 can be in the closed state or in the open state during the completion of the first step.

[0090] As described above, the microfluidic chip 100 of the embodiment filters out the single first target object A from the first carrier liquid containing the first target object A and the non-target object by setting the corresponding flow channels and valves and switching the valves, reduces the pollution of the non-target object, and thus can improve the accuracy of subsequent detection.

[0091] On the basis of the first embodiment, in some embodiments of the utility model, with reference to Figure 1 , the first waste liquid flow channel 134 and the cleaning flow channel 135 are independent flow channels, and the diameter of the first waste liquid flow channel 134 is greater than that of the cleaning flow channel 135. Generally, the number of the first target object A in the first carrier liquid is small, so that the first waste liquid flow channel 134 with a larger diameter can realize rapid liquid discharge during the first step, thereby improving the screening speed of the microfluidic chip 100.

[0092] When the first waste liquid flow channel 134 and the cleaning flow channel 135 are independent flow channels, in some specific embodiments, with reference to Figure 1 , the first buffer liquid flow channel 133, the first waste liquid flow channel 134 and the cleaning flow channel group are sequentially arranged along the flow direction of the first carrier liquid, that is, when the first micro valve 121 is opened, the first carrier liquid will sequentially reach the first buffer liquid flow channel 133, the first waste liquid flow channel 134 and the cleaning flow channel group.

[0093] In the embodiment, the first flow channel 131 between the first buffer flow channel 133 and the first waste flow channel 134 is defined as a second region 1312, and the second region 1312 is part of the first region 1311. Based on the above structure, the aforementioned "after the single first target object A flows to the first region 1311, the first micro valve 121 and the first waste micro valve 124 are switched to the closed state, and the first buffer micro valve 123 and the cleaning micro valve 125 are in the open state" specifically refers to: the first buffer micro valve 123 and the cleaning micro valve 125 are in the closed state in the initial state, and after the single first target object A flows to the second region 1312, the first micro valve 121 and the first waste micro valve 124 are switched to the closed state, and the first buffer micro valve 123 and the cleaning micro valve 125 are switched to the open state, so that the single first target object A flows to the inlet of one of the cleaning flow channels 135.

[0094] Since the cleaning flow channel group is located downstream of the first waste flow channel 134, when the non-target object is flushed by the buffer solution, the entire first region 1311 can be flushed, thereby reducing the residual non-target objects as much as possible.

[0095] On the basis of the first embodiment, in some embodiments of the utility model, at least one cleaning flow channel 135 is the first waste flow channel 134, and the cleaning micro valve 125 is the first waste micro valve 124, in other words, the embodiment does not set a separate first waste flow channel 134, but uses at least one cleaning flow channel 135 in the cleaning flow channel group as the first waste flow channel 134, and correspondingly, the cleaning micro valve 125 thereon is also used as the first waste micro valve 124, so that the structure of the microfluidic chip 100 can be simplified.

[0096] On the basis of the first embodiment, in some embodiments of the utility model, referring to Figure 2 The cleaning flow channel 135 includes a first cleaning section 1351 in communication with the first flow channel 131, and it should be noted that the communication here includes direct communication with the first flow channel 131, and also includes indirect communication through, for example, subsequent connection flow channels 1310. The first cleaning section 1351 has an inlet at one end facing the first flow channel 131, wherein, along the flow direction of the liquid in the cleaning flow channel 135, for example Figure 2From the bottom to the top direction, the cross-sectional area of the first cleaning section 1351 gradually increases from one end with the inlet, that is, the cross-sectional area at the inlet of the first cleaning section 1351 is the smallest, so as to achieve the purpose of stopping the single first target object A, and at the same time, the gradually increasing cross-sectional area of the first cleaning section 1351 can improve the flux of the cleaning flow channel 135, thereby helping to improve the screening speed of the microfluidic chip 100. For example, when each cleaning flow channel 135 is an independent flow channel, the opposite two sides of the first cleaning section 1351 are provided as inclined surfaces or arc surfaces to achieve the purpose of gradually increasing the cross-sectional area, so that the flow resistance of the fluid can be reduced. When each cleaning flow channel 135 is as shown in Figure 2 , the first cleaning section 1351 is separated by a stop block and independent of each other, and the latter section is combined into an integrated flow channel, the first cleaning section 1351 can also be provided as an inclined surface or an arc surface on one side to achieve the purpose of gradually increasing the cross-sectional area.

[0097] When the cleaning flow channel 135 includes the first cleaning section 1351 communicating with the first flow channel 131, in some embodiments, referring to Figure 2 , along the flow direction of the liquid in the cleaning flow channel 135, the cleaning flow channel 135 further includes a second cleaning section 1352 communicating with the first cleaning section 1351, wherein when each cleaning flow channel 135 is an independent flow channel, the cross-sectional area of the second cleaning section 1352 can be equal to the maximum cross-sectional area of the first cleaning section 1351, and when each cleaning flow channel 135 is as shown in Figure 2 , the first cleaning section 1351 is separated by a stop block and independent of each other, and the latter section is combined into an integrated flow channel, the cross-sectional area of the second cleaning section 1352 can be greater than the maximum cross-sectional area of the first cleaning section 1351. By providing the second cleaning section 1352 with a larger cross-sectional area, the flux of the cleaning flow channel 135 can be improved, thereby helping to improve the screening speed of the microfluidic chip 100.

[0098] On the basis of the first embodiment, in some embodiments of the utility model, the diameter of the inlet of the first waste liquid flow channel 134 is 5-10 microns, so as to adapt to the stopping of common tumor cells. For example, the diameter of the inlet of the first waste liquid flow channel 134 is 5 microns, 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, etc.

[0099] On the basis of the first embodiment, in some embodiments of the utility model, referring to Figure 2 , the microfluidic chip 100 further includes a connecting flow channel 1310, one end of the connecting flow channel 1310 communicates with the first flow channel 131, and the other end communicates with each cleaning flow channel 135, that is, each cleaning flow channel 135 is indirectly connected to the first flow channel 131 through the connecting flow channel 1310. Along the flow direction of the liquid in the connecting flow channel 1310, for example Figure 2The length of the connecting flow channel 1310 is 3-8 microns in the up-down direction, so when a single first target object A stops at the entrance of a cleaning flow channel 135, the buffer solution cannot drive the first target object A to deviate from the stopping position due to the blocking effect of the connecting flow channel 1310. At the same time, by limiting the length of the connecting flow channel 1310 (which can also be understood as the depth of the recess of the connecting flow channel 1310), the subsequent buffer solution can drive the single first target object A to flow along the first flow channel 131 to the pairing flow channel 138 without being affected by excessive blocking.

