Microfluidic system for target object pairing

Abstract

The utility model discloses a microfluidic system for target object pairing, which comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer liquid flow channel, a matching flow channel and a pairing micro valve, a first micro valve, a second micro valve and a buffer liquid micro valve are arranged, the matching flow channel is communicated to the oil liquid flow channel, and the first flow channel, the second flow channel and the buffer liquid flow channel are all communicated to the matching flow channel; when a single first target object and a single second target object exist in the matching runner, the first micro valve and the second micro valve are in a closed state, and the matching micro valve and the buffer solution micro valve are in an open state; and the buffer liquid in the buffer liquid flow channel feeds the single first target object and the single second target object in the flow channel into the oil liquid in the oil liquid flow channel to form liquid drops. According to the utility model, other first target objects and / or other second target objects can be completely prevented from entering liquid drops, so that the success rate of packaging is improved, and the cell loss caused by multiple packaging is reduced.

Description

Technical Field

[0001] The utility model relates to the technical field of single cell sequencing, in particular to a microfluidic system for pairing of target objects. Background Art

[0002] Single cell RNA sequencing technology (scRNA-seq) reveals the heterogeneity of cells within a tissue. 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 a tissue, and has wide applications in fields such as cancer, reproduction, immunity, and development. Figure 1 There is shown a pairing system for pairing a single first target object with a single second target object, including a first flow channel 1, a second flow channel 2, an oil flow channel 3, a waste liquid flow channel 4, a sample flow channel 5, and a plurality of microvalves provided corresponding to each flow channel. The microvalves can control the on-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. In use, a first liquid containing a first target object is injected into the first flow channel 1, and a second liquid containing a second target object is injected into the second flow channel 2. If a single first target object does not appear in the first stop area 11, the first liquid is discharged through the waste liquid flow channel 4. Correspondingly, if a single second target object does not appear in the second stop area 21, the second liquid is also discharged through the waste liquid 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 both stop 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 jointly sent into the oil to form droplets through the first liquid and the second liquid respectively, 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 driving a single first target object and a single second target object into the oil are the first liquid and the second liquid respectively. Therefore, the following problems may occur: 1. When the first liquid drives a single first target object, subsequent first target objects will also be encapsulated into droplets together; 2. When the second liquid drives a single second target object, subsequent second target objects will also be encapsulated into droplets together; 3. When the first liquid drives a single first target object and the second liquid drives a single second target object, subsequent first target objects and subsequent second target objects will be encapsulated into droplets together, resulting in droplets containing multiple first target objects and / or multiple second target objects, causing multiple encapsulations and thus affecting subsequent detections.

[0004] 2. Figure 1 The shown solution will generate a large number of empty droplets, and it is necessary to sort the empty droplets from the normal droplets to avoid mixing, so the processing speed is slow and the efficiency is low. Summary of the Utility Model

[0005] The present utility model aims to solve at least one of the technical problems existing in the prior art. For this purpose, the present utility model provides a microfluidic system for object pairing.

[0006] According to the microfluidic system for object pairing in the first embodiment of the present utility model, it includes a first flow channel, a second flow channel, an oil flow channel, a buffer solution flow channel and a pairing flow channel. The pairing flow channel is connected to the oil flow channel, and the first flow channel, the second flow channel and the buffer solution flow channel are all connected to the pairing flow channel;

[0007] The microfluidic system further includes a pairing microvalve corresponding to the pairing flow channel, a first microvalve corresponding to the first flow channel, a second microvalve corresponding to the second flow channel, and a buffer solution microvalve corresponding to the buffer solution flow channel. The pairing microvalve is used to control the on-off of the pairing 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 solution microvalve is used to control the on-off of the buffer solution flow channel;

[0008] Wherein, when there is a single first target object and a single second target object in the pairing flow channel, the first microvalve and the second microvalve are in the closed state, and the pairing microvalve and the buffer solution microvalve are in the open state, so that the buffer solution in the buffer solution flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form droplets.

[0009] The microfluidic system for object pairing according to the embodiment of the present utility model has at least the following beneficial effects:

[0010] This embodiment is provided with a separate buffer flow channel. The buffer is used to push a single first target A and a single second target B into the oil, eliminating the need to use a first liquid and a second liquid to push the single first target A and the single second target B. Therefore, the first flow channel and the second flow channel can remain in a cut-off state during the encapsulation process, thus completely avoiding other first targets and / or other second targets from entering the droplets, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulations.

[0011] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel and a waste liquid micro-valve provided corresponding to the waste liquid flow channel. The waste liquid flow channel is communicated with the pairing flow channel, and the waste liquid micro-valve is used to control the on-off of the waste liquid flow channel.

[0012] Wherein, when the pairing micro-valve is in a closed state and the first micro-valve and the waste liquid micro-valve are in an open state, the liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel.

[0013] And / or, when the pairing micro-valve is in a closed state and the second micro-valve and the waste liquid micro-valve are in an open state, the liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel.

[0014] 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 the side of the pairing micro-valve away from the oil flow channel.

[0015] In other embodiments of the present invention, the first flow channel and the second flow channel are located on the same side of the pairing flow channel, and the waste liquid flow channel is located on the other side of the pairing flow channel.

[0016] In other embodiments of the present invention, the microfluidic system further includes at least one of the following solutions:

[0017] At least a first part of the first flow channel that is communicated with the pairing flow channel intersects with the pairing flow channel;

[0018] At least a second part of the second flow channel that is communicated with the pairing flow channel intersects with the pairing flow channel;

[0019] At least a third part of the waste liquid flow channel that is communicated with the pairing flow channel intersects with the pairing flow channel.

[0020] In other embodiments of the present invention, at least a fourth part of the buffer flow channel that is communicated with the pairing flow channel is coaxially arranged with the pairing flow channel.

[0021] In other embodiments of the present utility model, 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.

[0022] In other embodiments of the present utility model, the microfluidic system further includes a detection module, and the detection module is configured to identify a single first target in the first flow channel. Wherein, after the detection module identifies a single first target, both the first micro-valve and the paired micro-valve are in a closed state to keep the single first target in the paired flow channel;

[0023] And / or, the microfluidic system further includes a detection module, and the detection module is configured to identify a single second target in the second flow channel. Wherein, after the detection module identifies a single second target, both the second micro-valve and the paired micro-valve are in a closed state to keep the single second target in the paired flow channel.

[0024] In other embodiments of the present utility model, the microfluidic system further includes a waste liquid flow channel and a waste liquid micro-valve provided 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;

[0025] Wherein, when the detection module does not identify a single first target, the paired micro-valve is in a closed state and the first micro-valve and the waste liquid micro-valve 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;

[0026] And / or, when the detection module does not identify a single second target, the paired micro-valve is in a closed state and the second micro-valve and the waste liquid micro-valve 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.

[0027] In other embodiments of the present utility model, the detection module includes a camera and a controller, and the controller is configured to control the camera to take images;

[0028] Wherein, the image at least includes a first image of a first part where the first flow channel is communicated with the paired flow channel, and the controller is further configured to identify the single first target based on the first image;

[0029] And / or, the image at least includes a second image of a second part where the second flow channel is communicated with the paired flow channel, and the controller is further configured to identify the single second target based on the second image.

[0030] In other embodiments of the present utility model, the image at least includes a third image of the pairing flow channel, and the controller is configured to identify whether the single first target and / or the single second target exists in the pairing flow channel based on the third image.

[0031] In other embodiments of the present utility model, the detection module includes a first light source, a first light detection device and a controller. The controller is configured to control the first light source to emit a first detection light to the first flow channel. The first detection light can excite a first fluorescence after irradiating the single first target, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target.

