Microfluidic system for target object pairing, and pairing method

Abstract

Disclosed in the present invention are a microfluidic system for target object pairing, and a pairing method. The microfluidic system comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer solution flow channel, a pairing flow channel, a pairing microvalve, a first microvalve, a second microvalve and a buffer solution microvalve; the pairing flow channel is communicated with the oil liquid flow channel; the first flow channel, the second flow channel and the buffer solution flow channel are all communicated with the pairing flow channel; and when a single first target object and a single second target object are present in the pairing flow channel, the first microvalve and the second microvalve are in a closed state, and the pairing microvalve and the buffer solution microvalve are in an open state, so that a buffer solution in the buffer solution flow channel delivers the single first target object and the single second target object in the pairing flow channel into an oil liquid in the oil liquid flow channel to form liquid drops. The present invention can completely prevent another first target object and / or another second target object from entering the liquid drops, thereby facilitating the improvement of the success rate of packaging, and reducing cell loss caused by multi-packaging.

Description

Microfluidic system and pairing method for target pairing Technical Field

[0001] The present invention relates to the field of single-cell sequencing technology, and in particular to a microfluidic system and a pairing method for target pairing. Background Art

[0002] Single-cell RNA sequencing technology (scRNA-seq) reveals the heterogeneity of cells within tissues. Compared with traditional gene sequencing technology, single-cell sequencing technology has the advantages of high precision and high resolution, can provide information at the single-cell level, reveal the heterogeneity and complexity of expression within tissues, and has wide applications in fields such as cancer, reproduction, immunity and development. Figure 1 shows a pairing system for pairing a single first target with a single second target, including a first flow channel 1, a second flow channel 2, an oil flow channel 3, a waste flow channel 4, a sample flow channel 5 and a plurality of microvalves arranged corresponding to each flow channel. The microvalves can control the on and off of the corresponding flow channels. The first flow channel 1 has a first stop area 11, and the second flow channel 2 has a second stop area 21. When in use, a first liquid containing a first target is injected into the first flow channel 1, and a second liquid containing a second target is injected into the second flow channel 2. If no single first target appears in the first stop area 11, the first liquid is discharged through the waste flow channel 4. Correspondingly, if no single second target appears in the second stop area 21, the second liquid is also discharged through the waste flow channel 4. If a single first target object appears in the first stop area 11, the flow of the first liquid in the first flow channel 1 is cut off by the corresponding microvalve, so that the single first target object stops in the first stop area 11. Correspondingly, if a single second target object appears in the second stop area 21, the flow of the second liquid in the second flow channel 2 is cut off by the corresponding microvalve, so that the single second target object stops in the second stop area 21. After the single first target object and the single second target object have both stopped at the corresponding stop positions, the waste liquid flow channel 4 is cut off and the oil flow channel 3 and the sample flow channel 5 are opened, and then the first flow channel 1 and the second flow channel 2 are opened, so that the single first target object and the single second target object are respectively sent into the oil through the first liquid and the second liquid to form droplets, and the droplets then flow out through the sample flow channel 5. The above solution has the following problems:

[0003] 1. The power sources for pushing a single first target and a single second target into the oil come from the first liquid and the second liquid, respectively. Therefore, the following problems may arise: 1. When the first liquid pushes a single first target, subsequent first targets are also encapsulated into the droplet; 2. When the second liquid pushes a single second target, subsequent second targets are also encapsulated into the droplet; 3. When the first liquid pushes a single first target, and when the second liquid pushes a single second target, subsequent first targets and subsequent second targets are encapsulated into the droplet together, resulting in the formed droplet including multiple first targets and / or multiple second targets, causing multiple encapsulation, thereby affecting subsequent detection.

[0004] 2. The scheme shown in Figure 1 will generate a large number of empty droplets, which need to be sorted from normal droplets to avoid mixing. Therefore, the processing speed is slow and the efficiency is low.

[0005] Summary of the Invention

[0006] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a microfluidic system for target pairing.

[0007] The present invention also proposes a pairing method.

[0008] According to the first embodiment of the present invention, the microfluidic system for target pairing includes a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, and a pairing flow channel, wherein the pairing flow channel is connected to the oil flow channel, and the first flow channel, the second flow channel, and the buffer flow channel are all connected to the pairing flow channel;

[0009] The microfluidic system further includes a paired microvalve provided corresponding to the paired flow channel, a first microvalve provided corresponding to the first flow channel, a second microvalve provided corresponding to the second flow channel, and a buffer microvalve provided corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel;

[0010] When a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets.

[0011] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects:

[0012] This embodiment is provided with a separate buffer flow channel, which pushes a single first target object A and a single second target object B into the oil liquid through the buffer, without the need to push the single first target object A and the single second target object B through the first liquid and the second liquid. Therefore, the first flow channel and the second flow channel can be maintained in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0013] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel and a waste liquid microvalve corresponding to the waste liquid flow channel, the waste liquid flow channel is connected to the paired flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel;

[0014] Wherein, when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel;

[0015] And / or, when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

[0016] In other embodiments of the present invention, the first flow channel, the second flow channel, the buffer flow channel, and the waste liquid flow channel are all located on a side of the paired microvalve away from the oil flow channel.

[0017] In other embodiments of the present invention, the first flow channel and the second flow channel are located on the same side of the paired flow channel, and the waste liquid flow channel is located on the other side of the paired flow channel.

[0018] In other embodiments of the present invention, the microfluidic system further comprises at least one of the following solutions:

[0019] At least a first portion of the first flow channel that is in communication with the paired flow channel is arranged to intersect with the paired flow channel;

[0020] At least a second portion of the second flow channel that is in communication with the paired flow channel is arranged to intersect with the paired flow channel;

[0021] At least a third portion of the waste liquid flow channel that is in communication with the matching flow channel is arranged to intersect with the matching flow channel.

[0022] In other embodiments of the present invention, at least a fourth portion of the buffer flow channel that is in communication with the mating flow channel is coaxially arranged with the mating flow channel.

[0023] In other embodiments of the present invention, along the extension direction of the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel.

[0024] In other embodiments of the present invention, the microfluidic system further includes a detection module, wherein the detection module is configured to identify a single first target object in the first flow channel, wherein, when the detection module identifies the single first target object, the first microvalve and the paired microvalve are both in a closed state to keep the single first target object in the paired flow channel;

[0025] And / or, the microfluidic system further includes a detection module, which is configured to identify a single second target object in the second flow channel, wherein, when the detection module identifies the single second target object, the second microvalve and the paired microvalve are both in a closed state to keep the single second target object in the paired flow channel.

[0026] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel and a waste liquid microvalve corresponding to the waste liquid flow channel, the waste liquid flow channel is connected to the paired flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel;

[0027] When the detection module does not identify a single first target object, the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel;

[0028] And / or, when the detection module does not identify a single second target object, the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

[0029] In other embodiments of the present invention, the detection module includes a camera and a controller, and the controller is configured to control the camera to capture images;

[0030] wherein the image includes at least a first image of a first portion of the first flow channel communicating with the paired flow channel, and the controller is further configured to identify the single first target object based on the first image;

[0031] And / or, the image includes at least a second image of a second portion of the second flow channel communicating with the mating flow channel, and the controller is further configured to identify the single second target object based on the second image.

[0032] In other embodiments of the present invention, the image includes at least a third image of the paired flow channel, and the controller is configured to identify whether the single first object and / or the single second object exists in the paired flow channel based on the third image.

[0033] In other embodiments of the present invention, the detection module includes a first light source, a first light detection device, and a controller, wherein the controller is configured to control the first light source to emit a first detection light toward the first flow channel, wherein the first detection light is capable of irradiating the single first target and stimulating a first fluorescence, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target;

[0034] And / or, the detection module 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 a second detection light to the second flow channel, the second detection light can excite a second fluorescence after irradiating the single second target object, and when the second light detection device detects the second fluorescence, the controller identifies the single second target object.

[0035] In other embodiments of the present invention, the detection module includes a first detection electrode and a controller, the first detection electrode extending into the first flow channel, and the controller configured to identify the single first target based on a signal detected by the first detection electrode;

[0036] And / or, the detection module includes a second detection electrode and a controller, the second detection electrode extends into the second flow channel, and the controller is configured to identify the single second target based on a signal detected by the second detection electrode.

[0037] In other embodiments of the present invention, when the detection module identifies the single first target object, the first microvalve switches from an open state to a closed state after a set delay time, so that the single first target object enters the paired flow channel from the first flow channel;

[0038] And / or, when the detection module identifies the single second target object, the second microvalve switches from the open state to the closed state after a set delay, so that the single second target object enters the paired flow channel from the second flow channel.

[0039] In other embodiments of the present invention, the microfluidic system further includes an injection channel, the injection channel being connected to the oil channel, the connection portion between the paired channel and the oil channel being defined as a first connection portion, the connection portion between the injection channel and the oil channel being defined as a second connection portion, and the second connection portion being located downstream of the first connection portion along the flow direction of the oil in the oil channel;

[0040] The microfluidic system further includes a fusion electrode, which is used to apply an electric field to the second communication portion to cause the liquid in the injection channel to merge into the liquid droplet flowing through the second communication portion.

