Microfluidic system for target object pairing

Abstract

The invention 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, 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. The first flow channel comprises a first flow section different from the first micro-valve, the second flow channel comprises a second flow section different from the second micro-valve, and the upper side inner wall surfaces and the lower side inner wall surfaces of the first flow section and the second flow channel are parallel planes, so that the distance difference between different target objects and the upper side inner wall surfaces is reduced; therefore, the flow velocity difference caused by the distance difference is reduced, the stopping range of the target object is further reduced, the pressure of the buffer solution and the volume of the liquid can be correspondingly reduced, and the capturing success rate can be improved.

Description

Technical Field

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

[0002] Single-cell RNA sequencing technology (scRNA-seq) reveals the heterogeneity of cells in tissues. Compared with traditional gene sequencing technology, single-cell sequencing technology has the advantages of high precision and high resolution, can provide information at the single-cell level, reveal the heterogeneity and complexity of expression in tissues, and has wide applications in cancer, reproduction, immunity and development. Compared with traditional sequencing, single-cell sequencing requires the separation of cell groups in tissues or body fluids into single cells. At present, there is a cell pairing system, which is provided with a cell flow channel, a microsphere flow channel, a pairing flow channel, a buffer flow channel, an oil flow channel, a detection module and a corresponding control microvalve. A first liquid containing cells flows in the cell flow channel, and a second liquid containing microspheres flows in the microsphere flow channel. When the detection module detects cells or microspheres, the corresponding microvalve is controlled to close the flow channel at a certain interval, so that a single cell and a single microsphere can stop in the pairing flow channel, and then the buffer in a separate buffer flow channel pushes the single cell and the single microsphere into the oil in the oil flow channel to be encapsulated into droplets.

[0003] However, this cell pairing system has the following drawbacks: 1. Due to the cross-sectional shape of the cell flow channel or the microsphere flow channel, different cells or different microspheres may have different flow velocities when flowing in the flow channel with liquid as the carrier. Taking cells as an example, some cells are relatively close to the flow channel wall in the flow channel, and their movement speed is relatively slow, while some cells are relatively far away from the flow channel wall in the flow channel, and their movement speed is relatively fast. The interval time from the detection module detecting the cell to the microvalve shutoff is fixed, and the interval time from the detection module detecting the cell to the control microvalve shutoff is fixed, which increases the interception range of different cells. In order to compensate for this factor, it is necessary to increase the buffer pressure used to flush the cells. However, this will increase the particle size of the droplets after pairing, reducing the probability of collision between the mRNA released by the cells and the microspheres, affecting the capture of the cell mRNA by the microspheres.

[0004] 2. Cells or microspheres that have entered the paired flow channel are easily affected by liquid flow and there is a risk of being washed out of the paired flow channel by the liquid. Taking cells as an example, when a single cell enters the paired flow channel but the microsphere has not yet entered, the liquid in the microsphere flow channel needs to continue to flow and pass through the paired space. The disturbance of the liquid may wash away the single cell in the paired space, resulting in only microspheres in the encapsulated droplets.

[0005] 3. The encapsulated droplets are likely to come into large-area contact with the wall of the oil channel, and the droplets are easily broken under the wetting effect. Summary of the invention

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

[0007] According to the microfluidic system for target pairing in the first embodiment of the present invention, the microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a pairing flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the pairing flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; The first flow channel includes a first microvalve section corresponding to the first microvalve and a first flow section different from the first microvalve section, and the upper inner wall surface and the lower inner wall surface of the first flow section are parallel planes to each other; And / or, the second flow channel includes a second microvalve section corresponding to the second microvalve, and a second flow section different from the second microvalve section, and the upper inner wall surface and the lower inner wall surface of the second flow section are planes parallel to each other.

[0008] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects: This embodiment reduces the distance difference between different targets and the upper inner wall surface by setting the upper inner wall surface and the lower inner wall surface of the first flow section to be parallel planes, thereby reducing the flow velocity difference caused by this distance difference, and further narrowing the interception range of the target object. Therefore, the pressure of the buffer solution and the volume of the liquid can be reduced accordingly, which helps to improve the success rate of capture.

[0009] In other embodiments of the present invention, the cross-section of the first flow segment is set to be a rectangle, and / or the cross-section of the second flow segment is set to be a rectangle.

[0010] In other embodiments of the present invention, the width of the first flow segment is 50 microns to 150 microns, and / or the width of the second flow segment is 50 microns to 150 microns.

[0011] In other embodiments of the present invention, the upper inner wall surface of the first microvalve section is set as a curved surface convex away from the first microvalve, and / or the upper inner wall surface of the second microvalve section is set as a curved surface convex away from the second microvalve.

[0012] In other embodiments of the present invention, the cross-section of the first microvalve section is set to be semicircular, and / or the cross-section of the second microvalve section is set to be semicircular.

[0013] In other embodiments of the present invention, the maximum height of the oil flow channel is 80 microns to 200 microns.