[0032] 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, and when the second light detection device detects the second fluorescence, the controller identifies the single second target.

[0033] In other embodiments of the present utility model, 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 based on the signal detected by the first detection electrode.

[0034] 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 the signal detected by the second detection electrode.

[0035] In other embodiments of the present utility model, after the detection module identifies the single first target, the first micro-valve switches from the open state to the closed state after a set time delay, so that the single first target enters the pairing flow channel from the first flow channel.

[0036] And / or, after the detection module identifies the single second target, the second micro-valve switches from the open state to the closed state after a set time delay, so that the single second target enters the pairing flow channel from the second flow channel.

[0037] In other embodiments of the present utility model, the microfluidic system further includes a liquid injection flow channel, the liquid injection flow channel communicates with the oil liquid flow channel, a communication part between the paired flow channel and the oil liquid flow channel is defined as a first communication part, a communication part between the liquid injection flow channel and the oil liquid flow channel is defined as a second communication part, and the second communication part is located downstream of the first communication part along the flowing direction of the oil liquid in the oil liquid flow channel;

[0038] The microfluidic system further includes a fusion electrode, and the fusion electrode is used to apply an electric field to the second communication part so that the liquid in the liquid injection flow channel is fused into the liquid droplets flowing through the second communication part.

[0039] In other embodiments of the present utility model, the microfluidic system has a processing area, and the first flow channel, the second flow channel, the oil liquid flow channel, the buffer liquid flow channel, the paired flow channel and the liquid injection flow channel are all located in the processing area;

[0040] Wherein, the fusion electrode includes a first electrode and a second electrode, and the first electrode is arranged around the processing area.

[0041] In other embodiments of the present utility model, two ends of the first electrode are arranged in parallel with the second electrode, and the second electrode is arranged between two ends of the first electrode.

[0042] In other embodiments of the present utility model, the microfluidic system further includes an oil liquid micro valve corresponding to the oil liquid flow channel, and the oil liquid micro valve is used to control the on-off of the oil liquid flow channel.

[0043] In other embodiments of the present utility model, the microfluidic system further includes a first micro valve control flow channel, and the first micro valve includes a diaphragm arranged between the first flow channel and the first micro valve control flow channel, and the diaphragm can be driven to protrude towards the first flow channel to be in a closed state;

[0044] Wherein, the inner wall of the first flow channel is an arc-shaped inner wall.

[0045] In other embodiments of the present utility model, the microfluidic system includes a microfluidic chip, and the microfluidic chip includes a base layer, a control layer and a flow channel layer which are sequentially stacked;

[0046] Wherein, the first flow channel, the second flow channel, the oil liquid flow channel, the buffer liquid flow channel and the paired flow channel are arranged in the flow channel layer;

[0047] The control layer is provided with the paired micro valve, the first micro valve, the second micro valve and the buffer liquid micro valve.

[0048] In other embodiments of the present utility model, the first target is a cell and the second target is a microsphere.

[0049] In other embodiments of the present utility model, the microsphere is a magnetic microsphere.

[0050] In other embodiments of the present utility model, the microsphere is a fluorescent magnetic microsphere.

[0051] In other embodiments of the present utility model, the first target is a first cell and the second target is a second cell.

[0052] According to the microfluidic system for target pairing in the second embodiment of the present utility model, the microfluidic system includes a first flow channel, a second flow channel, an oil flow channel, a buffer solution flow channel and a pairing flow channel. The pairing flow channel communicates with the oil flow channel. Both the first flow channel and the second flow channel communicate with the pairing flow channel. The buffer solution flow channel communicates with the first flow channel and the second flow channel respectively. The first flow channel has a first part communicating with the pairing flow channel, and the second flow channel has a second part communicating with the pairing flow channel.

[0053] The microfluidic system further includes a first microvalve corresponding to the first flow channel, a second microvalve corresponding to the second flow channel and a buffer solution microvalve corresponding to the buffer solution 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 solution microvalve is used to control the on-off of the buffer solution flow channel.

[0054] Wherein, when there is a single first target in the first part and a single second target in the second part, the first microvalve and the second microvalve are in the closed state, and the buffer solution microvalve is in the open state, so that the buffer solution in the buffer solution flow channel sends the single first target in the first part and the single second target in the second part into the oil in the oil flow channel through the pairing flow channel to form droplets.

[0055] In other embodiments of the present utility model, 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. The waste liquid flow channel and the droplet flow channel communicate with the oil flow channel respectively. 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.

[0056] Wherein, when the first microvalve and the waste liquid microvalve are in the open state and the droplet microvalve is in the closed state, the liquid in the first flow channel can flow out through the pairing flow channel, the oil flow channel and the waste liquid flow channel.

[0057] And / or, when the second micro-valve and the waste liquid micro-valve are in an open state and the droplet micro-valve is in a closed state, the liquid in the second flow channel can flow out through the paired flow channel, the oil liquid flow channel and the waste liquid flow channel.

[0058] In other embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel, a droplet flow channel, a waste liquid micro-valve provided corresponding to the waste liquid flow channel, and a droplet micro-valve provided corresponding to the droplet flow channel. The waste liquid flow channel and the droplet flow channel are respectively communicated with the oil liquid flow channel. The waste liquid micro-valve is used to control the on-off of the waste liquid flow channel, and the droplet micro-valve is used to control the on-off of the droplet flow channel.

[0059] Wherein, when droplets are formed in the oil liquid in the oil liquid flow channel, the waste liquid micro-valve is in a closed state and the droplet micro-valve is in an open state, so that the droplets are discharged through the droplet 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 micro-valve provided corresponding to the waste liquid flow channel, and a droplet micro-valve provided corresponding to the droplet flow channel. The waste liquid micro-valve is used to control the on-off of the waste liquid flow channel, and the droplet micro-valve is used to control the on-off of the droplet flow channel.

[0061] Wherein, the paired flow channel is communicated to the inlet end of the oil liquid flow channel, and the waste liquid flow channel and the droplet flow channel are both communicated to the outlet end of the oil liquid flow channel.

[0062] In other embodiments of the present invention, the microfluidic system further includes a detection module, and the detection module is configured to identify a single first target in the first flow channel. Wherein, after the detection module identifies a single first target, the first micro-valve is in a closed state to keep the single first target in the first part.

[0063] And / or, the microfluidic system further includes a detection module, and the detection module is configured to identify a single second target in the second flow channel. Wherein, after the detection module identifies a single second target, the second micro-valve is in a closed state to keep the single second target in the second part.

[0064] The additional aspects and advantages of the present invention will be partly given in the following description, partly will become obvious from the following description, or will be understood through the practice of the present invention. Description of the Drawings

[0065] The present invention will be further described below in conjunction with the drawings and embodiments, wherein:

[0066] Figure 1 Schematic diagram of a pairing system in the related art;

[0067] Figure 2 Schematic diagram of the microfluidic system in the first embodiment of the present invention;

[0068] Figure 3 is Figure 2 Enlarged schematic diagram showing the pairing flow channel in

[0069] Figure 4 Flow chart of the pairing of the first target object and the second target object by the microfluidic system in the first embodiment of the present invention;

[0070] Figure 5 Schematic diagram of the microfluidic system combined with the electrode detection module in the first embodiment of the present invention;

[0071] Figure 6 Schematic diagram of the microfluidic system combined with the electrofusion module in the first embodiment of the present invention;

[0072] Figure 7 is Figure 6 Enlarged schematic diagram showing the electrofusion process in

[0073] Figure 8 Schematic diagram of the microvalve of the microfluidic system in the first embodiment of the present invention in the open state and the closed state;

[0074] Figure 9 Exploded schematic diagram of the microfluidic chip in the first embodiment of the present invention;

[0075] Figure 10 Schematic diagram of the microfluidic system in the second embodiment of the present invention.