[0041] In other embodiments of the present invention, the microfluidic system has a processing area, and the first flow channel, the second flow channel, the oil flow channel, the buffer flow channel, the pairing flow channel, and the injection flow channel are all located in the processing area;

[0042] The fusion electrode includes a first electrode and a second electrode, and the first electrode is arranged around the processing area.

[0043] In other embodiments of the present invention, both ends of the first electrode are arranged in parallel with the second electrode, and the second electrode is arranged between the two ends of the first electrode.

[0044] In other embodiments of the present invention, the microfluidic system further includes an oil microvalve provided corresponding to the oil flow channel, and the oil microvalve is used to control the on-off of the oil flow channel.

[0045] In other embodiments of the present invention, the microfluidic system further includes a first microvalve control flow channel, the first microvalve includes a diaphragm disposed between the first flow channel and the first microvalve control flow channel, the diaphragm being capable of being driven to protrude toward the first flow channel to be in a closed state;

[0046] Wherein, the inner wall of the first flow channel is an arc-shaped inner wall.

[0047] In other embodiments of the present invention, the microfluidic system includes a microfluidic chip, and the microfluidic chip includes a base layer, a control layer, and a flow channel layer stacked in sequence;

[0048] The flow channel layer comprises the first flow channel, the second flow channel, the oil flow channel, the buffer flow channel and the paired flow channel;

[0049] The control layer includes the paired microvalve, the first microvalve, the second microvalve, and the buffer microvalve.

[0050] In other embodiments of the present invention, the first target is a cell, and the second target is a microsphere.

[0051] In other embodiments of the present invention, the microspheres are magnetic microspheres.

[0052] In other embodiments of the present invention, the microspheres are fluorescent magnetic microspheres.

[0053] In other embodiments of the present invention, the first target is a first cell, and the second target is a second cell.

[0054] According to a second embodiment of the present invention, a microfluidic system for target pairing includes a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, and a pairing flow channel. The pairing flow channel is connected to the oil flow channel, the first flow channel and the second flow channel are both connected to the pairing flow channel, the buffer flow channel is connected to the first flow channel and the second flow channel, respectively. The first flow channel has a first portion connected to the pairing flow channel, and the second flow channel has a second portion connected to the pairing flow channel.

[0055] The microfluidic system further includes a first microvalve provided corresponding to the first flow channel, a second microvalve provided corresponding to the second flow channel, and a buffer microvalve provided corresponding to the buffer flow channel, wherein the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel;

[0056] Among them, when there is a single first target object in the first part and a single second target object in the second part, the first microvalve and the second microvalve are in a closed state, and the buffer microvalve is in an open state, so that the buffer solution in the buffer flow channel sends the single first target object in the first part and the single second target object in the second part through the matching flow channel into the oil in the oil flow channel to form droplets.

[0057] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve corresponding to the waste liquid flow channel, and a droplet microvalve corresponding to the droplet flow channel, wherein the waste liquid flow channel and the droplet flow channel are respectively connected to the oil flow channel, the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel;

[0058] When the first microvalve and the waste liquid microvalve are in an open state and the droplet microvalve is in a closed state, the liquid in the first flow channel can flow out through the paired flow channel, the oil flow channel and the waste liquid flow channel;

[0059] And / or, when the second microvalve and the waste liquid microvalve are in the open state, and the droplet microvalve is in the closed state, the liquid in the second flow channel can flow out through the matching flow channel, the oil flow channel and the waste liquid flow channel.

[0060] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve corresponding to the waste liquid flow channel, and a droplet microvalve corresponding to the droplet flow channel, wherein the waste liquid flow channel and the droplet flow channel are respectively connected to the oil flow channel, the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel;

[0061] When the droplets are formed in the oil in the oil flow channel, the waste liquid microvalve is in a closed state, and the droplet microvalve is in an open state, so that the droplets are discharged through the droplet flow channel.

[0062] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve corresponding to the waste liquid flow channel, and a droplet microvalve corresponding to the droplet flow channel, wherein the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel;

[0063] The paired flow channel is connected to the inlet end of the oil flow channel, and the waste liquid flow channel and the droplet flow channel are both connected to the outlet end of the oil flow channel.

[0064] In other embodiments of the present invention, the microfluidic system further includes a detection module configured to identify a single first target object in the first flow channel, wherein, when the detection module identifies the single first target object, the first microvalve is closed to keep the single first target object in the first portion;

[0065] And / or, the microfluidic system further comprises a detection module, which is configured to identify a single second target object in the second flow channel, wherein, when the detection module identifies the single second target object, the second microvalve is in a closed state to keep the single second target object in the second part.

[0066] The pairing method according to the third embodiment of the present invention includes the following steps:

[0067] identifying a single first target from a first liquid carrying the first target, and stopping the first liquid after identifying the single first target so that the single first target stops in a target area;

[0068] identifying a single second target from a second liquid carrying the second target, and stopping the second liquid after identifying the single second target so that the single second target stops in the target area;

[0069] After the single first target and the single second target both stop in the target area, the single first target and the single second target in the target area are sent into the oil through the third liquid to form droplets.

[0070] In other embodiments of the present invention, the method for identifying a single first target from a first liquid carrying the first target includes the following steps: acquiring an image of a detection area, and identifying the single first target based on image information in the image, wherein the first liquid can enter the target area after passing through the detection area;

[0071] And / or, the method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: acquiring an image of a detection area, and identifying the single second target object based on image information within the image, wherein the second liquid is able to enter the target area after passing through the detection area.

[0072] In other embodiments of the present invention, the method for identifying a single first target from a first liquid carrying the first target includes the following steps: detecting an optical signal within a detection area, and identifying the single first target based on the detected optical signal, wherein the first liquid can enter the target area after passing through the detection area;

[0073] And / or, the method for identifying a single second target from a second liquid carrying the second target includes the following steps: detecting an optical signal within a detection area, and identifying the single second target based on the detection of the optical signal, wherein the second liquid can enter the target area after passing through the detection area.

[0074] In other embodiments of the present invention, the method for identifying a single first target object from a first liquid carrying the first target object includes the following steps: detecting an electrical signal generated by an electrode disposed in a detection region, and identifying the single first target object based on the detected electrical signal, wherein the first liquid can enter the target region after passing through the detection region;

[0075] And / or, the method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: detecting an electrical signal generated by an electrode arranged in a detection area, and identifying the single second target object based on the detection of the electrical signal, wherein the second liquid can enter the target area after passing through the detection area.

[0076] In other embodiments of the present invention, the pairing method further includes the following steps: allowing the droplet containing the single first target object and the single second target object to pass through a fusion region, and applying an electric field to the fusion region to blend a fourth liquid into the droplet.

[0077] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] The present invention will be further described below with reference to the accompanying drawings and examples, in which:

[0079] FIG1 is a schematic diagram of a pairing system in the related art;

[0080] FIG2 is a schematic diagram of a microfluidic system according to a first embodiment of the present invention;

[0081] FIG3 is an enlarged schematic diagram showing the paired flow channels in FIG2 ;

[0082] FIG4 is a schematic diagram of a process for achieving pairing of a first target object with a second target object by a microfluidic system according to the first embodiment of the present invention;

[0083] FIG5 is a schematic diagram of a microfluidic system combined with an electrode detection module in a first embodiment of the present invention;

[0084] FIG6 is a schematic diagram of a microfluidic system combined with an electrofusion module in the first embodiment of the present invention;

[0085] FIG7 is an enlarged schematic diagram showing the electrofusion process in FIG6;

[0086] FIG8 is a schematic diagram of a microvalve in a microfluidic system in an open state and a closed state according to the first embodiment of the present invention;

[0087] FIG9 is an exploded schematic diagram of the microfluidic chip in the first embodiment of the present invention;

[0088] FIG10 is a schematic diagram of a microfluidic system according to a second embodiment of the present invention.

[0089] Reference numerals:

[0090] First flow channel 1, second flow channel 2, oil flow channel 3, waste liquid flow channel 4, sample flow channel 5;

[0091] Microfluidic chip 100, base layer 110, control layer 120, first microvalve 121, diaphragm 1211, second microvalve 122, oil microvalve 123, buffer microvalve 124, waste liquid microvalve 125, paired microvalve 126, channel layer 130, first channel 131, first portion 1311, second channel 132, second portion 1321, oil channel 133, first connecting portion 1331, second connecting portion 1332, buffer channel 134, fourth portion 1341, waste liquid channel 135, third portion 1351, paired channel 136, injection channel 137, first microvalve control channel 138, first injection port 1391, second injection port 1392, third injection port 1393;

[0092] First detection light 210 , second detection light 220 , first detection electrode 230 , second detection electrode 240 ;

[0093] Fusion electrode 300, first electrode 310, second electrode 320;

[0094] A single first target object A;

[0095] a single second target object B;

[0096] Droplet C. DETAILED DESCRIPTION

[0097] The following describes embodiments of the present invention in detail. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended only to explain the present invention and are not to be construed as limiting the present invention.