[0100] On the basis of the first embodiment, in some embodiments of the utility model, referring to Figure 1 and Figure 3 , the microfluidic chip 100 further comprises a second flow channel 132, an oil flow channel 136, a second buffer solution flow channel 137 and a pairing flow channel 138. The second flow channel 132 is used for passing the second carrier liquid containing the second target object B, the second buffer solution flow channel 137 is used for passing the buffer solution, the oil flow channel 136 is used for passing the oil liquid that does not mix with the first carrier liquid, the second carrier liquid and the buffer solution, and the pairing flow channel 138 is used for stopping the single first target object A and the single second target object B. The pairing flow channel 138 is communicated to the oil flow channel 136, and the first flow channel 131, the second flow channel 132 and the second buffer solution flow channel 137 are all communicated to the pairing flow channel 138. In this embodiment, the first target object A is a cell, and the second target object B is a detection microsphere. Those skilled in the art can understand that the first target object A can be a cell, and the second target object B can also be a cell.

[0101] Correspondingly, the microfluidic chip 100 further comprises a pairing micro valve 128 arranged corresponding to the pairing flow channel 138, a second micro valve 122 arranged corresponding to the second flow channel 132 and a second buffer solution micro valve 127 arranged corresponding to the second buffer solution flow channel 137. The pairing micro valve 128 is used for controlling the opening and closing of the pairing flow channel 138, the second micro valve 122 is used for controlling the opening and closing of the second flow channel 132, and the second buffer solution micro valve 127 is used for controlling the opening and closing of the second buffer solution flow channel 137.

[0102] In this embodiment, referring to steps (c) and (d) in Figure 4 , when the single first target object A and the single second target object B exist in the pairing flow channel 138, the first micro valve 121 and the second micro valve 122 are in a closed state (the micro valve in Figure 4 is filled with black to represent the closed state), and the pairing micro valve 128 and the second buffer solution micro valve 127 are in an open state (the micro valve in Figure 4The single first target A and the single second target B in the pairing flow channel 138 are pushed by the buffer in the second buffer flow channel 137 into the oil in the oil flow channel 136 to form the droplet G.

[0103] As can be seen from the above, the present embodiment is provided with the pairing flow channel 138 for temporarily storing the single first target A and the single second target B, and the second buffer flow channel 137 for pushing the single first target A and the single second target B into the oil without pushing the single first target A and the single second target B by the first carrier liquid and the second carrier liquid, so that the first flow channel 131 and the second flow channel 132 can be kept in the closed state during the encapsulation, thereby completely avoiding other first targets and / or other second targets from entering the droplet G, which is beneficial to improve the success rate of the encapsulation and reduce the cell loss caused by multiple encapsulations.

[0104] When the microfluidic chip 100 further comprises the second flow channel 132, the oil flow channel 136, the second buffer flow channel 137 and the pairing flow channel 138 as described above, in some embodiments, referring to Figures 1 to 4 , the microfluidic system further comprises a second waste liquid flow channel 139 for discharging the first carrier liquid not containing or substantially not containing the first target A and the second carrier liquid not containing or substantially not containing the second target B, the second waste liquid flow channel 139 being in communication with the pairing flow channel 138. In addition, the microfluidic system further comprises a second waste liquid microvalve 129 arranged corresponding to the second waste liquid flow channel 139, the second waste liquid microvalve 129 being used for controlling the opening and closing of the second waste liquid flow channel 139.

[0105] On the basis of the above structure, when the single first target A stops at the inlet of one of the washing flow channels 135, and the buffer in the first buffer microvalve 123 has completed the non-target washing (refer to step (a) of Figure 4 ), the first microvalve 121, the first waste liquid microvalve 124, the washing microvalve 125, the second buffer microvalve 127 and the pairing microvalve 128 are all in the closed state, and the first buffer microvalve 123 and the second waste liquid microvalve 129 are in the open state, at this time, the buffer in the first buffer microvalve 123 will flow from the first flow channel 131 through the pairing flow channel 138 and into the second waste liquid flow channel 139, thereby driving the single first target A stopping at the inlet of the washing flow channel 135 to flow into the pairing flow channel 138 (refer to step (b) of Figure 4 ). When the single first target A is located in the pairing flow channel 138, the first buffer microvalve 123 is switched to the closed state, and then the single first target A will be stopped in the pairing flow channel 138.

[0106] When the microfluidic chip 100 further comprises the second waste liquid channel 139, in some embodiments, the microfluidic chip 100 is further configured to: when the single first target object A stops at the inlet of one of the washing channels 135, and the first buffer micro valve 123 and the washing micro valve 125 are kept in the open state for a set time, the washing micro valve 125 is switched to the closed state again, and the second waste liquid micro valve 129 is switched to the open state, so that the single first target object A enters the pairing channel 138 from the first channel 131. In this way, this embodiment can ensure that the buffer has sufficient washing time for the single first target object A, thereby reducing the residual of non-target objects. It should be noted that the aforementioned "set time" can be set and adjusted according to the data obtained during actual application, for example, by changing the length of time, detecting the residual rate of non-target objects after washing, and finally obtaining a washing time that meets the requirements.

[0107] When the microfluidic chip 100 further comprises the second channel 132, the oil liquid channel 136, the second buffer channel 137, and the pairing channel 138, in some embodiments, referring to Figures 1 to 4 , the microfluidic system further comprises a second waste liquid channel 139 and a second waste liquid micro valve 129 corresponding to the second waste liquid channel 139. The second waste liquid channel 139 and the second waste liquid micro valve 129 can be understood with reference to the foregoing embodiments.

[0108] When the first micro valve 121, the first waste liquid micro valve 124, the washing micro valve 125, and the pairing micro valve 128 are all in the closed state, and the first buffer micro valve 123 and the second waste liquid micro valve 129 are in the open state, the liquid in the first channel 131 can flow out through the pairing channel 138 and the second waste liquid channel 139, thereby enabling the flow of the single first target object A to the pairing channel 138.

[0109] In addition, when the pairing micro valve 128 is in the closed state, and the second micro valve 122 and the second waste liquid micro valve 129 are in the open state, the liquid in the second channel 132 can flow out through the pairing channel 138 and the second waste liquid channel 139, thereby enabling the flow of the single second target object B to the pairing channel 138.

[0110] In combination with the above, referring to Figure 1 and Figure 4 , a complete pairing process in an embodiment is described, which includes the following steps:

[0111] Screening of the first target A: initially, the first micro valve 121, the first buffer micro valve 123, the first waste liquid micro valve 124, the cleaning micro valve 125, the second buffer micro valve 127, the second waste liquid micro valve 129 and the pairing micro valve 128 are all in the closed state, then the first micro valve 121 and the first waste liquid micro valve 124 are opened, the first carrier liquid containing the first target A flows through the first flow channel 131 to the first waste liquid flow channel 134, when a single first target A appears in the first area 1311, the first micro valve 121 and the first waste liquid micro valve 124 are switched to the closed state, the first buffer micro valve 123 and the cleaning micro valve 125 are switched to the open state, the buffer liquid with the single first target A flows to the cleaning flow channel 135 and stops at the entrance of one of the cleaning flow channels 135, when the single first target A stops, the buffer liquid continues to flush for a set time, then the cleaning micro valve 125 is switched to the closed state, the second waste liquid micro valve 129 is switched to the open state, the buffer liquid with the cleaned single first target A flows to the pairing flow channel 137, when the single first target A enters the pairing flow channel 137, the first buffer micro valve 123 is switched to the closed state, at this time the single first target A will stay in the pairing flow channel 137.