[0076] Reference numerals:

[0077] First flow channel 1, second flow channel 2, oil flow channel 3, waste liquid flow channel 4, sample flow channel 5;

[0078] Microfluidic chip 100, base layer 110, control layer 120, first micro-valve 121, diaphragm 1211, second micro-valve 122, oil micro-valve 123, buffer micro-valve 124, waste liquid micro-valve 125, paired micro-valve 126, flow channel layer 130, first flow channel 131, first part 1311, second flow channel 132, second part 1321, oil flow channel 133, first communication part 1331, second communication part 1332, buffer flow channel 134, fourth part 1341, waste liquid flow channel 135, third part 1351, paired flow channel 136, liquid injection flow channel 137, first micro-valve control flow channel 138, first injection port 1391, second injection port 1392, third injection port 1393;

[0079] First detection light 210, second detection light 220, first detection electrode 230, second detection electrode 240;

[0080] Fusion electrode 300, first electrode 310, second electrode 320;

[0081] Single first target A;

[0082] Single second target B;

[0083] Droplet C. Detailed implementation mode

[0084] The embodiments of the present invention will be described in detail below. The examples of the embodiments are shown in the drawings, where the same or similar reference numerals represent the same or similar elements or elements with the same or similar functions throughout. The embodiments described below with reference to the drawings are exemplary and are only used to explain the present invention and should not be construed as a limitation of the present invention.

[0085] In the description of the present invention, it should be understood that for the orientation description, such as the orientation or positional relationship indicated by up, down, front, back, left, right, etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention.

[0086] In the description of the present invention, the meaning of several is more than one, the meaning of multiple is more than two, greater than, less than, exceeding, etc. are understood as not including the present number, and above, below, within, etc. are understood as including the present number. If there is a description of first and second, it is only for the purpose of distinguishing technical features and should not be construed as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features or implicitly indicating the sequence relationship of the indicated technical features.

[0087] In the description of the present utility model, unless otherwise clearly defined, terms such as "set", "installed", "connected", etc. should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above terms in the present utility model in combination with the specific content of the technical solution.

[0088] In the description of the present utility model, the description with reference to terms such as "one embodiment", "some embodiments", "schematic embodiments", "examples", "specific examples", or "some examples", etc. means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present utility model. In this specification, the schematic descriptions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0089] The first embodiment of the present utility model proposes a microfluidic system for target pairing, referring to Figures 2 to 4 , which 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. Among them, the first flow channel 131 is used for the first liquid containing the first target to pass through, the second flow channel 132 is used for the second liquid containing the second target to pass through, the buffer flow channel 134 is used for the buffer to pass through, the oil flow channel 133 is used for the oil that is immiscible with the first liquid, the second liquid, and the buffer to pass through, and the pairing flow channel 136 is used for a single first target and a single second target to stay. The pairing flow channel 136 communicates with the oil flow channel 133, and the first flow channel 131, the second flow channel 132, and the buffer flow channel 134 all communicate with the pairing flow channel 136. In some further embodiments, the microfluidic system further includes a waste liquid flow channel 135, and the waste liquid flow channel 135 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 for illustration. Those skilled in the art can understand that the first target can be a cell, and the second target can also be a cell.

[0090] The microfluidic system of this embodiment further includes a plurality of microvalves, specifically including a paired microvalve 126 corresponding to the paired flow channel 136, a first microvalve 121 corresponding to the first flow channel 131, a second microvalve 122 corresponding to the second flow channel 132, and a buffer microvalve 124 corresponding to the buffer solution flow channel 134. Among them, 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 solution flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the so-called first microvalve 121 controlling the on-off 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 the open state, the first flow channel 131 is in an unobstructed state, and the first liquid can flow in the first flow channel 131. When the first microvalve 121 is in the closed state, the first flow channel 131 is in a cut-off state, and the first liquid cannot flow in the first flow channel 131.

[0091] In this embodiment, referring to Figure 4 , when there is a single first target A and a single second target B in the paired flow channel 136, the first microvalve 121 and the second microvalve 122 are in the closed state (the microvalve is filled with black to indicate the closed state), and the paired microvalve 126 and the buffer microvalve 124 are in the open state (the microvalve is filled with gray to indicate the open state). At this time, the buffer solution in the buffer solution flow channel 134 can send the single first target A and the single second target B in the paired flow channel 136 into the oil in the oil flow channel 133 to form a droplet C.

[0092] As can be seen from the above, this embodiment is provided with a separate paired flow channel 136 for temporarily storing a single first target A and a single second target B, and a separate buffer solution flow channel 134 is provided. The buffer solution is used to push the single first target A and the single second target B into the oil, without using the first liquid and the second liquid to push the single first target A and the single second target B. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in the cut-off state during the encapsulation process, so as to completely avoid 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 encapsulations.

[0093] On the basis of the first embodiment, referring to Figure 2 , Figure 3, in some embodiments of the present utility model, the microfluidic system further includes a waste liquid flow channel 135, and the waste liquid flow channel 135 is used to discharge the first liquid and the second liquid, and the waste liquid flow channel 135 communicates with the pairing flow channel 136. In addition, the microfluidic system further includes a waste liquid micro-valve 125 arranged corresponding to the waste liquid flow channel 135, and the waste liquid micro-valve 125 is used to control the on-off of the waste liquid flow channel 135. When the pairing micro-valve 126 is in the closed state and the first micro-valve 121 and the waste liquid micro-valve 125 are in the open state, the first liquid in the first flow channel 131 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135. It should be noted that the first target will gradually approach and reach the pairing flow channel 136 following the flow of the first liquid. When the first target has not reached the pairing flow channel 136, the first flow channel 131 will continuously discharge the first liquid, and these first liquids need 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 pairing flow channel 136, and then enter the waste liquid flow channel 135 for discharge. In other words, the first liquid in this embodiment will not pass through the oil liquid flow channel 133 when being discharged, as compared with Figure 1 the solution shown, this solution also has the following advantages:

[0094] 1. Figure 1 In the solution shown, since the waste liquid discharge needs to pass through the oil liquid flow channel 3, it will inevitably carry away the oil liquid in the oil liquid flow channel 3, resulting in waste of the oil liquid. However, in this embodiment, the first liquid and the second liquid will not pass through the oil liquid flow channel 133 when being discharged, so the oil liquid in the oil liquid flow channel 133 will not be carried away, and the usage amount of the oil liquid can be reduced.

[0095] 2. Figure 1 In the solution shown, also because the waste liquid discharge needs to pass through the oil liquid flow channel 3, the oil liquid flow channel 3 needs to be closed when discharging the waste liquid. After the pairing is completed, the first flow channel 1, the second flow channel 2, and the oil liquid flow channel 3 need to be opened synchronously, otherwise it will cause the oil liquid flow channel 3 not to provide oil liquid in time and droplets cannot be formed. Therefore Figure 1 in the solution shown, the control requirements for the micro-valves corresponding to the first flow channel 1, the second flow channel 2, and the oil liquid flow channel 3 are extremely high, resulting in frequent occurrence of the situation where the encapsulation of the target fails, further resulting in loss of the target. However, in this embodiment, the first liquid and the second liquid will not pass through the oil liquid flow channel 133 when being discharged, so the oil liquid flow channel 133 can always be filled with oil liquid. After the pairing is completed, only the buffer liquid micro-valve 124 and the pairing micro-valve 126 need to be opened. Even if the buffer liquid micro-valve 124 and the pairing micro-valve 126 are not synchronized, it will not cause the encapsulation to fail.