[0098] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, they cannot be understood as limitations on the present invention.

[0099] In the description of the present invention, "several" means more than one, "plurality" means more than two, "greater than," "less than," and "exceed" are understood to exclude the number itself, while "above," "below," and "within" are understood to include the number itself. The use of "first" and "second" in the description is solely for the purpose of distinguishing technical features and should not be construed as indicating or implying relative importance, implicitly specifying the number of the indicated technical features, or implicitly specifying the order of the indicated technical features.

[0100] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, and connecting should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention based on the specific content of the technical solution.

[0101] In the description of the present invention, reference to terms such as "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the exemplary expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0102] The first embodiment of the present invention provides a microfluidic system for target pairing. Referring to Figures 2 to 4, the system includes a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134, and a pairing flow channel 136. The first flow channel 131 is used to allow a first liquid containing a first target to pass through, the second flow channel 132 is used to allow a second liquid containing a second target to pass through, the buffer flow channel 134 is used to allow a buffer to pass through, the oil flow channel 133 is used to allow an oil that is incompatible with the first liquid, the second liquid, and the buffer to pass through, and the pairing flow channel 136 is used to allow a single first target and a single second target to reside. The pairing flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132, and the buffer flow channel 134 are all connected to the pairing flow channel 136. In some further embodiments, the microfluidic system further includes a waste liquid flow channel 135, which is used to discharge the first liquid and the second liquid. In this embodiment, the first target is a cell and the second target is a microsphere. Those skilled in the art will understand that the first target can be a cell and the second target can also be a cell.

[0103] The microfluidic system of this embodiment also includes a plurality of microvalves, specifically including a paired microvalve 126 arranged corresponding to the paired flow channel 136, a first microvalve 121 arranged corresponding to the first flow channel 131, a second microvalve 122 arranged corresponding to the second flow channel 132, and a buffer microvalve 124 arranged corresponding to the buffer flow channel 134, wherein the paired microvalve 126 is used to control the on-off of the paired flow channel 136, the first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer microvalve 124 is used to control the on-off of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the so-called on-off of the first microvalve 121 controller of the first flow channel 131 means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in an open state, the first flow channel 131 is in a unobstructed state, and the first liquid can flow in the first flow channel 131. When the first microvalve 121 is in a closed state, the first flow channel 131 is in a cut-off state, and the first liquid cannot flow in the first flow channel 131.

[0104] In this embodiment, referring to Figure 4, when there is a single first target A and a single second target B in the pairing flow channel 136, the first microvalve 121 and the second microvalve 122 are in a closed state (the microvalves are filled in black to indicate that they are in a closed state), and the pairing microvalve 126 and the buffer microvalve 124 are in an open state (the microvalves are filled in gray to indicate that they are in an open state). At this time, the buffer solution in the buffer flow channel 134 can deliver the single first target A and the single second target B in the pairing flow channel 136 into the oil in the oil flow channel 133 to form droplets C.

[0105] As can be seen from the above, this embodiment is provided with a separate pairing flow channel 136 for temporarily storing a single first target A and a single second target B, and is provided with a separate buffer flow channel 134, which pushes the single first target A and the single second target B into the oil through the buffer, without the need to push the single first target A and the single second target B through the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be maintained in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0106] Based on the first embodiment, with reference to Figures 2 and 3, in some embodiments of the present invention, the microfluidic system further includes a waste liquid channel 135, which is used to discharge the first liquid and the second liquid, and the waste liquid channel 135 is connected to the matching channel 136. In addition, the microfluidic system further includes a waste liquid microvalve 125 provided corresponding to the waste liquid channel 135, and the waste liquid microvalve 125 is used to control the on-off of the waste liquid channel 135. When the matching microvalve 126 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, the first liquid in the first channel 131 can flow out through the matching channel 136 and the waste liquid channel 135. It should be noted that the first target object will follow the flow of the first liquid and gradually approach and reach the paired flow channel 136. When the first target object has not yet reached the paired flow channel 136, the first flow channel 131 will continue to discharge the first liquid, which needs to be discharged as waste liquid. In this embodiment, after the first liquid is discharged from the first flow channel 131, it will first enter the paired flow channel 136 and then enter the waste liquid flow channel 135 for discharge. In other words, the first liquid of this embodiment will not pass through the oil flow channel 133 when being discharged. Compared with the solution shown in Figure 1, this solution also has the following advantages:

[0107] 1. In the scheme shown in Figure 1, since the waste liquid needs to pass through the oil flow channel 3 when it is discharged, it will inevitably take away the oil in the oil flow channel 3, resulting in a waste of oil. In this embodiment, the first liquid and the second liquid will not pass through the oil flow channel 133 when they are discharged, so they will not take away the oil in the oil flow channel 133, which can reduce the amount of oil used.

[0108] 2. In the scheme shown in Figure 1, since the waste liquid needs to be discharged through the oil flow channel 3, the oil flow channel 3 needs to be closed during waste discharge. After the pairing is completed, the first flow channel 1, the second flow channel 2, and the oil flow channel 3 need to be opened synchronously. Otherwise, the oil flow channel 3 will not provide oil in time and droplets cannot be formed. Therefore, the control requirements for the microvalves corresponding to the first flow channel 1, the second flow channel 2, and the oil flow channel 3 in the scheme shown in Figure 1 are extremely high, resulting in frequent failures in the encapsulation of the target object, further leading to the loss of the target object. In this embodiment, the first liquid and the second liquid will not pass through the oil flow channel 133 when discharged, so the oil flow channel 133 can be always filled with oil. When the pairing is completed, it is only necessary to open the buffer microvalve 124 and the pairing microvalve 126. Even if the buffer microvalve 124 and the pairing microvalve 126 fail to synchronize, it will not cause encapsulation failure.

[0109] 3. In the scheme shown in Figure 1, after the oil flow channel 3 is closed, some oil will still remain inside. When the waste liquid passes through these residual oil, empty droplets will be generated. The empty droplets will cause mixing with normal droplets. Therefore, the empty droplets and normal droplets need to pass through the microvalve of the waste liquid flow channel 4 and the microvalve of the sample flow channel 5 to assist in entering different flow channels. However, this also places extremely high demands on the control of the two microvalves, otherwise it will cause losses. For example, after the droplets are formed, if the microvalve of the waste liquid flow channel 4 fails to close in time and the microvalve of the sample flow channel 5 fails to open in time, the successfully encapsulated droplets will also enter the waste liquid flow channel 4. In this embodiment, the first liquid and the second liquid will not pass through the oil flow channel 133 when they are discharged. The encapsulated droplet C can reach the subsequent storage location along with the flow of oil in the oil flow channel 133, without involving the selection of subsequent flow channels. On the one hand, it reduces the control difficulty, and on the other hand, it avoids the loss of target objects caused by these reasons.

[0110] 4. As previously mentioned, the scheme shown in FIG1 generates a large number of empty droplets, which require valve switching for sorting, significantly affecting processing speed. Compared to the scheme in FIG1 , the microfluidic chip structure of this embodiment avoids the generation of a large number of empty droplets and does not require sorting of empty droplets and sample droplets, thereby improving pairing efficiency. For example, 5 to 10 droplets can be generated per second, or 18,000 to 36,000 droplets per hour. In addition, the microfluidic chip structure of this embodiment can significantly reduce the difficulty of controlling the microvalve.

[0111] In some embodiments, the microfluidic system further comprises a power element such as a pump for driving the flow of the buffer. In some specific embodiments, the microfluidic system comprises a high-speed pump that can achieve high-speed flow and stop of the buffer, thereby adapting to high-speed pairing.

[0112] Based on the first embodiment, with reference to Figures 2 and 3, in some embodiments of the present invention, the waste liquid channel 135 is directly connected to the paired channel 136. The microfluidic system further includes a waste liquid microvalve 125 corresponding to the waste liquid channel 135. The waste liquid microvalve 125 is used to control the on / off state of the waste liquid channel 135. When the paired microvalve 126 is closed and the second microvalve 122 and the waste liquid microvalve 125 are open, the liquid in the second channel 132 can flow out through the paired channel 136 and the waste liquid channel 135. The discharge process of the second liquid can be understood with reference to the discharge process of the first liquid and will not be described in detail here.

[0113] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to Figures 2 and 3, in some embodiments of the present invention, the first flow channel 131, the second flow channel 132, the buffer flow channel 134, and the waste liquid flow channel 135 are all located on the side of the matching microvalve 126 away from the oil flow channel 133. In this way, before the matching is completed, the first liquid, the second liquid, etc. can be prevented from entering the oil flow channel 133. Specifically in the illustrated embodiment, the oil flow channel 133 is distributed in the horizontal direction, and the matching flow channel 136 is distributed in the vertical direction and the lower end is connected to the oil flow channel 133. Then, the matching microvalve 126 is approximately located at the lower end of the matching flow channel 136, and the first flow channel 131, the second flow channel 132, the buffer flow channel 134, and the waste liquid flow channel 135 are all located on the upper side of the matching microvalve 126.