[0112] Screening of the second target B: initially, the second micro valve 122, the second waste liquid micro valve 129 and the pairing micro valve 128 are all in the closed state, then the second micro valve 122 and the second waste liquid micro valve 129 are opened, the second carrier liquid containing the second target A flows through the second flow channel 132 to the second waste liquid flow channel 139, when a single second target B appears in the pairing flow channel 138, the second micro valve 122 is switched to the closed state, at this time the single second target B will stay in the pairing flow channel 137.

[0113] Pairing of the target: when the single first target A and the single second target B both stay in the pairing flow channel 137, the second buffer micro valve 127 and the pairing micro valve 128 are switched to the open state, the buffer liquid drives the single first target A and the single second target B in the pairing flow channel 137 to enter the oil flow channel 136 to encapsulate into a droplet.

[0114] The foregoing embodiment proposes a scheme of applying the independently arranged first buffer flow channel 133 and the second buffer flow channel 137. In other embodiments, the second buffer flow channel 137 can be omitted, and the function of the second buffer flow channel 137 is replaced by the first buffer flow channel 133. Specifically, the microfluidic system further comprises a second flow channel 132, an oil flow channel 136, and a pairing flow channel 138. The pairing flow channel 138 is connected to the oil flow channel 136. The first flow channel 131 and the second flow channel 132 are both connected to the pairing flow channel 138. The microfluidic system further comprises a pairing micro valve 128 arranged corresponding to the pairing flow channel 138 and a second micro valve 122 arranged corresponding to the second flow channel 132. The pairing micro valve 128 is used to control the opening and closing of the pairing flow channel 138, and the second micro valve 122 is used to control the opening and closing of the second flow channel 132. These flow channels and micro valves can be understood with reference to the foregoing embodiments.

[0115] When there is a single first target A from the first flow channel 131 and a single second target B from the second flow channel 132 in the pairing flow channel 138, the first micro valve 121, the second micro valve 122, the first waste micro valve 124, the second waste micro valve 129, and the cleaning micro valve 125 are all in the closed state, and the pairing micro valve 128 and the first buffer micro valve 123 are in the open state. The buffer in the first buffer micro valve 123 sends the single first target A and the single second target B in the pairing flow channel 138 into the oil in the oil flow channel 136 to form droplets, thereby also achieving the pairing of the targets.

[0116] When the microfluidic chip further comprises a second flow channel 132 and related micro valves, in some embodiments, the second target A comprises a detection microsphere. The structure of the detection microsphere comprises a marker core and a magnetic coating layer wrapped on the marker core. The marker core comprises a polymer core (such as polystyrene), and a detection marker (such as fluorescent dye APC, coomassie brilliant blue, and Nile blue chloride) modified on the surface of the polymer core. The shell layer is a magnetic coating layer, and the coating layer material is a ferromagnetic material such as ferroferric oxide. The above-mentioned detection microsphere forms a “sandwich” structure composed of a polymer core-a marker layer-a coating layer. On the outermost structure, the surface of the coating layer is also modified with a streptavidin (SA) group, which is used to bind a primer chain (the primer chain is modified with biotin, which can be combined with the streptavidin on the surface of the magnetic coating layer through biotin).

[0117] In some embodiments, the primer chain comprises an amplification primer (PCR Handle) as the starting position of PCR and sequencing, a barcode sequence (barcode) for labeling the identity of the cell, a molecular tag sequence (UMI) for excluding PCR bias interference, and a probe capture sequence (polydtVN). In addition, the 5' end of the primer chain is also modified with biotin.

[0118] In the sequencing, the existing fluorescent magnetic microspheres are connected with fluorescent dyes in a coupling manner, and the fluorescent intensity and uniformity are low, and the number of linkers on the surface of the microspheres is reduced, thereby affecting the subsequent biological reaction. In the utility model, the detection microspheres embed the detection markers in the magnetic shell, can contain more markers, and the markers are more uniformly distributed. Moreover, the connection between the detection microspheres and the primer chain in the utility model is that the SA group on the surface of the microsphere coating is connected with the 5' end of the primer chain through the streptavidin-biotin affinity reaction, and a disulfide bond is formed, the combination is more compact, which also allows the detection microspheres to carry more primer chains (for example, 5*10 7 to 2*10 8 pairs), and then capture more mRNA released after cracking, and improve the sequencing efficiency. At the same time, the primer chain and the detection microspheres can be separated by using a reducing agent, which is simple and convenient.

[0119] In some embodiments, the detection microspheres have a size of 10-20 μm, preferably 15 μm, and are suitable for single-cell sequencing pairing systems for fluorescent identification.

[0120] On the basis of the first embodiment, in some embodiments, the microfluidic system further comprises a power element such as a pump for driving the buffer flow. In some specific embodiments, the microfluidic system comprises a high-speed pump, which can realize high-speed flow and stopping of the buffer, thereby adapting to high-speed pairing.

[0121] On the basis of the first embodiment, in some embodiments, with reference to Figure 1 , the second waste liquid channel 139 is located between the first channel 131 and the second channel 132 along the extension direction of the pairing channel 138, so that the first carrier liquid does not drive the single second target object B which has been stationary when it is discharged, and similarly, the second carrier liquid does not drive the single second target object A which has been stationary when it is discharged, and the discharge of the first carrier liquid and the second carrier liquid can be synchronized.

[0122] On the basis of the first embodiment, in some embodiments, with reference to Figure 1 , the first channel 131 and the second channel 132 are located on the same side of the pairing channel 138, and the second waste liquid channel 139 is located on the other side of the pairing channel 138. In specific embodiments shown in Figure 1 , the first channel 131 and the second channel 132 are located on the upper side of the pairing channel 138, and the second waste liquid channel 139 is located on the lower side of the pairing channel 138, so that the first carrier liquid and the second carrier liquid can flow in substantially the same direction, facilitating the discharge of waste liquid.

[0123] On the basis of the first embodiment, in some embodiments, with reference to Figure 1The first portion of the first flow channel 131 that is connected to the paired flow channel 138 is intersected with the paired flow channel 138, specifically as shown in the reference. Figure 1 In the illustrated embodiment, the first portion is perpendicular to the mating channel 138.

[0124] Based on the first embodiment, in some embodiments, reference is made to Figure 1 The second portion of the second flow channel 132, which is at least connected to the mating flow channel 138, is intersected with the mating flow channel 138, as specifically referred to in the reference section. Figure 1 In the embodiment shown, the second portion is perpendicular to the mating channel 138.

[0125] Based on the first embodiment, in some embodiments, reference is made to Figure 1 The third part of the second waste liquid flow channel 139, which is at least connected to the paired flow channel 138, is arranged to intersect with the paired flow channel 138. Specifically, in the embodiment shown in Reference 1, the third part is perpendicular to the paired flow channel 138.