[0096] 3. Figure 1In the shown solution, after the oil flow channel 3 is closed, there will still be some residual oil inside. When the waste liquid passes through this residual oil, empty droplets will be generated, and the empty droplets will cause the mixing of normal droplets. Therefore, the empty droplets and normal droplets need to enter different flow channels with the assistance of the micro-valve in the waste liquid flow channel 4 and the micro-valve in the sample flow channel 5. However, this also poses extremely high requirements for the control of the two micro-valves. Otherwise, losses will occur. For example, after the droplets are formed, if the micro-valve in the waste liquid flow channel 4 fails to close in time and the micro-valve in 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, when the first liquid and the second liquid are discharged, they will not pass through the oil flow channel 133. The encapsulated droplet C can reach the subsequent storage position as it flows with the 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 also avoids the loss of the target due to this part of the reason.

[0097] 4. As described above, Figure 1 In the shown solution, a large number of empty droplets will be generated. Therefore, sorting needs to be carried out through the switching of valves, which will greatly affect the processing speed. Compared with Figure 1 the solution, in the microfluidic chip structure of this embodiment, a large number of empty droplets are avoided from being generated, and sorting operations for empty droplets and sample droplets are not required. Therefore, the pairing efficiency can be improved. For example, 5 to 10 droplets can be generated per second, that is, 18,000 to 36,000 droplets per hour. In addition, the microfluidic chip structure of this embodiment can also significantly reduce the control difficulty of the micro-valve.

[0098] In some embodiments, the microfluidic system further includes power elements such as pumps for driving the buffer solution to flow. In some specific embodiments, the microfluidic system includes a high-speed pump that can achieve the high-speed flow and stop of the buffer solution, so as to adapt to high-speed pairing.

[0099] Based on the first embodiment, with reference to Figure 2 、 Figure 3 , in some embodiments of the present utility model, the waste liquid flow channel 135 is directly connected to the pairing flow channel 136. The microfluidic system further includes a waste liquid micro-valve 125 provided corresponding to the waste liquid flow channel 135, and the waste liquid micro-valve 125 is used to control the on-off of the waste liquid flow channel 135. When the pairing micro-valve 126 is in the closed state and the second micro-valve 122 and the waste liquid micro-valve 125 are in the open state, the liquid in the second flow channel 132 can flow out through the pairing flow channel 136 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 elaborated here.

[0100] When the waste liquid flow channel 135 is directly connected to the pairing flow channel 136, with reference to Figure 2 、 Figure 3, in some embodiments of the present utility model, the first flow channel 131, the second flow channel 132, the buffer liquid flow channel 134 and the waste liquid flow channel 135 are all located on the side of the paired micro-valve 126 away from the oil liquid flow channel 133. Thus, before the pairing is completed, the first liquid, the second liquid, etc. can be prevented from entering the oil liquid flow channel 133. Specifically in the illustrated embodiment, the oil liquid flow channel 133 is distributed horizontally, the paired flow channel 136 is distributed vertically and its lower end is communicated with the oil liquid flow channel 133, then the paired micro-valve 126 is roughly located at the lower end of the paired flow channel 136, and the first flow channel 131, the second flow channel 132, the buffer liquid flow channel 134 and the waste liquid flow channel 135 are all located above the paired micro-valve 126.

[0101] Combined with the above structure, the control of each micro-valve is described as follows:

[0102] 1. Pairing process

[0103] The buffer liquid micro-valve 124 and the paired micro-valve 126 are closed, the first micro-valve 121, the second micro-valve 122 and the waste liquid micro-valve 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 recognized, the first micro-valve 121 is closed, and the single first target stops in the paired flow channel 136 (for example Figure 4 in b). When a single second target is recognized, the second micro-valve 122 is closed, and the single second target stops in the paired flow channel 136 (for example Figure 4 in c). After a single first target and a single second target both stop in the paired flow channel 136, the waste liquid micro-valve 125 is closed (for example Figure 4 in c).

[0104] 2. Encapsulation process

[0105] After the first micro-valve 121, the second micro-valve 122 and the waste liquid micro-valve 125 are closed, the buffer liquid micro-valve 124 and the paired micro-valve 126 are opened, and the buffer liquid sends the single first target and the single second target in the paired flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form droplets (for example Figure 4 in d).

[0106] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, referring to Figure 3 , in some embodiments of the present utility model, along the extending direction of the paired flow channel 136, the waste liquid flow channel 135 is located between the first flow channel 131 and the second flow channel 132. Thus, when the first liquid is discharged, it will not drive the already stationary single second target B. Similarly, when the second liquid is discharged, it will not drive the already stationary single second target A, and the discharge of the first liquid and the second liquid can be carried out synchronously.

[0107] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, refer to Figure 3 , 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 paired flow channel 136, and the waste liquid flow channel 135 is located on the other side of the paired flow channel 136. Specifically, in the embodiment shown in Figure 3 , the first flow channel 131 and the second flow channel 132 are located on the left side of the paired flow channel 136, and the waste liquid flow channel 135 is located on the right side of the paired flow channel 136. In this way, the first liquid and the second liquid can flow in substantially the same direction, which is convenient for discharging the waste liquid.

[0108] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, refer to Figure 3 , in the present invention, at least the first part 1311 of the first flow channel 131 that is communicated with the paired flow channel 136 intersects with the paired flow channel 136. Specifically, refer to the embodiment shown in Figure 3 , the first part 1311 is perpendicular to the paired flow channel 136.

[0109] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, refer to Figure 3 , in the present invention, at least the second part 1321 of the second flow channel 132 that is communicated with the paired flow channel 136 intersects with the paired flow channel 136. Specifically, refer to the embodiment shown in Figure 3 , the second part 1321 is perpendicular to the paired flow channel 136.

[0110] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, refer to Figure 3 , at least the third part 1351 of the waste liquid flow channel 135 that is communicated with the paired flow channel 136 intersects with the paired flow channel 136. Specifically, refer to the embodiment shown in Figure 3 , the third part 1351 is perpendicular to the paired flow channel 136.

[0111] When the waste liquid flow channel 135 is directly communicated with the paired flow channel 136, refer to Figure 3 , at least the fourth part 1341 of the buffer liquid flow channel 134 that is communicated with the paired flow channel 136 is coaxially arranged with the paired flow channel 136. In this way, the buffer liquid can enter the paired flow channel 136 along the same direction and drive a single first target A and a single second target B into the oil liquid. It should be noted that in this embodiment, the buffer liquid flow channel 134 and the paired flow channel 136 can be two parts of a whole flow channel. Taking the example shown in Figure 3 , the lower part of the vertical flow channel is the paired flow channel 136, and the upper part is the buffer liquid flow channel 134. For the convenience of reading, the range of the paired flow channel 136 is roughly marked by a dotted line box in the figure, but the dotted line box should not be understood as a specific limitation on the shape and length of the paired flow channel 136.

[0112] It can be understood that the above embodiments can be combined, that is, the first part 1311, the second part 1321, and the third part 1351 are all arranged to intersect with the paired flow channel 136, and the fourth part 1341 is arranged coaxially with the paired flow channel 136.

[0113] 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 A in the first flow channel 131. Wherein, when the detection module identifies a single first target A, both the first micro-valve 121 and the paired micro-valve 126 are in a closed state to keep the single first target A in the paired flow channel 136. It should be noted that in this embodiment, the first micro-valve 121 being in a closed state specifically means switching from an open state to a closed state, and the paired micro-valve 126 being in a closed state specifically means remaining in a closed state.