[0114] Combined with the above structure, the control of each microvalve is described:

[0115] 1. Pairing process

[0116] The buffer microvalve 124 and the paired microvalve 126 are closed, the first microvalve 121, the second microvalve 122, and the waste liquid microvalve 125 are opened, and the first liquid and the second liquid are discharged through the paired flow channel 136 and the waste liquid flow channel 135. When a single first target is identified, the first microvalve 121 is closed, and the single first target stops in the paired flow channel 136 (for example, b in Figure 4). When a single second target is identified, the second microvalve 122 is closed, and the single second target stops in the paired flow channel 136 (for example, c in Figure 4). When both the single first target and the single second target stop in the paired flow channel 136, the waste liquid microvalve 125 is closed (for example, c in Figure 4).

[0117] 2. Packaging process

[0118] When the first microvalve 121, the second microvalve 122, and the waste liquid microvalve 125 are closed, the buffer microvalve 124 and the matching microvalve 126 are opened, and the buffer sends the single first target object and the single second target object in the matching flow channel 136 into the oil in the oil flow channel 133 to form droplets (for example, d in Figure 4).

[0119] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to Figure 3, in some embodiments of the present invention, along the extension direction of the matching flow channel 136, the waste liquid flow channel 135 is located between the first flow channel 131 and the second flow channel 132. In this way, when the first liquid is discharged, it will not drive the single second target object B that has been stationary. Similarly, when the second liquid is discharged, it will not drive the single second target object A that has been stationary. The discharge of the first liquid and the second liquid can be carried out synchronously.

[0120] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to FIG3 , in some embodiments of the present invention, the first flow channel 131 and the second flow channel 132 are located on the same side of the matching flow channel 136, and the waste liquid flow channel 135 is located on the other side of the matching flow channel 136. Specifically, in the embodiment shown in FIG3 , the first flow channel 131 and the second flow channel 132 are located on the left side of the matching flow channel 136, and the waste liquid flow channel 135 is located on the right side of the matching flow channel 136. In this way, the first liquid and the second liquid can flow in substantially the same direction, facilitating the discharge of the waste liquid.

[0121] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to Figure 3, in the first flow channel 131 in the embodiment of the present invention, at least the first portion 1311 that is connected to the matching flow channel 136 is arranged to intersect with the matching flow channel 136. Specifically, in the embodiment shown in Figure 3, the first portion 1311 is perpendicular to the matching flow channel 136.

[0122] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to Figure 3, in the second flow channel 132 in the embodiment of the present invention, at least the second portion 1321 connected to the matching flow channel 136 is arranged to intersect with the matching flow channel 136. Specifically, in the embodiment shown in Figure 3, the second portion 1321 is perpendicular to the matching flow channel 136.

[0123] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136 , referring to FIG3 , at least the third portion 1351 of the waste liquid flow channel 135 that is connected to the matching flow channel 136 is arranged to intersect with the matching flow channel 136 . Specifically, in the embodiment shown in FIG3 , the third portion 1351 is perpendicular to the matching flow channel 136 .

[0124] When the waste liquid flow channel 135 is directly connected to the matching flow channel 136, referring to FIG3 , at least the fourth portion 1341 of the buffer flow channel 134 that is connected to the matching flow channel 136 is coaxially arranged with the matching flow channel 136. In this manner, the buffer can enter the matching flow channel 136 in the same direction and drive the single first target A and the single second target B into the oil. It should be noted that in this embodiment, the buffer flow channel 134 and the matching flow channel 136 can be two parts of a single flow channel. For example, FIG3 shows the lower portion of the vertical flow channel as the matching flow channel 136, and the upper portion as the buffer flow channel 134. For ease of reading, the dashed-line box in the figure roughly indicates the range of the matching flow channel 136. However, the dashed-line box should not be construed as a specific limitation on the shape or length of the matching flow channel 136.

[0125] It is understandable that the above embodiments may be combined, that is, the first portion 1311 , the second portion 1321 and the third portion 1351 are all arranged to intersect with the matching flow channel 136 , and the fourth portion 1341 is coaxially arranged with the matching flow channel 136 .

[0126] Based on the first embodiment, the microfluidic system of some embodiments of the present invention further includes a detection module, which is configured to identify a single first target object A in the first flow channel 131. When the detection module identifies the single first target object A, both the first microvalve 121 and the paired microvalve 126 are closed to retain the single first target object A in the paired flow channel 136. It should be noted that in this embodiment, the first microvalve 121 being in the closed state specifically refers to switching from an open state to a closed state, and the paired microvalve 126 being in the closed state specifically refers to remaining in the closed state.

[0127] In other embodiments, the detection module is configured to identify a single second object B in the second flow channel 132. When the detection module identifies the single second object B, both the second microvalve 122 and the paired microvalve 126 are closed to retain the single second object B in the paired flow channel 136. It should be noted that, in this embodiment, the second microvalve 122 being in the closed state specifically refers to switching from an open state to a closed state, and the paired microvalve 126 being in the closed state specifically refers to remaining in the closed state.

[0128] When a single first target object A is identified by the detection module, in some embodiments of the present invention, the microfluidic system further includes a waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and the waste liquid microvalve 125 is used to control the on-off of the waste liquid flow channel 135. When the detection module does not identify a single first target object A, the paired microvalve 126 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the paired flow channel 136 and the waste liquid flow channel 135. It should be noted that, in this embodiment, the paired microvalve 126 being in a closed state specifically refers to being maintained in a closed state, and the first microvalve 121 and the waste liquid microvalve 125 being in an open state specifically refers to being maintained in an open state.

[0129] When a single second target object B is identified by the detection module, in some embodiments of the present invention, when the detection module does not identify a single second target object B, the paired microvalve 126 is closed and the second microvalve 122 and the waste liquid microvalve 125 are opened, so that the liquid in the second flow channel 132 can flow out through the paired flow channel 136 and the waste liquid flow channel 135. It should be noted that in this embodiment, the paired microvalve 126 being closed specifically means being maintained in the closed state, and the second microvalve 122 and the waste liquid microvalve 125 being open specifically means being maintained in the open state.

[0130] When a single first target object A is identified by the detection module, in some embodiments of the present invention, the detection module is specifically a visual detection module, which includes a camera and a controller, wherein the controller is configured to control the camera to capture an image. In this embodiment, the image captured by the camera includes at least a first image of the first portion 1311 connecting the first flow channel 131 and the paired flow channel 136. After the camera captures the image, the controller is further configured to identify the single first target object A based on the first image. In other words, the single first target object A is identified before entering the paired flow channel 136. It should be noted that the microspheres in this embodiment can be magnetic microspheres, which can be attracted by a magnetic member for recovery.

[0131] In other embodiments, the image captured by the camera includes at least a second image of the second portion 1321 of the second flow channel 132 connected to the pairing flow channel 136, and the controller is further configured to identify a single second target object B based on the second image. In other words, the single second target object B has completed the identification operation before entering the pairing flow channel 136.

[0132] In the above process, after the image captured by the camera is transmitted to the controller, the controller detects the target within the detection area (for example, an area with a length and width of 200 pixels respectively), and classifies the cropped target image through the model trained by the convolutional neural network. The controller makes a judgment and controls the corresponding microvalve based on the classification output.

[0133] When the detection module identifies a single first target object A through an image, in some embodiments of the present invention, the image captured by the camera also includes at least a third image of the pairing flow channel 136, and the controller is configured to identify whether the single first target object A exists in the pairing flow channel 136 based on the third image. In other words, in this embodiment, the image captured by the camera can also be used to verify whether the single first target object A has entered the pairing flow channel 136.

[0134] In other embodiments, the image captured by the camera also includes at least a third image of the pairing channel 136, and the controller is configured to identify whether a single second target object B exists in the pairing channel 136 based on the third image. In other words, in this embodiment, the image captured by the camera can also be used to verify whether the single second target object B has entered the pairing channel 136.

[0135] It should be noted that the above embodiments can be combined. For example, the image captured by the camera includes the aforementioned first image, second image and third image. In this way, the controller can implement combined operations through the same image, such as simultaneously identifying a single first target A and a single first target B, or identifying a single first target A and determining whether a single second target B has reached the paired flow channel 136, or identifying a single first target B and determining whether a single first target A has reached the paired flow channel 136, or determining whether a single first target A and a single second target B have reached the paired flow channel 136.

[0136] When identifying a single first target A through the detection module, in some embodiments of the present invention, 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 210 into the first flow channel 131. The first detection light 210 can excite first fluorescence after irradiating the single first target A. The first light detection device can receive the first fluorescence excited by the single first target A. For example, the first light source is a laser, and the first light detection device is a photomultiplier tube. After receiving the first fluorescence emitted by the single first target A, the photomultiplier tube can convert the optical signal into an electrical signal and transmit it to the controller. It should be noted that the microspheres in this embodiment can be fluorescent magnetic microspheres dyed with a fluorescent substance, which can emit fluorescence when excited by an external light source.