[0126] Based on the first embodiment, in some embodiments, reference is made to Figure 1 The fourth portion of the second buffer solution channel 137, which is at least connected to the paired channel 138, is coaxially arranged with the paired channel 138. Thus, the buffer solution can enter the paired channel 138 in the same direction and carry the single first target A and the single second target B into the oil. It should be noted that in this embodiment, the second buffer solution channel 137 and the paired channel 138 can be two parts of a single channel. Figure 1 As shown in the figure, the left side of the vertical straight channel is the pairing channel 138, and the right side is the second buffer channel 137. For ease of reading, the range of the pairing channel 138 is roughly marked by a dashed box in the figure. However, the dashed box should not be interpreted as a specific limitation on the shape and length of the pairing channel 138.

[0127] It is understood that the above embodiments can be combined, that is, the first part, the second part and the third part are all arranged to intersect with the mating flow channel, while the fourth part is arranged coaxially with the mating flow channel 138.

[0128] The microfluidic chips mentioned in the foregoing embodiments can be applied to single-cell sequencing, cell screening, cell interaction detection, cell omics analysis, proteomics analysis, and the preparation of cell therapy products or cell drugs.

[0129] Based on the first embodiment, in some embodiments of this utility model, reference is made to Figure 5 The microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 stacked sequentially. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS).

[0130] The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 136, the second buffer solution flow channel 137, the second waste liquid flow channel 139 and the pairing flow channel 138.

[0131] On the basis of the first embodiment, with reference to Figure 5 In some embodiments of the utility model, the microfluidic system includes a microfluidic chip 100, the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 which are sequentially stacked, the base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS).

[0132] The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 136, the second buffer solution flow channel 137, the second waste liquid flow channel 139 and the pairing flow channel 138.

[0133] On the basis of the first embodiment, in some embodiments of the utility model, the first target object A is a cell, and the second target object B is a microsphere.

[0134] On the basis of the first embodiment, in some embodiments of the utility model, the first target object A is a first cell, and the second target object B is a second cell, which is used to study the interaction effect between cells.

[0135] The second embodiment of the utility model provides a microfluidic system, which includes a detection module 200 and the microfluidic chip 100 of each of the foregoing embodiments. Figure 1, the first flow channel 131 has a first identification position C, the detection module 200 is configured to identify a single first target object A at the first identification position C, wherein when the detection module 200 identifies the single first target object A, the first micro valve 121 and the first waste liquid micro valve 124 are switched to the closed state to enable the single first target object A to be located in the first region 1311.

[0136] On the basis of the second embodiment, in some embodiments, when the detection module 200 does not identify the single first target object A, the first micro valve 121 and the first waste liquid micro valve 124 are kept in the open state, and the first buffer liquid micro valve 123 and the cleaning micro valve 125 are kept in the closed state, so that the liquid in the first flow channel 131 can flow out through the first waste liquid flow channel 134.

[0137] Correspondingly, the detection module 200 in some embodiments can also identify a single second target object B, and when the detection module 200 does not identify the single second target object A, the second micro valve 122 and the second waste liquid micro valve 129 are kept in the open state, so that the liquid in the second flow channel 132 can flow out through the second waste liquid flow channel 139.

[0138] When a single first target object A is identified by the detection module, in some embodiments of the utility model, the detection module is specifically a visual detection module, which includes a camera and a controller, and the controller is configured to control the camera to take an image. In this embodiment, the image taken by the camera at least includes a first image of the first flow channel 131, and after the camera takes the image, the controller is further configured to identify the single first target object A based on the first image.

[0139] Correspondingly, the detection module 200 in some embodiments can also identify a single second target object B, and the image taken by the camera also includes a second image of the second flow channel 132, and the controller is further configured to identify the single second target object B based on the second image.

[0140] In the above process, after the image captured by the camera is transmitted to the controller, the controller detects the target in the detection area (for example, an area with a length of 200 pixels and a width of 200 pixels), and classifies the cropped target image through a model trained by a convolutional neural network, judges according to the output result of the classification, and controls the corresponding micro valve.

[0141] When the detection module identifies a single first target object A through the image, in some embodiments of the utility model, the image taken by the camera at least also includes a third image of the matching flow channel 138, and the controller is configured to identify whether there is a single first target object A in the matching flow channel 138 based on the third image, in other words, whether the single first target object A enters the matching flow channel 138 can also be verified by the image taken by the camera in this embodiment.

[0142] Correspondingly, the detection module 200 in some embodiments can also identify the single second target object B, and the image captured by the camera at least includes a third image of the matching flow channel 138, and the controller is configured to identify whether the single second target object B is present in the matching flow channel 138 based on the third image, in other words, whether the single second target object B enters the matching flow channel 138 can also be verified by the image captured by the camera in the embodiment.

[0143] It should be noted that the above embodiments can be combined, for example, the image captured by the camera includes the first image, the second image and the third image, in this way, the controller can realize the combined operation through the same image, for example, simultaneously identifying the single first target object A and the single first target object B, or identifying the single first target object A and determining whether the single second target object B has reached the matching flow channel 138, or identifying the single first target object B and determining whether the single first target object A has reached the matching flow channel 138, or determining whether the single first target object A and the single second target object B have reached the matching flow channel 138.

[0144] When the single first target object A is identified by the detection module, in some embodiments of the utility model, the detection module is specifically a fluorescence detection module, which includes a first light source, a first light detection device and a controller, the controller is configured to control the first light source to emit first detection light to the first flow channel 131, the first detection light can excite first fluorescence after irradiating the single first target object A, and the first light detection device can receive the first fluorescence excited by the single first target object A, for example, the first light source is a laser, and the first light detection device is a photomultiplier tube, when the first fluorescence emitted by the single first target object A is received, the photomultiplier tube can convert the light signal into an electric signal and then transmit it to the controller.

[0145] For example, referring to Figure 1 , the first light source projects the first detection light to the first identification site C of the first flow channel 131, when no cell reaches the first identification site C, the first light detection device will not receive the light signal, when the cell reaches the first identification site C, the cell is excited by the first detection light to generate fluorescence, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target object A.

[0146] Correspondingly, the detection module 200 in some embodiments can also identify the single second target object B, and in some embodiments of the utility model, the detection module is specifically a fluorescence detection module, which includes a second light source, a second light detection device and a controller, the controller is configured to control the second light source to emit second detection light to the second flow channel 132, the second detection light can excite second fluorescence after irradiating the single second target object B, and when the second light detection device detects the second fluorescence, the controller identifies the single second target object B.

[0147] For example, referring to Figure 1 The second light source projects second detection light to the third identification site E of the second flow channel 132. When no cell reaches the third identification site E, the second light detection device does not receive a light signal. When a cell reaches the third identification site E, the cell is excited by the second detection light to generate fluorescence. When the second light detection device detects the second fluorescence, the detection device identifies a single second target object A.

[0148] It should be noted that the first light source and the second light source can be lasers of different wavelengths.

[0149] For example, referring to Figure 1 The detection module 200 further includes a first light transmission device 210 and a second light transmission device 220. The first light transmission device 210 is configured to receive the first detection light of the first light source and transmit the first detection light to the first identification site C. The second light transmission device 220 is configured to receive the first fluorescence and transmit the first fluorescence to the first light detection device. For example, the first light transmission device 210 and the second light transmission device 220 are optical fibers inserted into the microfluidic chip, and one end of each of the optical fibers faces the first identification site C.