[0114] In some other embodiments, the detection module is configured to identify a single second target B in the second flow channel 132. Wherein, when the detection module identifies a single second target B, both the second micro-valve 122 and the paired micro-valve 126 are in a closed state to keep the single second target B in the paired flow channel 136. It should be noted that in this embodiment, the second micro-valve 122 being in a closed state specifically means switching from an open state to a closed state, and the paired micro-valve 126 being in a closed state specifically means remaining in a closed state.

[0115] When identifying a single first target A through the detection module, in some embodiments of the present invention, the microfluidic system further includes a waste liquid micro-valve 125 corresponding to the waste liquid flow channel 135, and the waste liquid micro-valve 125 is used to control the on-off of the waste liquid flow channel 135. Wherein, when the detection module does not identify a single first target A, the paired micro-valve 126 is in a closed state and the first micro-valve 121 and the waste liquid micro-valve 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 micro-valve 126 being in a closed state specifically means remaining in a closed state, and the first micro-valve 121 and the waste liquid micro-valve 125 being in an open state specifically means remaining in an open state.

[0116] In some embodiments of the present utility model, when a single second target B is identified by the detection module, when the detection module fails to identify a single second target B, the pairing micro-valve 126 is in a closed state and the second micro-valve 122 and the waste liquid micro-valve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135. It should be noted that in this embodiment, the pairing micro-valve 126 being in a closed state specifically means remaining in the closed state, and the second micro-valve 122 and the waste liquid micro-valve 125 being in an open state specifically means remaining in the open state.

[0117] In some embodiments of the present utility model, when a single first target A is identified by the detection module, the detection module is specifically a vision detection module, which includes a camera and a controller, and the controller is configured to control the camera to capture images. In this embodiment, the image captured by the camera at least includes a first image of a first part 1311 where the first flow channel 131 communicates with the pairing flow channel 136. After the camera captures the image, the controller is further configured to identify a single first target A based on the first image. In other words, the identification operation of the single first target A has been completed before it enters the pairing flow channel 136. It should be noted that the microspheres in this embodiment can be magnetic microspheres, which can be adsorbed by magnetic parts for recycling.

[0118] In other embodiments, the image captured by the camera at least includes a second image of a second part 1321 where the second flow channel 132 communicates with the pairing flow channel 136, and the controller is further configured to identify a single second target B based on the second image. In other words, the identification operation of the single second target B has been completed before it enters the pairing flow channel 136.

[0119] 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), classifies the cropped target image through a model trained by a convolutional neural network, and makes a judgment based on the result of the classification output and controls the corresponding micro-valve.

[0120] In some embodiments of the present utility model, when the detection module identifies a single first target A through image recognition, the image captured by the camera at least further includes a third image of the pairing flow channel 136, and the controller is configured to identify whether there is a single first target A 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 A has entered the pairing flow channel 136.

[0121] In some other embodiments, the image captured by the camera further includes a third image of the paired channel 136. The controller is configured to identify whether there is a single second target B in the paired 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 B has entered the paired channel 136.

[0122] 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 perform 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 the single second target B has reached the paired channel 136, or identifying a single first target B and determining whether the single first target A has reached the paired channel 136, or determining whether the single first target A and the single second target B have reached the paired channel 136.

[0123] 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 a first detection light 210 to the first channel 131. The first detection light 210 can excite a 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. When 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 stained with a fluorescent substance, which can emit fluorescence under the excitation of an external light source.

[0124] Among them, referring to Figure 4 , the first light source projects the first detection light 210 to a set position of the first channel 131. When no cell reaches the set position, the first light detection device will not receive an optical signal. When a cell reaches the set position, the cell is excited by the first detection light 210 to generate fluorescence. When the first light detection device detects the first fluorescence, the detection device identifies the single first target A.

[0125] When a single second target B is identified by the detection module, in some embodiments of the present invention, the detection module is specifically a fluorescence detection module, including 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 220 to the second flow channel 132. The second detection light 220 can excite a second fluorescence after irradiating the single second target B. When the second light detection device detects the second fluorescence, the controller identifies the single second target B.

[0126] Combined with Figure 4 Describe the fluorescence-based first target A / second target B identification scheme:

[0127] 1. Identification of the first target A

[0128] The first micro-valve 121 is in an open state, and the first liquid continuously flows through the first detection position irradiated by the first detection light 210. When a single first target 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. After the first fluorescence is received by the first light detection device, an electrical signal is generated. The controller identifies the single first target A based on the electrical signal, and then controls the first micro-valve 121 to switch to a closed state, so that the single first target A stops in the pairing flow channel 136.

[0129] 2. Identification of the second target

[0130] The second micro-valve 122 is in an open state, and the second liquid continuously flows through the second detection position irradiated by the second detection light 220. When a single second target 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. After the second fluorescence is received by the second light detection device, an electrical signal is generated. The controller identifies the single second target B based on the electrical signal, and then controls the second micro-valve 122 to switch to a closed state, so that the single second target B stops in the pairing flow channel 136.

[0131] It should be noted that the first light source and the second light source can be lasers with different wavelengths.

[0132] When a single first target A is identified by the detection module, in some embodiments of the present invention, the detection module is specifically an electrode detection module. Refer to Figure 5, which includes a first detection electrode 230 and a controller. The first detection electrode 230 extends into the first flow channel 131. When a single first target A passes by 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 side by side. 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. In addition, in this embodiment, the signal detected by the first detection electrode 230 can be changes in amplitude and phase difference. It should be noted that the microspheres in this embodiment can be magnetic microspheres, which can be adsorbed by magnetic members for recovery.

[0133] When identifying a single second target B through the detection module, in some embodiments of the present invention, the detection module is specifically an electrode detection module. Refer to Figure 5 , which includes a second detection electrode 240 and a controller. The second detection electrode 240 extends into the second flow channel 132. The controller is configured to identify the single second target B based on the signal detected by the second detection electrode 240.

[0134] The second detection electrode 240 can be understood by referring to the first detection electrode 230.

[0135] When identifying a single first target A through the detection module, in some embodiments of the present invention, after the detection module identifies a single first target A, the first micro-valve 121 switches from the open state to the closed state after a set delay time, so that the single first target A enters the pairing flow channel 136 from the first flow channel 131. Refer to Figure 4 、 Figure 5 , the identification position of the single first target A is at a certain distance from the pairing flow channel 136. In this embodiment, the method of delaying the closing of the first micro-valve 121 is adopted to ensure that the single first target A can enter the pairing flow channel 136. It should be noted that the set delay time can be determined according to the distance between the identification position and the pairing flow channel 136 and the flow rate of the first liquid.

[0136] When identifying a single second target B through the detection module, in some embodiments of the present invention, after the detection module identifies a single second target B, the second micro-valve 122 switches from the open state to the closed state after a set delay time, so that the single second target B enters the pairing flow channel 136 from the second flow channel 132. Refer to Figure 4 、 Figure 5, the recognition position for identifying a single second target B has a certain distance from the pairing channel 136. In this embodiment, the second micro-valve 122 is closed in a delayed manner to ensure that a single second target B can enter the pairing channel 136. It should be noted that the set delay time can be determined according to the distance between the recognition position and the pairing channel 136 and the flow rate of the second liquid.

[0137] Based on the first embodiment, with reference to Figure 6 , Figure 7 , in some embodiments of the present invention, the microfluidic system further includes a liquid injection system, and the liquid injection system is used to inject liquid into the droplet C, such as injecting reverse transcription liquid into the droplet C. Specifically, the microfluidic system further includes a liquid injection channel 137, and the liquid injection channel 137 is communicated with the oil liquid channel 133. Among them, the communication part between the pairing channel 136 and the oil liquid channel 133 is defined as the first communication part 1331, and the communication part between the liquid injection channel 137 and the oil liquid channel 133 is defined as the second communication part 1332. The second communication part 1332 is located downstream of the first communication part 1331 along the flowing direction of the oil liquid in the oil liquid channel 133.