[0137] 4 , the first light source projects a first detection light 210 toward a set position of the first flow channel 131 . When no cells reach the set position, the first light detection device does not receive a light signal. When a cell reaches the set position, the cell is excited by the first detection light 210 and generates fluorescence. When the first light detection device detects the first fluorescence, the detection device identifies a single first target object A.

[0138] When a single second target object B is identified through the detection module, in some embodiments of the present invention, the detection module is specifically a fluorescence detection module, a second light source, a second light detection device and a controller, and the controller is configured to control the second light source to emit a second detection light 220 to the second flow channel 132. The second detection light 220 can excite the 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.

[0139] The first target A / second target B identification scheme based on fluorescence is described in conjunction with FIG4 :

[0140] 1. Identification of the first target A

[0141] The first microvalve 121 is in an open state, and the first liquid continues to flow through the first detection position illuminated by the first detection light 210. When a single first target object A passes through the first detection position along with the first liquid, it is excited by the first detection light 210 to generate a first fluorescence. The first fluorescence is received by the first light detection device and an electrical signal is generated. The controller identifies the single first target object A based on the electrical signal, and then controls the first microvalve 121 to switch to a closed state, so that the single first target object A stops in the paired flow channel 136.

[0142] 2. Second target identification

[0143] The second microvalve 122 is in an open state, and the second liquid continues to flow through the second detection position illuminated by the second detection light 220. When a single second target object B passes through the second detection position along with the second liquid, it is excited by the second detection light 220 to generate a second fluorescence. The second fluorescence is received by the second light detection device and an electrical signal is generated. The controller recognizes the single second target object B based on the electrical signal and then controls the second microvalve 122 to switch to a closed state, so that the single second target object B stops in the paired flow channel 136.

[0144] It should be noted that the first light source and the second light source can be lasers with different wavelengths.

[0145] When a single first target A is identified by a detection module, in some embodiments of the present invention, the detection module is specifically an electrode detection module. Referring to FIG5 , the detection module includes a first detection electrode 230 and a controller. The first detection electrode 230 extends into the first flow channel 131. When the single first target A passes through the first detection electrode 230, the first detection electrode 230 generates a corresponding signal. The controller is configured to identify the single first target A based on the signal detected by the first detection electrode 230. Specifically, the first detection electrode 230 includes a positive electrode and a negative electrode, which are arranged in parallel. When the microfluidic system includes the microfluidic chip 100, the first detection electrode 230 can be a metal layer disposed between the control layer 120 and the flow channel layer 130 of the microfluidic chip 100. Furthermore, in this embodiment, the signal detected by the first detection electrode 230 can be a change in amplitude and phase difference. It should be noted that the microspheres in this embodiment can be magnetic microspheres that can be attracted by a magnetic member for recovery.

[0146] When a single second target object B is identified by the detection module, in some embodiments of the present invention, the detection module is specifically an electrode detection module, as shown in FIG5 , which includes a second detection electrode 240 and a controller. The second detection electrode 240 extends into the second flow channel 132 , and the controller is configured to identify the single second target object B based on the signal detected by the second detection electrode 240 . The second detection electrode 240 can be understood with reference to the first detection electrode 230 .

[0147] When a single first target object A is identified by the detection module, in some embodiments of the present invention, after the detection module identifies the single first target object A, the first microvalve 121 switches from an open state to a closed state after a set delay, so that the single first target object A can enter the paired flow channel 136 from the first flow channel 131. Referring to Figures 4 and 5, the identification position for identifying the single first target object A is a certain distance away from the paired flow channel 136. In this embodiment, the first microvalve 121 is closed with a delay to ensure that the single first target object A can enter the paired flow channel 136. It should be noted that the set delay time can be determined based on the distance between the identification position and the paired flow channel 136 and the flow rate of the first liquid.

[0148] When a single second object B is identified by the detection module, in some embodiments of the present invention, after the detection module identifies the single second object B, the second microvalve 122 switches from an open state to a closed state after a set delay, so that the single second object B can enter the paired flow channel 136 from the second flow channel 132. Referring to Figures 4 and 5, the identification position for identifying the single second object B is a certain distance away from the paired flow channel 136. In this embodiment, the second microvalve 122 is closed with a delay to ensure that the single second object B can enter the paired flow channel 136. It should be noted that the set delay time can be determined based on the distance between the identification position and the paired flow channel 136 and the flow rate of the second liquid.

[0149] Based on the first embodiment, referring to FIG6 and FIG7 , in some embodiments of the present invention, the microfluidic system further includes a liquid injection system, which is used to inject liquid into the droplet C, for example, inject reverse transcription liquid into the droplet C. Specifically, the microfluidic system further includes an injection channel 137 , which is connected to the oil flow channel 133 . The connection point between the paired flow channel 136 and the oil flow channel 133 is defined as a first connection point 1331 , and the connection point between the injection channel 137 and the oil flow channel 133 is defined as a second connection point 1332 . The second connection point 1332 is located downstream of the first connection point 1331 along the flow direction of the oil in the oil flow channel 133 .

[0150] The microfluidic system also includes a fusion electrode 300, which is used to apply an electric field to the second connecting portion 1332. When the droplet C passes through the second connecting portion 1332, the liquid in the injection channel 137 is fused into the droplet C under the action of the electric field. The liquid in the injection channel 137 is also insoluble in the oil, and the pressure in the injection channel 137 is relatively low, causing the liquid in the injection channel 137 to slightly protrude into the oil channel 133. As a result, when the droplet C passes through the second connecting portion 1332, it can contact the liquid in the injection channel 137, thereby facilitating fusion of the two.

[0151] When the microfluidic system also includes an injection system, as shown in Figures 6 and 7 , in some embodiments of the present invention, the flow channel layer 130 includes a processing area, within which the first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste flow channel 135, the paired flow channel 136, and the injection flow channel 137 are all located. It should be noted that the processing area is intended to aid understanding and does not necessarily represent a clearly defined and identifiable area within the microfluidic system.

[0152] In this embodiment, the fusion electrode 300 includes a first electrode 310 and a second electrode 320, wherein the first electrode 310 is arranged around the processing area to achieve a better electrofusion effect. In some specific embodiments, when the microfluidic system includes a microfluidic chip 100, an electrode channel is provided on the flow channel layer 130 of the microfluidic chip 100, and a metal rod is inserted into the electrode channel. When the metal rod is heated, the metal rod melts and fills the electrode channel. After cooling, the first electrode 310 and the second electrode 320 are formed. In some embodiments, the electrode channel has an electrode injection port to facilitate the injection of the metal rod. Taking FIG6 as an example, the electrode injection port includes a first injection port 1391 and a second injection port 1392 at both ends of the first electrode channel, and a third injection port 1393 at one end of the second electrode channel. It should be noted that in this embodiment, the length of the first electrode channel is relatively long. When the metal liquid fills the electrode channel, the other injection port can serve as an exhaust port, thereby facilitating the metal liquid to fill the entire electrode channel.

[0153] When the fusion electrode 300 includes a first electrode 310 and a second electrode 320, and the first electrode 310 surrounds the processing area, referring to Figure 7, in some embodiments of the present invention, the two ends of the first electrode 310 are arranged in parallel with the second electrode 320, and the second electrode 320 is arranged between the two ends of the first electrode 310 to achieve a better electrical fusion effect.

[0154] Based on the first embodiment, referring to FIG2 , in some embodiments of the present invention, the microfluidic chip 100 further includes an oil microvalve 123 disposed corresponding to the oil flow channel 133. The oil microvalve 123 is used to control the opening and closing of the oil flow channel 133. When the oil microvalve 123 is opened, the oil in the oil flow channel 133 flows, driving the droplet C downstream. Specifically, in the illustrated embodiment, the oil microvalve 123 is located upstream of the first connecting portion 1331 along the flow direction of the oil in the oil flow channel 133.

[0155] On the basis of the first embodiment, in some embodiments of the present invention, the microfluidic system further includes a first microvalve control channel 138. Referring to Figure 8, the first microvalve 121 includes a diaphragm 1211 arranged between the first channel 131 and the first microvalve control channel 138. When the first microvalve 121 is in an open state as shown in a in Figure 8, the diaphragm 1211 is in a horizontal state, and the first liquid can flow in the first channel 131; when the diaphragm 1211 is driven to protrude toward the first channel 131 to be in a closed state as shown in b in Figure 8, the diaphragm 1211 is close to the inner wall of the first channel 131 to cut off the first channel 131, and the first liquid cannot flow in the first channel 131.

[0156] In this embodiment, the inner wall of the first flow channel 131 is an arc-shaped inner wall, which is convenient for adhering to the diaphragm 1211 protruding toward the first flow channel 131, thereby ensuring a cut-off effect.