[0150] For example, referring to Figure 1 The first flow channel 131 includes a first flow channel segment 1313 and a second flow channel segment 1314 arranged in sequence along a flow direction. The first buffer flow channel 133, the first waste liquid flow channel 134, and the cleaning flow channel group are all connected to the second flow channel segment 1314. The axis of the first flow channel segment 1313 intersects the axis of the second flow channel segment 1314. For example, the first flow channel segment 1313 and the second flow channel segment 1314 are both straight segments. The first identification site C is arranged at the second flow channel segment 1314. For example, the first identification site C is arranged at one end of the second flow channel segment 1314 close to the first flow channel segment 1313.

[0151] In this embodiment, the axis of the first light transmission device 210 intersects the axis of the second light transmission device 220. Specifically, the first light transmission device 210 is arranged on a side of the first flow channel segment 1313 away from the second flow channel segment 1314 and points to the second flow channel segment 1314. For example, Figure 1 In this embodiment, the second flow channel segment 1314 in the first flow channel segment 1313 is located on the lower side of the first flow channel segment 1313, and the first light transmission device 210 is arranged on the upper side of the first flow channel segment 1313. The second light transmission device 220 corresponding to the first identification site C is arranged at the second flow channel segment 1314. For example, the second light transmission device 220 is flush with or substantially flush with the first identification site C.

[0152] Based on the above, the first light conducting device 210 and the second light conducting device 220 are arranged in a staggered manner, so that multiple identification positions can be arranged, thereby adapting to the identification of different first target objects. For example, along the flow direction of the first carrier liquid, multiple first identification positions C are arranged in sequence on the second flow channel section 1314, and multiple second light conducting devices 220 are arranged corresponding to each first identification position C. The first carrier liquid contains multiple first target objects A, and different target objects A emit different fluorescent light, for example, different wavelengths of fluorescent light. When the first detection light emitted by the first light conducting device 210 irradiates on different first target objects A, different wavelengths of fluorescent light can be excited, and different fluorescent light can be received by the first light detection device, so that different first target objects A can be identified. That is, the embodiment facilitates the expansion of identification points, and one first light detection device can be used to realize the identification of multiple fluorescent light, which is helpful to simplify the structure and reduce the cost. It should be noted that, in order to avoid interference between the fluorescent light, a light filtering device can be arranged on the light transmission path of the corresponding second light conducting device 220 to filter out fluorescent light of other wavelength ranges.

[0153] In some embodiments, the axis of the first flow channel section 1313 and the second flow channel section 1314 are perpendicular, the axis of the first light conducting device 210 and the second light conducting device 220 are perpendicular, and the second light conducting device 220 is arranged on the side of the second flow channel section 1314 away from the first flow channel section 1313 and points to the first flow channel section 1313. For example, Figure 1 In some embodiments, the first flow channel section 1313 is arranged on the left side of the second flow channel section 1314, and the second light conducting device 220 is arranged on the right side of the second flow channel section 1314.

[0154] In some embodiments, referring to Figure 1 , along the flow direction of the first carrier liquid in the first flow channel 131, the first identification position C is located upstream of the first buffer liquid flow channel 133. Generally, the micro-valve for controlling the opening and closing of the flow channel has a certain response time. By arranging the first identification position C upstream of the first buffer liquid flow channel 133, the first target object A can be identified in advance, thereby facilitating the first identification position C to stay in the first region 1311. For example, the first identification position C is located on the upper side of the first buffer liquid flow channel 133.

[0155] In some embodiments, referring to Figure 6 , the first light conducting device 210 and the second light conducting device 220 can also be arranged on opposite sides of the first flow channel 131, and the first light conducting device 210 and the second light conducting device 220 are coaxially arranged. In this way, the excited fluorescent light can be more easily transmitted by the second light conducting device 220. It should be noted that, in order to avoid interference of the first detection light, a light filtering device can be arranged on the light transmission path of the second light conducting device 220 to filter out the first detection light.

[0156] The detection module 200 in some embodiments can also identify a single second target object B, which can also apply the aforementioned light transmission device for light transmission, which is not described in detail here.

[0157] When a single first target object A is identified by the detection module, in some embodiments of the utility model, the detection module is specifically an electrode detection module, which includes a first detection electrode and a controller. The first detection electrode extends into the first flow channel 131. When a single first target object A passes through the first detection electrode, the first detection electrode will generate a corresponding signal. The controller is configured to identify a single first target object A based on the signal detected by the first detection electrode. Specifically, the first detection electrode includes a positive electrode and a negative electrode, which are arranged side by side. For example, the first detection electrode can be a metal layer arranged between the control layer 120 and the flow channel layer 130 of the microfluidic chip 100. In addition, in this embodiment, the signal detected by the first detection electrode can be the change of amplitude and phase difference. It should be noted that the microsphere in this embodiment can be a magnetic microsphere, which can be adsorbed by a magnetic piece for recycling.

[0158] Correspondingly, the detection module 200 in some embodiments can also identify a single second target object B. In some embodiments of the utility model, the detection module is specifically an electrode detection module, which includes a second detection electrode and a controller. The second detection electrode extends into the second flow channel 132. The controller is configured to identify a single second target object B based on the signal detected by the second detection electrode. The second detection electrode can be understood with reference to the first detection electrode.

[0159] When a single first target object A is identified by the detection module, in some embodiments of the utility model, when the detection module identifies a single first target object A, the first micro valve 121 is switched from an open state to a closed state after a set time delay, so that the single first target object A stays in the first region 1311. For reference Figure 1 , the first identification position C for identifying a single first target object A and the first region 1311 have a certain distance. In this embodiment, the first micro valve 121 is closed in a delayed manner to ensure that the single first target object A can enter the first region 1311. It should be noted that the set time of the delay can be determined according to the distance between the identification position and the first region 1311 and the flow rate of the first carrier liquid.

[0160] Correspondingly, the detection module 200 in some embodiments can also identify a single second target object B. In some embodiments of the utility model, when the detection module identifies a single second target object B, the second micro valve 122 is switched from an open state to a closed state after a set time delay, so that the single second target object B enters the matching flow channel 138 from the second flow channel 132. For reference Figure 1The third identification position E of the single second target object B is away from the matching flow channel 138, and the second micro valve 122 is closed in a delayed manner to ensure that the single second target object B can enter the matching flow channel 138. It should be noted that the setting time of the delay can be determined according to the distance between the identification position and the matching flow channel 138 and the flow rate of the second carrier liquid.

[0161] The third embodiment of the utility model provides a kind of microfluidic system, it includes detection module 200 and the microfluidic chip 100 of each embodiment described above, refer to Figure 7 The first flow channel 131 between the cleaning flow channel group and the matching flow channel 138 has a second identification position D, and the detection module 200 is configured to identify a single first target object A at the second identification position D, wherein when the detection module 200 identifies a single first target object A, the first micro valve 121 and the matching micro valve 128 are both in a closed state to keep the single first target object A in the matching flow channel 138. That is, the embodiment is used to further identify a single first target object A after a single first target object A has stopped at the inlet of the cleaning flow channel 135 and cleaning is completed to ensure that a single first target object A can stay in the matching flow channel 138.