[0138] The microfluidic system further includes a fusion electrode 300, and the fusion electrode 300 is used to apply an electric field to the second communication part 1332. When the droplet C passes through the second communication part 1332, the liquid in the liquid injection channel 137 is fused into the droplet C under the action of the electric field. Among them, the liquid in the liquid injection channel 137 is also insoluble in the oil liquid, and the pressure in the liquid injection channel 137 is relatively small, so that the liquid in the liquid injection channel 137 slightly protrudes into the oil liquid channel 133. In this way, when the droplet C passes through the second communication part 1332, it can contact the liquid in the liquid injection channel 137, thus facilitating their fusion.

[0139] When the microfluidic system further includes a liquid injection system, with reference to Figure 6 , Figure 7 , in some embodiments of the present invention, the flow channel layer 130 has a processing area, and the first flow channel 131, the second flow channel 132, the oil liquid channel 133, the buffer liquid channel 134, the waste liquid channel 135, the pairing channel 136 and the liquid injection channel 137 are all located in the processing area. It should be noted that the processing area is an area for auxiliary understanding and does not mean that the microfluidic system must have an area with obvious boundaries and can be recognized.

[0140] In this embodiment, the fusion electrode 300 includes a first electrode 310 and a second electrode 320. The first electrode 310 is disposed around the processing area to achieve a better electrofusion effect. In some specific embodiments, when the microfluidic system includes the microfluidic chip 100, an electrode channel is formed on the flow channel layer 130 of the microfluidic chip 100, and a metal rod is inserted into the electrode channel. After the metal rod is heated, it melts and fills the electrode channel, and the first electrode 310 and the second electrode 320 are formed after cooling. In some embodiments, the electrode channel has an electrode injection port for injecting the metal rod, so as to Figure 6 take the shown one 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 be used as an exhaust port, so as to facilitate the metal liquid to fill the entire electrode channel.

[0141] When the fusion electrode 300 includes the first electrode 310 and the second electrode 320, and the first electrode 310 surrounds the processing area, referring to Figure 7 , in some embodiments of the present invention, both ends of the first electrode 310 are arranged in parallel with the second electrode 320, and the second electrode 320 is arranged between both ends of the first electrode 310 to achieve a better electrofusion effect.

[0142] On the basis of the first embodiment, referring to Figure 2 , in some embodiments of the present invention, the microfluidic chip 100 further includes an oil micro-valve 123 corresponding to the oil flow channel 133. The oil micro-valve 123 is used to control the on-off of the oil flow channel 133. When the oil micro-valve 123 is opened, the oil in the oil flow channel 133 flows, driving the droplet C to move downstream. Specifically in the illustrated embodiment, the oil micro-valve 123 is located upstream of the first communication part 1331 along the flow direction of the oil in the oil flow channel 133.

[0143] On the basis of the first embodiment, in some embodiments of the present invention, the microfluidic system further includes a first micro-valve control channel 138. Referring to Figure 8 , the first micro-valve 121 includes a diaphragm 1211 disposed between the first flow channel 131 and the first micro-valve control channel 138. When the first micro-valve 121 is in the 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 flow channel 131; when the diaphragm 1211 is driven to protrude towards the first flow channel 131 to be in the closed state as shown in b in Figure 8 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first flow channel 131, and the first liquid cannot flow in the first flow channel 131.

[0144] 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 into the first flow channel 131, thereby ensuring the cut-off effect.

[0145] It should be noted that in addition to the aforementioned first micro-valve control flow channel 138, the microfluidic system further includes micro-valve control flow channels corresponding to the second micro-valve 122, oil micro-valve 123, buffer micro-valve 124, waste liquid micro-valve 125, and pairing micro-valve 126. Correspondingly, the second micro-valve 122, oil micro-valve 123, buffer micro-valve 124, waste liquid micro-valve 125, and pairing micro-valve 126 all include diaphragms. The specific settings and control methods thereof can be understood by referring to the first micro-valve control flow channel 138 and will not be elaborated herein.

[0146] It should also be noted that the power for driving the protrusion of the diaphragm 1211 can be air pressure. In this embodiment, the first micro-valve control flow channel 138 is filled with liquid, and the external air source drives the liquid in the first micro-valve control flow channel 138 to flow, thereby pushing the diaphragm 1211 to protrude or reset. Compared with the direct air pressure driving method, since the liquid is difficult to compress, this method can achieve the rapid response of the diaphragm 1211, thus adapting to high-speed pairing.

[0147] Based on the first embodiment, referring to Figure 9 , in some embodiments of the present invention, the microfluidic system includes a microfluidic chip 100. The microfluidic chip 100 includes a base layer 110, a control layer 120, and a flow channel layer 130 that are sequentially stacked. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS).

[0148] Among them, the flow channel layer 130 has the aforementioned first flow channel 131, second flow channel 132, oil flow channel 133, buffer flow channel 134, waste liquid flow channel 135, and pairing flow channel 136. The control layer 120 has the aforementioned pairing micro-valve 126, first micro-valve 121, second micro-valve 122, and buffer micro-valve 124, as well as micro-valve control flow channels corresponding to each micro-valve.

[0149] Based on the first embodiment, in some embodiments of the present invention, the first target A is a cell, and the second target B is a microsphere. In some embodiments, the microsphere can be further set as a magnetic microsphere, and the RNA released after cell lysis can be adsorbed on the surface of the microsphere. Subsequently, the microsphere can be collected by a magnetic member, and then the RNA can be collected. In some embodiments, the microsphere can be further set as a fluorescent magnetic microsphere so as to emit fluorescence under the excitation of external light.

[0150] Based on the first embodiment, in some embodiments of the present utility model, the first target A is the first cell, and the second target B is the second cell, which is used to study the interaction effect between cells.

[0151] The second embodiment of the present utility model proposes a microfluidic system for target pairing, and its differences from the first embodiment include: in the microfluidic system of the first embodiment, the first target A and the second target B stop in the pairing channel 136, while in this embodiment, the first target A and the second target B stop in the first channel 131 and the second channel 132.

[0152] Refer to Figure 10 , the microfluidic system includes a first channel 131, a second channel 132, an oil channel 133, a buffer channel 134 and a pairing channel 136. Among them, the first channel 131 is used for the first liquid containing the first target to pass through, the second channel 132 is used for the second liquid containing the second target to pass through, the buffer channel 134 is used for the buffer to pass through, and the oil channel 133 is used for the oil that is not miscible with the first liquid, the second liquid, and the buffer to pass through. The pairing channel 136 is connected to the oil channel 133, both the first channel 131 and the second channel 132 are connected to the pairing channel 136, the buffer channel 134 is respectively connected to the first channel 131 and the second channel 132, the first channel 131 has a first part 1311 connected to the pairing channel, and the second channel 132 has a second part 1321 connected to the pairing 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.

[0153] The microfluidic system of this embodiment further includes a plurality of microvalves, specifically including a first microvalve 121 corresponding to the first channel 131, a second microvalve 122 corresponding to the second channel 132, and a buffer microvalve 124 corresponding to the buffer channel 134. The first microvalve 121 is used to control the on-off of the first channel 131, the second microvalve 122 is used to control the on-off of the second channel 132, and the buffer microvalve 124 is used to control the on-off of the buffer channel 134. The on-off here can be understood with reference to the first embodiment.