[0157] It should be noted that, in addition to the aforementioned first microvalve control flow channel 138, the microfluidic system also includes microvalve control flow channels corresponding to the second microvalve 122, the oil microvalve 123, the buffer microvalve 124, the waste liquid microvalve 125, and the matching microvalve 126. Accordingly, the second microvalve 122, the oil microvalve 123, the buffer microvalve 124, the waste liquid microvalve 125, and the matching microvalve 126 all include diaphragms. Their specific settings and control methods can be understood with reference to the first microvalve control flow channel 138 and will not be described in detail here.

[0158] It should also be noted that the power for driving the diaphragm 1211 to bulge may be air pressure. In this embodiment, the first microvalve control channel 138 is filled with liquid, and an external air source drives the liquid in the first microvalve control channel 138 to flow, thereby pushing the diaphragm 1211 to bulge or reset. Compared with the direct air pressure driving method, since the liquid is difficult to compress, this method can achieve a rapid response of the diaphragm 1211, thereby adapting to high-speed pairing.

[0159] On the basis of the first embodiment, referring to Figure 9, in some embodiments of the present invention, the microfluidic system includes a microfluidic chip 100, and the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 stacked in sequence. 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).

[0160] The flow channel layer 130 includes the aforementioned first flow channel 131, second flow channel 132, oil flow channel 133, buffer flow channel 134, waste flow channel 135, and paired flow channel 136. The control layer 120 includes the aforementioned paired microvalve 126, first microvalve 121, second microvalve 122, and buffer microvalve 124, as well as microvalve control channels corresponding to each microvalve.

[0161] In some embodiments of the present invention, based on the first embodiment, the first target A is a cell, and the second target B is a microsphere. In some embodiments, the microspheres can be further configured as magnetic microspheres, so that RNA released after cell lysis can be adsorbed onto the surface of the microspheres, and the microspheres can be subsequently collected using a magnetic device, thereby collecting the RNA. In some embodiments, the microspheres can be further configured as fluorescent magnetic microspheres, so that they emit fluorescence when stimulated by external light.

[0162] Based on the first embodiment, in some embodiments of the present invention, the first target A is a first cell, and the second target B is a second cell, which are used to study the interaction effect between cells.

[0163] The second embodiment of the present invention proposes a microfluidic system for target pairing. The difference between the second embodiment and the first embodiment is that the first target A and the second target B of the microfluidic system in the first embodiment stop in the pairing channel 136, while the first target A and the second target B in this embodiment stop in the first channel 131 and the second channel 132.

[0164] 10 , the microfluidic system includes a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134, and a matching flow channel 136. The first flow channel 131 is used to allow a first liquid containing a first target to pass through, the second flow channel 132 is used to allow a second liquid containing a second target to pass through, the buffer flow channel 134 is used to allow a buffer to pass through, and the oil flow channel 133 is used to allow an oil that is incompatible with the first liquid, the second liquid, and the buffer to pass through. The matching flow channel 136 is connected to the oil flow channel 133, the first flow channel 131 and the second flow channel 132 are both connected to the matching flow channel 136, the buffer flow channel 134 is connected to the first flow channel 131 and the second flow channel 132, respectively. The first flow channel 131 has a first portion 1311 connected to the matching flow channel, and the second flow channel 132 has a second portion 1321 connected to the matching flow channel. In some further embodiments, the microfluidic system further includes a waste liquid channel 135 , and the waste liquid channel 135 is used to discharge the first liquid and the second liquid.

[0165] The microfluidic system of this embodiment also includes multiple microvalves, specifically including a first microvalve 121 set corresponding to the first flow channel 131, a second microvalve 122 set corresponding to the second flow channel 132, and a buffer microvalve 124 set corresponding to the buffer flow channel 134. The first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer microvalve 124 is used to control the on-off of the buffer flow channel 134. The on-off here can be understood with reference to the first embodiment.

[0166] In this embodiment, referring to Figure 10, when there is a single first target object A in the first part 1311 and a single second target object B in the second part 1321, the first microvalve 121 and the second microvalve 122 are in a closed state, and the buffer microvalve 124 is in an open state, so that the buffer solution in the buffer flow channel 134 first sends the single first target object A in the first part 1311 and the single second target object B in the second part 1321 into the matching flow channel 136, and then sends them together into the oil in the oil flow channel 133 to form droplets.

[0167] As can be seen from the above, this embodiment is provided with a first part 1311 of the first flow channel 131 for temporarily storing a single first target object A, a second part 1321 of the second flow channel 132 is provided for temporarily storing a single second target object B, and a separate buffer flow channel 134 is provided. The buffer solution is used to push the single first target object A and the single second target object B into the oil liquid, and there is no need to push the single first target object A and the single second target object B through the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be maintained in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0168] Based on the second embodiment, referring to FIG10 , in some embodiments of the present invention, the microfluidic system further includes a waste liquid channel 135 and a droplet channel 139. The waste liquid channel 135 is used to discharge excess first and second liquids, and the droplet channel 139 is used to discharge droplets C. Both the waste liquid channel 135 and the droplet channel 139 are connected to the oil channel 133. Furthermore, the microfluidic system further includes a waste liquid microvalve 125 corresponding to the waste liquid channel 135 and a droplet microvalve 127 corresponding to the droplet channel 139. The waste liquid microvalve 125 is used to control the on / off of the waste liquid channel 135, and the droplet microvalve 127 is used to control the on / off of the droplet channel 139. When the first microvalve 121 and the waste liquid microvalve 125 are in the open state, and the droplet microvalve 127 is in the closed state, the first liquid in the first channel 131 can flow out through the paired channel 136, the oil channel 133, and the waste liquid channel 135.

[0169] On the basis of the second embodiment, with reference to FIG10 , in some embodiments of the present invention, the microfluidic system further comprises a waste liquid flow channel 135, a droplet flow channel 139, a waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and a droplet microvalve 127 provided corresponding to the droplet flow channel 139. The waste liquid flow channel 135, the droplet flow channel 139, the waste liquid microvalve 125, and the corresponding droplet flow channel 139 can all be understood with reference to the aforementioned embodiment. When the second microvalve 122 and the waste liquid microvalve 125 are in an open state, and the droplet microvalve 127 is in a closed state, the second liquid in the second flow channel 132 can flow out through the paired flow channel 136, the oil flow channel 133, and the waste liquid flow channel 135. The discharge process of the second liquid can be understood with reference to the first liquid and will not be described in detail here.

[0170] On the basis of the second embodiment, with reference to FIG10 , in some embodiments of the present invention, the waste liquid flow channel 135, the droplet flow channel 139, the waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and the droplet microvalve 127 provided corresponding to the droplet flow channel 139, the waste liquid flow channel 135, the droplet flow channel 139, the waste liquid microvalve 125, and the corresponding droplet flow channel 139 can all be understood with reference to the aforementioned embodiments. In this embodiment, when droplets are formed in the oil in the oil flow channel 133, the waste liquid microvalve 125 is in a closed state, and the droplet microvalve 127 is in an open state, so that the droplets are discharged through the droplet flow channel 139. In combination with the aforementioned embodiments, by switching the waste liquid microvalve 125 and the droplet flow channel 139, the switching between discharging waste liquid and discharging droplets can be achieved.

[0171] Based on the second embodiment, with reference to FIG10 , in some embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel 135, a droplet flow channel 139, a waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and a droplet microvalve 127 provided corresponding to the droplet flow channel 139. The paired flow channel 136 is connected to the inlet end of the oil flow channel 133, and the waste liquid flow channel 135 and the droplet flow channel 139 are connected to the outlet end of the oil flow channel 133. Specifically, in the embodiment shown in FIG10 , the paired flow channel 136 is connected to the upper end of the oil flow channel 133, and the waste liquid flow channel 135 and the droplet flow channel 139 are connected to the lower end of the oil flow channel 133. In addition, the first flow channel 131 and the second flow channel 132 are both connected to the inlet end of the matching flow channel 136, and the end of the buffer flow channel 134 has two branch flow channels, which are respectively connected to the first part 1311 and the second part 1321, and the lengths of the two branch flow channels are equal. In this way, the first target A in the first part 1311 and the second target B in the second part 1321 can be delivered into the matching flow channel 136 roughly synchronously through the buffer solution.

[0172] On the basis of the second embodiment, referring to Figure 10, in some embodiments of the present invention, the microfluidic system further includes an oil microvalve 123 arranged corresponding to the oil flow channel 133. When discharging waste liquid, the oil microvalve 123 is in a closed state, and the waste liquid can enter the waste liquid flow channel 135 through the oil flow channel 133. When encapsulated, the oil microvalve 123 is in an open state, and the oil flow channel 133 will be filled with oil.

[0173] Based on the second embodiment, referring to FIG10 , in some embodiments of the present invention, the microfluidic system further includes a detection module configured to identify a single first target object within the first flow channel 131. When the detection module identifies the single first target object, the first microvalve 121 is closed to retain the single first target object within the first portion 1311. It should be noted that, in this embodiment, the first microvalve 121 being closed specifically refers to switching from an open state to a closed state.