[0162] In other embodiments, the second flow channel 132 has a third identification position E, and the detection module 200 is configured to identify a single second target object B at the third identification position E, wherein when the detection module 200 identifies a single second target object B, the second micro valve 122 and the matching micro valve 128 are both in a closed state to keep the single second target object B in the matching flow channel 138.

[0163] It should be noted that the detection module in the foregoing embodiments can be the visual detection module, the fluorescence detection module or the electrode detection module mentioned in the second embodiment.

[0164] On the basis of the third embodiment, in some embodiments of the utility model, refer to Figure 7 The first flow channel 131 has a first identification position C, and the detection module 200 is configured to identify a single first target object A at the first identification position C, wherein when the detection module 200 identifies a single first target object A, the first micro valve 121 and the matching micro valve 128 are both switched to a closed state to make the single first target object A located in the first region 1311. The first identification position C can be understood with reference to the second embodiment described above.

[0165] The microfluidic system of the embodiment further comprises a carrier platform configured to carry the microfluidic chip 100 and movable between the first position and the second position. In some specific embodiments, the carrier platform is movable in a horizontal direction so as to switch between the first position and the second position. Further, the carrier platform is linearly movable in the horizontal direction so as to switch between the first position and the second position. For example, the carrier platform is connected with a driving mechanism, which comprises a driving seat linearly movable in a horizontal plane and a power mechanism configured to drive the driving seat to move, and the carrier platform is connected with the driving seat.

[0166] In the embodiment, the detection module can be the aforementioned visual detection module or the fluorescent detection module. When the carrier platform is located at the first position, the detection module 200 is configured to identify the single first target object A at the first identification site C. When the carrier platform is located at the second position, the detection module 200 is configured to identify the single first target object A at the second identification site D. In other embodiments, the detection module 200 is configured to identify the single second target object B at the third identification site E. In other embodiments, the detection module 200 is configured to identify the single first target object A at the second identification site D and the single second target object B at the third identification site E at the same time. In this way, the two identifications of the single first target object A and / or the identification of the single first target object A and the single second target object B can be completed by one visual camera or one photoelectric sensor.

[0167] The fourth embodiment of the utility model provides a kind of processing method, it is applied to the screening of first target object A in microfluidic system, and microfluidic system includes microfluidic chip, and microfluidic chip includes first flow passage 131 and the washing flow passage group connected to first flow passage 131, and washing flow passage group includes at least two washing flow passages 135, at least two washing flow passages 135 are sequentially arranged along the flow direction of first carrying liquid in first flow passage 131, the diameter of the inlet of washing flow passage 135 is less than the diameter of first target object A, and microfluidic system can be understood with reference to the microfluidic system in the aforementioned second embodiment, third embodiment, but not limited to this, processing method includes the following steps:

[0168] Step one: along the flow direction of first carrying liquid, single first target object A is identified from first carrying liquid in the upstream of washing flow passage group. Wherein, it can be identified by image recognition, fluorescent identification or electrode identification in the aforementioned embodiments, for example, identification position can be understood with reference to the aforementioned first identification site C.

[0169] Step two: after identifying the single first target object A, the first stopping position upstream of the single first target object A and the second stopping position downstream of the cleaning flow channel group are closed to shut off the first flow channel 131. The first stopping position can be understood with reference to the position of the first micro valve 121 in the foregoing embodiments, and the second stopping position can be understood with reference to the second waste liquid micro valve 129 in the foregoing embodiments. It should be noted that the closing of the stopping position includes switching the stopping position from an open state to a closed state, such as switching the first micro valve 121 from an open state to a closed state, and keeping the stopping position in a closed state, such as keeping the second waste liquid micro valve 129 in a closed state. It should be further noted that when the single first target object A is continuously flowed by discharging the waste liquid through the first waste liquid flow channel 134 in step one, the first waste liquid flow channel 134 is switched to a closed state in this step.

[0170] Step three: a first buffer solution is introduced into the first flow channel 131 between the first stopping position and the second stopping position and upstream of the single first target object A. The first buffer solution carries the single first target object A to the inlet of one of the cleaning flow channels 135 and stops at the inlet, and the first buffer solution flows out through the other cleaning flow channels 135. The first buffer solution can be provided through the first buffer solution flow channel 133, for example. In some specific embodiments, when the single first target object A stops at the inlet, the first buffer solution continues to flush for a set time to remove non-target objects near the first target object A.

[0171] Step four: the cleaning flow channel 135 is closed, and the first flow channel 131 of the second stopping position is restored to flow, and the single first target object A is continuously carried by the first buffer solution. In this way, the screening of the single first target object and the removal of non-target objects can be achieved to avoid pollution from non-target objects.

[0172] On the basis of the fourth embodiment, in some embodiments of the utility model, the "continuously carrying the single first target object A by the first buffer solution" in the foregoing step four specifically refers to: after the single first target object A is carried to the target region by the first buffer solution, the input of the first buffer solution is stopped to stop the single first target object A in the target region. The target region can be understood with reference to the pairing flow channel 138 in the foregoing embodiments, that is, the present embodiment can be applied to the pairing of target objects.

[0173] In some specific embodiments, the microfluidic chip further includes a second flow channel 132, which can be understood according to the foregoing embodiments and is used for flowing a second carrier liquid containing a second target object B.

[0174] Based on the above scheme, the processing method further includes the following steps:

[0175] Step five: identifying the single second target object B from the second carrier liquid in the second flow channel 132, wherein the identification can be performed by image recognition, fluorescence recognition or electrode recognition in the foregoing embodiments, and the identification position can be understood with reference to the third identification position E in the foregoing embodiments.

[0176] Step six: after identifying the single second target object B, the third stopping position upstream of the single second target object B is in a closed state to shut off the second flow channel 132 along the flow direction of the second carrier liquid in the second flow channel 132, so as to stop the single second target object B in the target region. The third stopping position can be understood with reference to the position of the second micro valve 122 in the foregoing embodiments, and it should be noted that the stopping position in the closed state includes switching the stopping position from the open state to the closed state, for example, switching the second micro valve 122 from the open state to the closed state.

[0177] Step seven: after the single first target object A and the single second target object B are stopped in the target region, the second buffer solution is directly introduced into the target region, and the single first target object A and the single second target object B in the target region are sent into the oil liquid by the second buffer solution to form droplets. The second buffer solution can be provided by, for example, the second buffer solution flow channel 137.

[0178] In other embodiments, after the single first target object A and the single second target object B are stopped in the target region, the first buffer solution is introduced into the first flow channel 131 between the first stopping position and the second stopping position, and the single first target object A and the single second target object B in the target region are sent into the oil liquid by the first buffer solution to form droplets, that is, the same first buffer solution is used to send the single first target object A and the single second target object B into the oil liquid.

[0179] It should be noted that steps five and six can be performed before step two or after step three.