[0154] In this embodiment, refer to Figure 10 , when there is a single first target A in the first part 1311 and a single second target B in the second part 1321, the first microvalve 121 and the second microvalve 122 are in the closed state, and the buffer microvalve 124 is in the open state, so that the buffer in the buffer channel 134 sends the single first target A in the first part 1311 and the single second target B in the second part 1321 into the pairing channel 136 first, and then into the oil in the oil channel 133 together to form droplets.

[0155] As can be seen from the above, in this embodiment, the first part 1311 of the first flow channel 131 is provided for temporarily storing a single first target A, the second part 1321 of the second flow channel 132 is provided for temporarily storing a single second target B, and a separate buffer liquid flow channel 134 is provided. The buffer liquid is used to push the single first target A and the single second target B into the oil liquid, without using the first liquid and the second liquid to push the single first target A and the single second target B. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in the cut-off state during the encapsulation process, so as to completely avoid 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 encapsulations.

[0156] Based on the second embodiment, referring to Figure 10 , in some embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel 135 and a droplet flow channel 139. The waste liquid flow channel 135 is used to discharge the excess first liquid and second liquid, and the droplet flow channel 139 is used to discharge the droplet C. Both the waste liquid flow channel 135 and the droplet flow channel 139 are communicated with the oil liquid flow channel 133. In addition, the microfluidic system further includes a waste liquid micro-valve 125 provided corresponding to the waste liquid flow channel 135 and a droplet micro-valve 127 provided corresponding to the droplet flow channel 139. The waste liquid micro-valve 125 is used to control the on-off of the waste liquid flow channel 135, and the droplet micro-valve 127 is used to control the on-off of the droplet flow channel 139. When the first micro-valve 121 and the waste liquid micro-valve 125 are in the open state and the droplet micro-valve 127 is in the closed state, the first liquid in the first flow channel 131 can flow out through the pairing flow channel 136, the oil liquid flow channel 133 and the waste liquid flow channel 135.

[0157] Based on the second embodiment, referring to Figure 10 , 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 micro-valve 125 provided corresponding to the waste liquid flow channel 135, and a droplet micro-valve 127 provided corresponding to the droplet flow channel 139. The waste liquid flow channel 135, the droplet flow channel 139, the waste liquid micro-valve 125 and the corresponding droplet flow channel 139 can all be understood with reference to the foregoing embodiments. When the second micro-valve 122 and the waste liquid micro-valve 125 are in the open state and the droplet micro-valve 127 is in the closed state, the second liquid in the second flow channel 132 can flow out through the pairing flow channel 136, the oil liquid flow channel 133 and the waste liquid flow channel 135. The discharging process of the second liquid can be understood with reference to the first liquid and will not be elaborated here.

[0158] Based on the second embodiment, referring to Figure 10, in some embodiments of the present utility model, the waste liquid flow channel 135, the droplet flow channel 139, the waste liquid micro valve 125 provided corresponding to the waste liquid flow channel 135, and the droplet micro valve 127 provided corresponding to the droplet flow channel 139 can all be understood with reference to the foregoing embodiments. In this embodiment, when droplets are formed in the oil liquid in the oil liquid flow channel 133, the waste liquid micro valve 125 is in a closed state, and the droplet micro valve 127 is in an open state, so that the droplets are discharged through the droplet flow channel 139. Combining with the foregoing embodiments, by switching the waste liquid micro valve 125 and the droplet flow channel 139, the switching between discharging waste liquid and discharging droplets can be achieved.

[0159] Based on the second embodiment, with reference to Figure 10 , in some embodiments of the present utility model, the microfluidic system further includes a waste liquid flow channel 135, a droplet flow channel 139, a waste liquid micro valve 125 provided corresponding to the waste liquid flow channel 135, and a droplet micro valve 127 provided corresponding to the droplet flow channel 139. The paired flow channel 136 is connected to the inlet end of the oil liquid 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 liquid flow channel 133. Specifically, Figure 10 in the embodiment shown, the paired flow channel 136 is connected to the upper end of the oil liquid 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 liquid 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 paired flow channel 136. The end of the buffer liquid flow channel 134 has two branch flow channels, and the two branch flow channels 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 sent into the paired flow channel 136 approximately synchronously through the buffer liquid.

[0160] Based on the second embodiment, with reference to Figure 10 , in some embodiments of the present utility model, the microfluidic system further includes an oil liquid micro valve 123 provided corresponding to the oil liquid flow channel 133. When discharging waste liquid, the oil liquid micro valve 123 is in a closed state, and the waste liquid can enter the waste liquid flow channel 135 through the oil liquid flow channel 133. When encapsulating, the oil liquid micro valve 123 is in an open state, and the oil liquid flow channel 133 will be filled with oil liquid.

[0161] Based on the second embodiment, with reference to Figure 10, in some embodiments of the present utility model, the microfluidic system further includes a detection module, which is configured to identify a single first target in the first flow channel 131. Wherein, after the detection module identifies a single first target, the first micro-valve 121 is in a closed state to keep the single first target within the first part 1311. It should be noted that in this embodiment, the first micro-valve 121 being in a closed state specifically means switching from an open state to a closed state.

[0162] In some other embodiments, the detection module is configured to identify a single second target in the second flow channel 132. Wherein, after the detection module identifies a single second target, the second micro-valve 122 is in a closed state to keep the single second target within the second part 1321. It should be noted that in this embodiment, the second micro-valve 122 being in a closed state specifically means switching from an open state to a closed state.

[0163] When identifying a single first target A through the detection module, in some embodiments of the present utility model, the microfluidic system further includes a waste liquid micro-valve 125 provided corresponding to the waste liquid flow channel 135, and the waste liquid micro-valve 125 is used to control the on-off of the waste liquid flow channel 135. Wherein, when the detection module does not identify a single first target A, the droplet micro-valve 127 is in a closed state and the first micro-valve 121 and the waste liquid micro-valve 125 are in open states, so that the liquid in the first flow channel 131 can flow out through the pairing flow channel 136, the oil liquid flow channel 133 and the waste liquid flow channel 135. It should be noted that in this embodiment, the droplet micro-valve 127 being in a closed state specifically means remaining in the closed state, and the first micro-valve 121 and the waste liquid micro-valve 125 being in open states specifically means remaining in the open states.

[0164] When identifying a single second target B through the detection module, in some embodiments of the present utility model, when the detection module does not identify a single second target B, the droplet micro-valve 127 is in a closed state and the second micro-valve 122 and the waste liquid micro-valve 125 are in open states, so that the liquid in the second flow channel 132 can flow out through the pairing flow channel 136, the oil liquid flow channel 133 and the waste liquid flow channel 135. It should be noted that in this embodiment, the droplet micro-valve 127 being in a closed state specifically means remaining in the closed state, and the second micro-valve 122 and the waste liquid micro-valve 125 being in open states specifically means remaining in the open states.

[0165] The different detection methods of the detection module can be understood with reference to the visual detection, fluorescence detection and electrode detection in the first embodiment, and will not be elaborated here.

[0166] The embodiments of the present utility model have been described in detail above in conjunction with the accompanying drawings. However, the present utility model is not limited to the above embodiments, and various changes can be made without departing from the gist of the present utility model within the scope of knowledge possessed by those of ordinary skill in the relevant art. In addition, the embodiments of the present utility model and the features in the embodiments can be combined with each other without conflict.