[0174] In other embodiments, the detection module is configured to identify a single second object in the second flow channel 132. When the detection module identifies the single second object, the second microvalve 122 is closed to retain the single second object in the second portion 1321. It should be noted that, in this embodiment, the second microvalve 122 being closed specifically refers to switching from an open state to a closed state.

[0175] When a single first target object A is identified by the detection module, in some embodiments of the present invention, the microfluidic system further includes a waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and the waste liquid microvalve 125 is used to control the on-off state of the waste liquid flow channel 135. Specifically, when the detection module does not identify a single first target object A, the droplet microvalve 127 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the paired flow channel 136, the oil flow channel 133, and the waste liquid flow channel 135. It should be noted that, in this embodiment, the droplet microvalve 127 being in a closed state specifically refers to being maintained in a closed state, and the first microvalve 121 and the waste liquid microvalve 125 being in an open state specifically refers to being maintained in an open state.

[0176] When a single second target object B is identified by the detection module, in some embodiments of the present invention, when the detection module does not identify a single second target object B, the droplet microvalve 127 is in a closed state and the second microvalve 122 and the waste liquid microvalve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the matching flow channel 136, the oil flow channel 133, and the waste liquid flow channel 135. It should be noted that in this embodiment, the droplet microvalve 127 being in a closed state specifically means being maintained in a closed state, and the second microvalve 122 and the waste liquid microvalve 125 being in an open state specifically means being maintained in an open state.

[0177] The different detection methods of the detection module can be understood by referring to the visual detection, fluorescence detection and electrode detection in the first embodiment, and will not be described in detail here.

[0178] The third embodiment of the present invention further proposes a pairing method, comprising the following steps:

[0179] S100 identifies a single first target from the first liquid carrying the first target. After identifying the single first target, the first liquid is stopped so that the single first target stops at a target area. In some embodiments, this step can be performed based on the microfluidic system of the first or second embodiment. That is, the target area in this step can be the paired flow channel 136 of the first embodiment or the first portion 1311 of the second embodiment.

[0180] S200 identifies a single second target from the second liquid carrying the second target. After identifying the single second target, the second liquid is stopped so that the single second target is stopped in a target area. In some embodiments, this step can be performed based on the microfluidic system of the first or second embodiment. That is, the target area in this step can be the paired flow channel 136 of the first embodiment or the second portion 1321 of the second embodiment.

[0181] S300: After the single first target and the single second target both stop in the target area, and the first liquid and the second liquid are in a stopped state, the single first target and the single second target in the target area are sent into the oil via the third liquid to form droplets.

[0182] It should be noted that there is no restriction on the order of step S100 and step S200.

[0183] Based on the third embodiment, in some embodiments of the present invention, a method for identifying a single first target object from a first liquid carrying the first target object includes the following steps: acquiring an image of a detection area, and identifying a single first target object based on image information within the image, wherein the first liquid can enter a target area after passing through the detection area.

[0184] Based on the third embodiment, in some embodiments of the present invention, a method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: acquiring an image of a detection area, and identifying a single second target object based on image information within the image, wherein the second liquid is able to enter the target area after passing through the detection area.

[0185] The aforementioned embodiments can be understood with reference to the visual detection solution in the first embodiment.

[0186] Based on the third embodiment, in some embodiments of the present invention, a method for identifying a single first target object from a first liquid carrying the first target object includes the following steps: detecting an optical signal within a detection area, and identifying the single first target object based on the detected optical signal, wherein the first liquid can enter a target area after passing through the detection area. The optical signal may be fluorescence generated by the first target object when stimulated.

[0187] In some embodiments of the present invention, based on the third embodiment, a method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: detecting an optical signal within a detection area, and identifying the single second target object based on the detected optical signal, wherein the second liquid can enter a target area after passing through the detection area. The optical signal can be fluorescence generated by the second target object when the second liquid is excited.

[0188] The aforementioned embodiments can be understood with reference to the fluorescence detection scheme in the first embodiment.

[0189] Based on the third embodiment, in some embodiments of the present invention, a method for identifying a single first target object from a first liquid carrying the first target object includes the following steps: detecting an electrical signal generated by an electrode arranged in a detection area, and identifying the single first target object based on the detected electrical signal, wherein the first liquid can enter the target area after passing through the detection area.

[0190] Based on the third embodiment, some embodiments of the present invention include the following steps: detecting electrical signals generated by electrodes disposed within a detection region, and identifying the single second target based on the detected electrical signals, wherein the second liquid can enter a target region after passing through the detection region. In this embodiment, the signals detected by the electrodes may be changes in amplitude and phase difference.

[0191] In the aforementioned embodiment, the signal detected by the electrode may be a change in amplitude and phase difference.

[0192] The aforementioned embodiments can be understood with reference to the electrode detection solution in the first embodiment.

[0193] In the aforementioned embodiments, the detection area is located upstream of the target area along the flow direction of the first liquid. For example, when the target area is the pairing channel 136 in the first embodiment, the detection area can be the first portion 1311 in the first channel 131 that is connected to the pairing channel 136. When the target area is the first portion 1311 in the second embodiment, the detection area can be other areas in the first channel 131.

[0194] Along the flow direction of the second liquid, the detection area is located upstream of the target area. For example, when the target area is the pairing channel 136 in the first embodiment, the detection area can be the second part 1321 in the second channel 132 that is connected to the pairing channel 136. When the target area is the second part 1321 in the second embodiment, the detection area can be other areas in the second channel 132.

[0195] In some embodiments of the present invention, based on the third embodiment, the pairing method further includes the following steps: passing a liquid droplet containing a single first target object and a single second target object through a fusion region, and applying an electric field to the fusion region to fuse a fourth liquid into the liquid droplet. In this embodiment, the electric field can be applied via a fusion electrode.

[0196] While the embodiments of the present invention have been described in detail above with reference to the accompanying drawings, the present invention is not limited to the embodiments described above. Various modifications may be made within the scope of knowledge possessed by a person skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof may be combined with one another unless there is a conflict.

Claims

1. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a matching flow channel, the matching flow channel is connected to the oil flow channel, and the first flow channel, the second flow channel and the buffer flow channel are all connected to the matching flow channel; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; Among them, when there is a single first target object and a single second target object in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel can send the single first target object and the single second target object in the paired flow channel into the oil in the oil flow channel to form droplets.

2. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further comprises a waste liquid flow channel and a waste liquid micro valve arranged corresponding to the waste liquid flow channel, the waste liquid flow channel is communicated with the paired flow channel, and the waste liquid micro valve is used to control the on-off of the waste liquid flow channel; Wherein, when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

3. The microfluidic system for target pairing according to claim 2, characterized in that: The first flow channel, the second flow channel, the buffer flow channel and the waste liquid flow channel are all located on a side of the paired microvalve away from the oil flow channel.

4. The microfluidic system for target pairing according to claim 2, characterized in that: The first flow channel and the second flow channel are located on the same side of the matching flow channel, and the waste liquid flow channel is located on the other side of the matching flow channel.

5. The microfluidic system for target pairing according to claim 2, characterized in that: The microfluidic system further comprises at least one of the following solutions: At least a first portion of the first flow channel that is in communication with the paired flow channel is arranged to intersect with the paired flow channel; At least a second portion of the second flow channel that is in communication with the matching flow channel is arranged to intersect with the matching flow channel; At least a third portion of the waste liquid flow channel that is in communication with the matching flow channel is arranged to intersect with the matching flow channel.

6. The microfluidic system for target pairing according to claim 2, characterized in that: At least a fourth portion of the buffer flow channel that is in communication with the matching flow channel is coaxially arranged with the matching flow channel.

7. The microfluidic system for target pairing according to claim 2, characterized in that: Along the extending direction of the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel.

8. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further includes a detection module, wherein the detection module is configured to identify a single first target object in the first flow channel, wherein, when the detection module identifies the single first target object, the first microvalve and the paired microvalve are both in a closed state to keep the single first target object in the paired flow channel; And / or, the microfluidic system also includes a detection module, which is configured to identify a single second target object in the second flow channel, wherein, when the detection module identifies the single second target object, the second microvalve and the matching microvalve are both in a closed state to keep the single second target object in the matching flow channel.

9. The microfluidic system for target pairing according to claim 8, characterized in that: The microfluidic system further comprises a waste liquid flow channel and a waste liquid micro valve arranged corresponding to the waste liquid flow channel, the waste liquid flow channel is communicated with the paired flow channel, and the waste liquid micro valve is used to control the on-off of the waste liquid flow channel; Wherein, when the detection module does not identify a single first target object, the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the detection module does not identify a single second target object, the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

10. The microfluidic system for target pairing according to claim 8, characterized in that: The detection module includes a camera and a controller, and the controller is configured to control the camera to capture images; wherein the image includes at least a first image of a first portion of the first flow channel communicating with the paired flow channel, and the controller is further configured to identify the single first target object based on the first image; And / or, the image includes at least a second image of a second portion of the second flow channel communicating with the mating flow channel, and the controller is further configured to identify the single second target object based on the second image.