[0180] The embodiments of the utility model are described in detail above in combination with the drawings, but the utility model is not limited to the above embodiments, and various changes can be made within the knowledge range of ordinary skilled in the art without departing from the purpose of the utility model. In addition, the embodiments of the utility model and the features in the embodiments can be combined with each other without conflict.

Claims

1. A microfluidic chip for screening of a first target, characterized in that, The microfluidic chip comprises a first flow channel, a first buffer solution flow channel, a first waste liquid flow channel and a cleaning flow channel group which are respectively communicated with the first flow channel, the first flow channel is used for flowing liquid containing the first target object, along the flow direction of the liquid in the first flow channel, the first waste liquid flow channel and the cleaning flow channel group are both arranged downstream of the first buffer solution flow channel, the cleaning flow channel group comprises at least two cleaning flow channels arranged in sequence along the flow direction, the diameter of the inlet of the cleaning flow channel is smaller than the diameter of the first target object; The microfluidic chip further comprises a first micro valve corresponding to the first flow channel, a first buffer solution micro valve corresponding to the first buffer solution flow channel, a first waste liquid micro valve corresponding to the first waste liquid flow channel, and a cleaning micro valve corresponding to each cleaning flow channel, the first micro valve is used for controlling the opening and closing of the first flow channel, the first buffer solution micro valve is used for controlling the opening and closing of the first buffer solution flow channel, the first waste liquid micro valve is used for controlling the opening and closing of the first waste liquid flow channel, and the cleaning micro valve is used for controlling the opening and closing of each cleaning flow channel; Wherein, the first flow channel between the first buffer solution flow channel and the cleaning flow channel group is defined as a first region, and the microfluidic chip is configured to: when the first micro valve and the first waste liquid micro valve are in an open state, so that a single first target object flows to the first region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer solution micro valve and the cleaning micro valve are in an open state, so that the single first target object flows to the inlet of one of the cleaning flow channels and stops at the inlet, and the liquid in the first region flows out through the other cleaning flow channels.

2. The microfluidic chip of claim 1, wherein, The first waste liquid flow channel and the cleaning flow channel are independent flow channels, and the diameter of the first waste liquid flow channel is greater than the diameter of the cleaning flow channel.

3. The microfluidic chip of claim 2, wherein, Along the flow direction, the first buffer solution flow channel, the first waste liquid flow channel and the cleaning flow channel group are arranged in sequence; Wherein, the first flow channel between the first buffer solution flow channel and the first waste liquid flow channel is defined as a second region, and when the first micro valve and the first waste liquid micro valve are in an open state, and a single first target object flows to the first region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer solution micro valve and the cleaning micro valve are in an open state, which comprises: when the first micro valve and the first waste liquid micro valve are in an open state, and a single first target object flows to the second region, the first micro valve and the first waste liquid micro valve are switched to a closed state, and the first buffer solution micro valve and the cleaning micro valve are switched to an open state.

4. The microfluidic chip of claim 1, wherein, At least one of the cleaning flow channels is the first waste liquid flow channel, and the cleaning micro valve is the first waste liquid micro valve.

5. The microfluidic chip of claim 1, wherein, The cleaning flow channel comprises a first cleaning section communicated with the first flow channel, the first cleaning section has the inlet at one end facing the first flow channel, and along the flow direction of the liquid in the cleaning flow channel, the cross-sectional area of the first cleaning section gradually increases from the end having the inlet.

6. The microfluidic chip of claim 5, wherein, The cleaning flow channel further comprises a second cleaning section in communication with the first cleaning section, and a cross-sectional area of the second cleaning section is greater than or equal to a maximum cross-sectional area of the first cleaning section.

7. The microfluidic chip of claim 1, wherein, The diameter of the inlet of the first waste liquid flow channel is 5-10 microns.

8. The microfluidic chip of claim 1, wherein, The microfluidic chip further comprises a connecting flow channel, one end of the connecting flow channel being in communication with the first flow channel, and the other end being in communication with each cleaning flow channel, and a length of the connecting flow channel is 3-8 microns in a flow direction of liquid in the connecting flow channel.

9. The microfluidic chip of claim 1, wherein, The microfluidic chip further comprises a second flow channel, an oil liquid flow channel, a second buffer liquid flow channel, and a pairing flow channel, the pairing flow channel being in communication with the oil liquid flow channel, the first flow channel, the second flow channel, and the second buffer liquid flow channel all being in communication with the pairing flow channel, and the second flow channel being used for flowing liquid containing a second target object. The microfluidic chip further comprises a pairing micro valve corresponding to the pairing flow channel, a second micro valve corresponding to the second flow channel, an oil liquid micro valve corresponding to the oil liquid flow channel, and a second buffer liquid micro valve corresponding to the second buffer liquid flow channel, the pairing micro valve being used for controlling opening and closing of the pairing flow channel, the second micro valve being used for controlling opening and closing of the second flow channel, the oil liquid micro valve being used for controlling opening and closing of the oil liquid flow channel, and the second buffer liquid micro valve being used for controlling opening and closing of the second buffer liquid flow channel. When the pairing flow channel contains the single first target object from the first flow channel and the single second target object from the second flow channel, the first micro valve, the second micro valve, the first buffer liquid micro valve, the first waste liquid micro valve, and the cleaning micro valve are all in a closed state, and the pairing micro valve and the second buffer liquid micro valve are in an open state, so as to send the single first target object and the single second target object in the pairing flow channel into oil liquid in the oil liquid flow channel to form a droplet.

10. The microfluidic chip of claim 9, wherein, The microfluidic chip further comprises a second waste liquid flow channel and a second waste liquid micro valve corresponding to the second waste liquid flow channel, the second waste liquid flow channel being in communication with the pairing flow channel, and the second waste liquid micro valve being used for controlling opening and closing of the second waste liquid flow channel, and the microfluidic chip is further configured such that, when the single first target object stops at the inlet of one of the cleaning flow channels, the first micro valve, the first waste liquid micro valve, the cleaning micro valve, the second buffer liquid flow channel, and the pairing micro valve are all in a closed state, and the first buffer liquid micro valve and the second waste liquid micro valve are in an open state, liquid in the first flow channel can flow out through the pairing flow channel and the second waste liquid flow channel, so as to make the single first target object enter the pairing flow channel from the first flow channel.

11. The microfluidic chip of claim 10, wherein, The microfluidic chip is further configured to: when the single first target stops at the inlet of one of the washing flow channels, and the first buffer micro valve and the washing micro valve remain in the open state for a set time, the washing micro valve switches to the closed state, and the second waste liquid micro valve switches to the open state, so that the single first target enters the pairing flow channel from the first flow channel.