Claims

1. A microfluidic system for object pairing, characterized in that, The microfluidic system includes a first flow channel, a second flow channel, an oil flow channel, a buffer solution flow channel, and a pairing flow channel. The pairing flow channel is connected to the oil flow channel, and the first flow channel, the second flow channel, and the buffer solution flow channel are all connected to the pairing flow channel; The microfluidic system further includes a pairing microvalve provided corresponding to the pairing 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 solution microvalve provided corresponding to the buffer solution flow channel. The pairing microvalve is used to control the on-off of the pairing 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 solution microvalve is used to control the on-off of the buffer solution flow channel; Wherein, when there is a single first target and a single second target 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 the buffer solution in the buffer solution flow channel sends the single first target and the single second target in the pairing 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 includes a waste liquid flow channel and a waste liquid microvalve provided corresponding to the waste liquid flow channel. The waste liquid flow channel is connected to the pairing flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; Wherein, when the pairing 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 pairing flow channel and the waste liquid flow channel; And / or, when the pairing 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 pairing flow channel and the waste liquid flow channel.

3. The microfluidic system for target pairing according to claim 2, wherein The first flow channel, the second flow channel, the buffer solution flow channel, and the waste liquid flow channel are all located on the side of the pairing 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 pairing flow channel, and the waste liquid flow channel is located on the other side of the pairing flow channel.

5. The microfluidic system for target pairing according to claim 2, wherein The microfluidic system further includes at least one of the following solutions: At least a first part of the first flow channel that is connected to the pairing flow channel intersects with the pairing flow channel; At least a second part of the second flow channel that is connected to the pairing flow channel intersects with the pairing flow channel; At least a third part of the waste liquid flow channel that is connected to the pairing flow channel intersects with the pairing flow channel.

6. The microfluidic system for target pairing according to claim 2, wherein At least a fourth part of the buffer solution flow channel that is connected to the pairing flow channel is coaxially arranged with the pairing flow channel.

7. The microfluidic system for target pairing according to claim 2, wherein Along the extending direction of the pairing 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, wherein The microfluidic system further includes a detection module configured to identify a single first target in the first flow channel. Wherein, when the detection module identifies a single first target, the first microvalve and the pairing microvalve are both in a closed state to keep the single first target in the pairing flow channel; And / or, the microfluidic system further includes a detection module configured to identify a single second target in the second flow channel. Wherein, after the detection module identifies a single second target, both the second micro-valve and the paired micro-valve are in a closed state to hold the single second target in the paired flow channel.

9. The microfluidic system for target pairing according to claim 8, wherein, The microfluidic system further includes a waste liquid flow channel and a waste liquid micro-valve provided 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, the paired micro-valve is in a closed state and the first micro-valve and the waste liquid micro-valve 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, the paired micro-valve is in a closed state and the second micro-valve and the waste liquid micro-valve 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 configured to control the camera to capture an image; Wherein, the image at least includes a first image of a first part where the first flow channel communicates with the paired flow channel, and the controller is further configured to identify the single first target based on the first image; And / or, the image at least includes a second image of a second part where the second flow channel communicates with the paired flow channel, and the controller is further configured to identify the single second target based on the second image.

11. The microfluidic system for target pairing according to claim 10, characterized in that, The image at least includes a third image of the paired flow channel, and the controller is configured to identify whether the single first target and / or the single second target 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 configured to control the first light source to emit a first detection light to the first flow channel. The first detection light can excite a first fluorescence after irradiating the single first target, and when the first light detection device detects the first fluorescence, the detection device identifies the single first target; And / or, the detection module includes a second light source, a second light detection device and a controller 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, and when the second light detection device detects the second fluorescence, the controller identifies the single second target.

13. The microfluidic system for target pairing according to claim 8, wherein, The detection module includes a first detection electrode extending into the first flow channel, and the controller is configured to identify the single first target based on the signal detected by the first detection electrode; 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 the signal detected by the second detection electrode.

14. The microfluidic system for target pairing according to claim 8, wherein After the detection module identifies the single first target, the first microvalve switches from the open state to the closed state after a set delay time, so that the single first target enters the pairing flow channel from the first flow channel. And / or, after the detection module identifies the single second target, the second microvalve switches from the open state to the closed state after a set delay time, so that the single second target enters the pairing flow channel from the second flow channel.

15. The microfluidic system for target pairing according to claim 1, wherein The microfluidic system further includes a liquid injection flow channel, which is communicated with the oil flow channel. Define the communication part between the pairing flow channel and the oil flow channel as the first communication part, and the communication part between the liquid injection flow channel and the oil flow channel as the second communication part. The second communication part is located downstream of the first communication part along the flow direction of the oil in the oil flow channel. The microfluidic system further includes a fusion electrode, which is used to apply an electric field to the second communication part to fuse the liquid in the liquid injection flow channel to the droplet flowing through the second communication part.

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 solution flow channel, the pairing flow channel and the liquid injection flow channel are all located in the processing area. Among them, 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, wherein, Both ends of the first electrode are arranged in parallel with the second electrode, and the second electrode is arranged between both ends of the first electrode.

18. The microfluidic system for target pairing according to claim 1, characterized in that, The microfluidic system further includes an oil microvalve 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 includes a first microvalve control flow channel. The first microvalve includes a diaphragm arranged between the first flow channel and the first microvalve control flow channel, and the diaphragm can be driven to protrude towards the first flow channel to be in the closed state. Among them, 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 includes a microfluidic chip, and the microfluidic chip includes a base layer, a control layer and a flow channel layer which are stacked in sequence. Among them, the first flow channel, the second flow channel, the oil flow channel, the buffer solution flow channel and the pairing flow channel are arranged in the flow channel layer. The control layer has the pairing microvalve, the first microvalve, the second microvalve and the buffer solution microvalve.

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

22. The microfluidic system for target pairing according to claim 21, wherein The microsphere is a magnetic microsphere.

23. The microfluidic system for target pairing according to claim 22, characterized in that, The microsphere is a fluorescent magnetic microsphere.

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 includes a first flow channel, a second flow channel, an oil flow channel, a buffer solution flow channel, and a pairing flow channel. The pairing flow channel is connected to the oil flow channel. Both the first flow channel and the second flow channel are connected to the pairing flow channel. The buffer solution 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 pairing flow channel, and the second flow channel has a second part connected to the pairing flow channel. The microfluidic system further includes a first microvalve corresponding to the first flow channel, a second microvalve corresponding to the second flow channel, and a buffer solution microvalve corresponding to the buffer solution 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 solution microvalve is used to control the on / off of the buffer solution flow channel. Wherein, when there is a single first target in the first part and a single second target in the second part, the first microvalve and the second microvalve are in the closed state, and the buffer solution microvalve is in the open state, so that the buffer solution in the buffer solution flow channel sends the single first target in the first part and the single second target in the second part into the oil in the oil flow channel through the pairing flow channel to form droplets.

26. The microfluidic system for target pairing according to claim 25, characterized in that, 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. 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 the open state and the droplet microvalve is in the closed state, the liquid in the first flow channel can flow out through the pairing 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 the open state and the droplet microvalve is in the closed state, the liquid in the second flow channel can flow out through the pairing flow channel, the oil flow channel, and the waste liquid flow channel.

27. The microfluidic system for target pairing according to claim 25, wherein 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. 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 droplets are formed in the oil in the oil flow channel, the waste liquid microvalve is in the closed state and the droplet microvalve is in the 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 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. 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. Among them, the paired flow channel is connected to the inlet end of the oil flow channel, and both the waste liquid flow channel and the droplet flow channel are 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 configured to identify a single first target in the first flow channel. Wherein, after the detection module identifies a single first target, the first micro-valve is in a closed state to keep the single first target in the first part. And / or, the microfluidic system further includes a detection module configured to identify a single second target in the second flow channel. Wherein, after the detection module identifies a single second target, the second micro-valve is in a closed state to keep the single second target in the second part.

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