11. The microfluidic system for target pairing according to claim 10, characterized in that: The images include at least a third image of the paired flow channel, and the controller is configured to identify whether the single first object and / or the single second object exists in the paired flow channel based on the third image.

12. The microfluidic system for target pairing according to claim 8, characterized in that: The detection module includes a first light source, a first light detection device and a controller, wherein the controller is configured to control the first light source to emit a first detection light to the first flow channel, wherein the first detection light can excite a 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; And / or, the detection module 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 a second detection light to the second flow channel, the second detection light can excite a second fluorescence after irradiating the single second target object, and when the second light detection device detects the second fluorescence, the controller identifies the single second target object.

13. The microfluidic system for target pairing according to claim 8, characterized in that: The detection module includes a first detection electrode and a controller, the first detection electrode extends into the first flow channel, and the controller is configured to identify the single first target object based on a signal detected by the first detection electrode; And / or, the detection module includes a second detection electrode and a controller, the second detection electrode extends into the second flow channel, and the controller is configured to identify the single second target object based on a signal detected by the second detection electrode.

14. The microfluidic system for target pairing according to claim 8, characterized in that: When the detection module identifies the single first target object, the first microvalve switches from an open state to a closed state after a set delay time, so that the single first target object enters the paired flow channel from the first flow channel; And / or, when the detection module identifies the single second target object, the second microvalve switches from an open state to a closed state after a set delay time, so that the single second target object enters the paired flow channel from the second flow channel.

15. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further comprises an injection channel, the injection channel is connected to the oil channel, a connecting portion between the paired channel and the oil channel is defined as a first connecting portion, a connecting portion between the injection channel and the oil channel is defined as a second connecting portion, and the second connecting portion is located downstream of the first connecting portion along the flow direction of the oil in the oil channel; The microfluidic system further includes a fusion electrode, which is used to apply an electric field to the second connecting portion so that the liquid in the injection channel is fused into the droplet flowing through the second connecting portion.

16. The microfluidic system for target pairing according to claim 15, characterized in that: The microfluidic system has a processing area, and the first flow channel, the second flow channel, the oil flow channel, the buffer flow channel, the matching flow channel and the injection flow channel are all located in the processing area; The fusion electrode includes a first electrode and a second electrode, and the first electrode is arranged around the processing area.

17. The microfluidic system for target pairing according to claim 16, characterized in that: Two ends of the first electrode are arranged in parallel with the second electrode, and the second electrode is arranged between the two ends of the first electrode.

18. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further comprises an oil microvalve arranged corresponding to the oil flow channel, and the oil microvalve is used to control the on-off of the oil flow channel.

19. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further comprises a first microvalve control flow channel, the first microvalve comprises a diaphragm disposed between the first flow channel and the first microvalve control flow channel, the diaphragm can be driven to protrude toward the first flow channel to be in a closed state; Wherein, the inner wall of the first flow channel is an arc-shaped inner wall.

20. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system comprises a microfluidic chip, and the microfluidic chip comprises a base layer, a control layer and a flow channel layer which are stacked in sequence; The flow channel layer includes the first flow channel, the second flow channel, the oil flow channel, the buffer flow channel and the matching flow channel; The control layer has the paired microvalve, the first microvalve, the second microvalve, and the buffer microvalve.

21. The microfluidic system for target pairing according to claim 1, characterized in that: The first target is a cell, and the second target is a microsphere.

22. The microfluidic system for target pairing according to claim 21, characterized in that: The microspheres are magnetic microspheres.

23. The microfluidic system for target pairing according to claim 23, characterized in that: The microspheres are fluorescent magnetic microspheres.

24. The microfluidic system for target pairing according to claim 1, characterized in that: The first target is a first cell, and the second target is a second cell.

25. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a matching flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel and the second flow channel are both connected to the matching flow channel, the buffer flow channel is respectively connected to the first flow channel and the second flow channel, the first flow channel has a first part connected to the matching flow channel, and the second flow channel has a second part connected to the matching flow channel; The microfluidic system further comprises a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; When a single first target exists in the first part and a single second target exists in the second part, the first microvalve and the second microvalve are in a closed state, and the buffer microvalve is in an open state, so that the buffer in the buffer flow channel can transfer the single first target in the first part and the second target in the second part. A single second target object is sent into the oil in the oil flow channel through the paired flow channel to form a droplet.

26. The microfluidic system for target pairing according to claim 25, characterized in that: The microfluidic system further comprises a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve arranged corresponding to the waste liquid flow channel, and a droplet microvalve arranged corresponding to the droplet flow channel, the waste liquid flow channel and the droplet flow channel are respectively connected to the oil flow channel, the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel; Wherein, when the first microvalve and the waste liquid microvalve are in an open state, and the droplet microvalve is in a closed state, the liquid in the first flow channel can flow out through the matching flow channel, the oil flow channel and the waste liquid flow channel; And / or, when the second microvalve and the waste liquid microvalve are in an open state, and the droplet microvalve is in a closed state, the liquid in the second flow channel can flow out through the matching flow channel, the oil flow channel and the waste liquid flow channel.

27. The microfluidic system for target pairing according to claim 25, characterized in that: The microfluidic system further comprises a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve arranged corresponding to the waste liquid flow channel, and a droplet microvalve arranged corresponding to the droplet flow channel, the waste liquid flow channel and the droplet flow channel are respectively connected to the oil flow channel, the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel; When the droplets are formed in the oil in the oil flow channel, the waste liquid microvalve is in a closed state, and the droplet microvalve is in an open state, so that the droplets are discharged through the droplet flow channel.

28. The microfluidic system for target pairing according to claim 25, characterized in that: The microfluidic system further comprises a waste liquid flow channel, a droplet flow channel, a waste liquid microvalve arranged corresponding to the waste liquid flow channel, and a droplet microvalve arranged corresponding to the droplet flow channel, wherein the waste liquid microvalve is used to control the on-off of the waste liquid flow channel, and the droplet microvalve is used to control the on-off of the droplet flow channel; Wherein, the paired flow channel is connected to the inlet end of the oil flow channel, and the waste liquid flow channel and the droplet flow channel are both connected to the outlet end of the oil flow channel.

29. The microfluidic system for target pairing according to claim 25, characterized in that: The microfluidic system further includes a detection module, wherein the detection module is configured to identify a single first target object in the first flow channel, wherein, after the detection module identifies the single first target object, the first microvalve is in a closed state to keep the single first target object in the first portion; And / or, the microfluidic system also includes a detection module, which is configured to identify a single second target object in the second flow channel, wherein, when the detection module identifies the single second target object, the second microvalve is in a closed state to keep the single second target object in the second part.

30. A pairing method, characterized in that: The following steps are involved: A single first target is identified from a first liquid carrying the first target, and after identifying the single first target, Stopping the first liquid so that the single first target object stops in the target area; Identifying a single second target from the second liquid carrying the second target, and stopping the second liquid after identifying the single second target so that the single second target stops at the target area; After the single first target object and the single second target object both stop in the target area, the single first target object and the single second target object in the target area are sent into the oil liquid through the third liquid to form droplets.

31. The pairing method according to claim 30, characterized in that: The method for identifying a single first target object from a first liquid carrying the first target object comprises the following steps: acquiring an image of a detection area, identifying the single first target object based on image information in the image, wherein the first liquid can enter the target area after passing through the detection area; And / or, the method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: acquiring an image of a detection area, and identifying the single second target object based on image information in the image, wherein the second liquid can enter the target area after passing through the detection area.

32. The pairing method according to claim 30, characterized in that: The method for identifying a single first target object from a first liquid carrying the first target object comprises the following steps: detecting an optical signal in a detection area, and identifying the single first target object based on the detection of the optical signal, wherein the first liquid can enter the target area after passing through the detection area; And / or, the method for identifying a single second target from a second liquid carrying the second target includes the following steps: detecting an optical signal within a detection area, and identifying the single second target based on the detection of the optical signal, wherein the second liquid can enter the target area after passing through the detection area.

33. The pairing method according to claim 30, characterized in that: The method for identifying a single first target object from a first liquid carrying the first target object comprises the following steps: detecting an electrical signal generated by an electrode disposed in a detection region, and identifying the single first target object based on the detected electrical signal, wherein the first liquid can enter the target region after passing through the detection region; And / or, the method for identifying a single second target object from a second liquid carrying the second target object includes the following steps: detecting an electrical signal generated by an electrode arranged in a detection area, and identifying the single second target object based on the detection of the electrical signal, wherein the second liquid can enter the target area after passing through the detection area.

34. The pairing method according to claim 30, characterized in that: The pairing method further includes the following steps: allowing the liquid droplet including the single first target object and the single second target object to pass through a fusion region, and applying an electric field to the fusion region to blend a fourth liquid into the liquid droplet.

Images