12. The microfluidic chip of claim 9, wherein, The microfluidic chip further comprises a second waste liquid flow channel and a second waste liquid micro valve corresponding to the second waste liquid flow channel, the second waste liquid flow channel being in communication with the pairing flow channel, and the second waste liquid micro valve being used to control the opening and closing of the second waste liquid flow channel. When the first micro valve, the first waste liquid micro valve, the washing micro valve and the pairing micro valve are all in the closed state, and the first buffer micro valve and the second waste liquid micro valve are in the open state, the liquid in the first flow channel can flow out through the pairing flow channel and the second waste liquid flow channel. When the pairing micro valve is in the closed state, and the second micro valve and the second waste liquid micro valve are in the open state, the liquid in the second flow channel can flow out through the pairing flow channel and the second waste liquid flow channel.

13. The microfluidic chip of claim 1, wherein, The microfluidic chip further comprises a second flow channel, an oil flow channel and a pairing flow channel, the pairing flow channel being in communication with the oil flow channel, and the first flow channel and the second flow channel both being in communication with the pairing flow channel. The microfluidic chip further comprises a pairing micro valve corresponding to the pairing flow channel and a second micro valve corresponding to the second flow channel, the pairing micro valve being used to control the opening and closing of the pairing flow channel, and the second micro valve being used to control the opening and closing of the second flow channel. When the pairing flow channel contains the single first target from the first flow channel and the single second target from the second flow channel, the first micro valve, the second micro valve, the first waste liquid micro valve and the washing micro valve are all in the closed state, and the pairing micro valve and the first buffer micro valve are in the open state, so that the buffer liquid in the first buffer micro valve sends the single first target and the single second target in the pairing flow channel into the oil liquid in the oil flow channel to form a droplet.

14. The microfluidic chip of claim 9, wherein, The second target is a detection microsphere, and the detection microsphere comprises a marker core and a magnetic coating layer covering the marker core; wherein the marker core comprises a polymer core and a detection marker on the surface of the polymer core; and the surface of the magnetic coating layer is combined with a primer chain.

15. The microfluidic chip of claim 14, wherein, The surface of the magnetic coating layer is modified with streptavidin, and the primer chain is modified with biotin, and the primer chain is combined with the streptavidin on the surface of the magnetic coating layer through biotin.

16. The microfluidic chip of claim 14, wherein, The number of primer strands bound to the surface of the magnetic coating layer is 5 x 10 7 2 x 10 8 strips.

17. The microfluidic chip of claim 14, wherein, The polymer comprises a copolymer or homopolymer formed by at least one monomer of styrene, acrylic acid, acrylate or methacrylate.

18. The microfluidic chip of claim 14, wherein, The magnetic coating layer comprises at least one of magnetite, ferroferric oxide or ferrite material.

19. The microfluidic chip of claim 14, wherein, The detection marker comprises a fluorescent detection marker.

20. The microfluidic chip of claim 19, wherein, The fluorescent detection marker comprises at least one of APC, coomassie brilliant blue and Nile blue chloride.

21. The microfluidic chip of claim 14, wherein, The diameter of the detection microsphere is 10-20 μm.

22. Use of the microfluidic chip of any one of claims 1 to 21 in single cell sequencing, cell screening, cell interaction detection, cell omics analysis, proteomics analysis, preparation of cell therapy products or cell drugs.

23. A microfluidic system comprising: the microfluidic chip of any one of claims 1 to 21; a detection module; wherein the first flow channel has a first identification site, and the detection module is configured to identify the single first target object at the first identification site, wherein when the detection module identifies the single first target object, the first microvalve and the first waste microvalve are switched to a closed state to enable the single first target object to be located in the first region.

24. The microfluidic system of claim 23, wherein, When the detection module does not identify the single first target object, the first microvalve and the first waste microvalve are kept in an open state, and the first buffer microvalve and the cleaning microvalve are kept in a closed state, to enable the liquid in the first flow channel to flow out through the first waste flow channel.

25. The microfluidic system of claim 23, wherein, The detection module comprises a camera and a controller, the controller is configured to control the camera to capture a first image of the first identification site, and the controller is further configured to identify the single first target object based on the first image.

26. The microfluidic system of claim 23, wherein, The detection module comprises a first light source, a first light detection device and a controller, the controller is configured to control the first light source to emit first detection light to the first identification site, the first detection light is capable of exciting first fluorescence after irradiating the single first target object, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target object.

27. The microfluidic system of claim 26, wherein, The detection module further comprises a first light transmission device and a second light transmission device, the first light transmission device is configured to receive the first detection light of the first light source and transmit the first detection light to the first identification site, and the second light transmission device is configured to receive the first fluorescence and transmit the first fluorescence to the first light detection device.

28. The microfluidic system of claim 27, wherein, The first flow channel comprises a first flow channel segment and a second flow channel segment arranged in sequence along the flow direction, the first buffer flow channel, the first waste flow channel and the cleaning flow channel group are all communicated to the second flow channel segment, the axis of the first flow channel segment and the second flow channel segment is arranged perpendicularly, and the first identification site is arranged in the second flow channel segment, wherein the first light transmission device is arranged on the side of the first flow channel segment away from the second flow channel segment and points to the second flow channel segment, the second light transmission device is arranged in the second flow channel segment corresponding to the first identification site, and the axis of the first light transmission device and the second light transmission device is arranged perpendicularly.

29. The microfluidic system of claim 28, wherein, The axis of the first flow channel segment and the second flow channel segment is perpendicular, the axis of the first light transmission device and the second light transmission device is perpendicular, and the second light transmission device is arranged on the side of the second flow channel segment away from the first flow channel segment and points to the first flow channel segment.

30. The microfluidic system of claim 27, wherein, The first light-conducting device and the second light-conducting device are arranged on opposite sides of the first flow channel, and the first light-conducting device and the second light-conducting device are coaxially arranged.

31. The microfluidic system of claim 23, wherein, The detection module comprises a first detection electrode and a controller, the first detection electrode is arranged at the first identification position and extends into the first flow channel, and the controller is configured to identify the single first target based on a signal detected by the first detection electrode.

32. The microfluidic system of any one of claims 23-31, wherein, In the flow direction, the first identification position is located upstream of the first buffer flow channel.

33. A microfluidic system, comprising: the microfluidic chip according to any one of claims 9 to 21; a detection module; wherein the first flow channel between the cleaning flow channel group and the paired flow channel has a second identification position, and the detection module is configured to identify the single first target at the second identification position, wherein when the detection module identifies the single first target, the first microvalve and the paired microvalve are both in a closed state to keep the single first target in the paired flow channel; and / or the second flow channel has a third identification position, and the detection module is configured to identify the single second target at the third identification position, wherein when the detection module identifies the single second target, the second microvalve and the paired microvalve are both in a closed state to keep the single second target in the paired flow channel.

34. The microfluidic system of claim 33, wherein, The first flow channel has a first identification position, and the detection module is configured to identify the single first target at the first identification position, wherein when the detection module identifies the single first target, the first microvalve and the paired microvalve are both switched to a closed state to keep the single first target in the first region; The microfluidic system further comprises a carrier platform, the carrier platform is used to carry the microfluidic chip and can move between a first position and a second position; wherein when the carrier platform is located at the first position, the detection module is configured to identify the single first target at the first identification position; when the carrier platform is located at the second position, the detection module is configured to identify the single first target at the second identification position, and / or the detection module is configured to identify the single second target at the third identification position.

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