[0014] In other embodiments of the present invention, the microfluidic system further comprises a first sheath liquid flow channel, the first sheath liquid flow channel being in communication with the first flow channel and being used for inputting a first sheath flow enveloping the first liquid into the first flow channel; And / or, the microfluidic system further comprises a second sheath liquid flow channel, wherein the second sheath liquid flow channel is connected to the second flow channel and is used for inputting a second sheath flow enveloping the second liquid into the second flow channel.

[0015] In other embodiments of the present invention, the microfluidic system further comprises a waste liquid flow channel and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, the waste liquid flow channel is communicated with the paired flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; Wherein, when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

[0016] In other embodiments of the present invention, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a first stop microvalve, which is used to control the opening and closing of the paired flow channel located between the waste liquid flow channel and the first flow channel.

[0017] In other embodiments of the present invention, the microfluidic system is configured as follows: when the single first target is located in the pairing flow channel, the first shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the first shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

[0018] In other embodiments of the present invention, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a second stop microvalve, which is used to control the on-off of the paired flow channel located between the waste liquid flow channel and the second flow channel.

[0019] In other embodiments of the present invention, the microfluidic system is configured as follows: when the single second target is located in the pairing flow channel, the second shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the second shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

[0020] In other embodiments of the present invention, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are arranged in sequence, and the microfluidic system is configured such that: after the single first target object is located in the paired flow channel, the second microvalve is again in a closed state so that the single second target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the first flow channel and the second flow channel are sequentially arranged, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is again in a closed state so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the second flow channel, the first flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is in a closed state again so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured as follows: when the single first target object is located in the paired flow channel, the second microvalve is closed again to allow the single second target object to be located in the paired flow channel.

[0021] According to the microfluidic system for target pairing in the second embodiment of the present invention, the microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a pairing flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the pairing flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, the maximum height of the oil flow channel is 80 microns to 200 microns.

[0022] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects: This embodiment can reduce the probability of droplets contacting the flow channel wall of the oil flow channel by setting the maximum height of the oil flow channel, thereby reducing the risk of droplets breaking.

[0023] In other embodiments of the present invention, the upper inner wall surface and the lower inner wall surface of the oil flow channel are planes parallel to each other.

[0024] In other embodiments of the present invention, the cross-section of the oil flow channel is set to be rectangular.

[0025] According to the microfluidic system for target pairing in the third embodiment of the present invention, the microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a pairing flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the pairing flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, the microfluidic system further comprises a first sheath liquid flow channel, the first sheath liquid flow channel being in communication with the first flow channel and being used for inputting a first sheath flow enveloping the first liquid into the first flow channel; And / or, the microfluidic system further comprises a second sheath liquid flow channel, wherein the second sheath liquid flow channel is connected to the second flow channel and is used for inputting a second sheath flow enveloping the second liquid into the second flow channel.

[0026] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects: In this embodiment, by setting a sheath liquid to constrain the first liquid and / or the second liquid, the first liquid and / or the second liquid can flow in the central area of ​​the flow channel, thereby preventing the first target object in the first liquid and / or the target object in the second liquid from being too close to the inner wall surface of the flow channel, thereby preventing a large flow rate difference from occurring.

[0027] In other embodiments of the present invention, the first sheath fluid flow channel includes two first branch flow channels, and the two first branch flow channels are respectively connected to the first flow channel from both sides of the first flow channel; And / or, the second sheath fluid flow channel includes two second branch flow channels, and the two second branch flow channels are respectively connected to the second flow channel from both sides of the second flow channel.

[0028] According to the microfluidic system for target pairing in the fourth embodiment of the present invention, the microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a pairing flow channel and a waste flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all connected to the pairing flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, a buffer solution microvalve arranged corresponding to the buffer solution flow channel, and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, the buffer solution microvalve is used to control the on-off of the buffer solution flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Among them, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a first stop microvalve, which is used to control the opening and closing of the paired flow channel located between the waste liquid flow channel and the first flow channel.

[0029] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects: By providing the first stop microvalve, this embodiment can prevent the first target object that has entered the matching flow channel from being driven out of the matching flow channel by the second liquid, resulting in only the second target object in the encapsulated droplet, thereby ensuring the encapsulation success rate.

[0030] In other embodiments of the present invention, the microfluidic system is configured as follows: when the single first target is located in the pairing flow channel, the first shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the first shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

[0031] In other embodiments of the present invention, when the single first target does not exist in the paired flow channel, the paired microvalve is in a closed state and the first microvalve, the first stop microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the single second target object does not exist in the paired flow channel, the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

[0032] According to the microfluidic system for target pairing in the fifth embodiment of the present invention, the microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a pairing flow channel and a waste flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all connected to the pairing flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, a buffer solution microvalve arranged corresponding to the buffer solution flow channel, and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, the buffer solution microvalve is used to control the on-off of the buffer solution flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Among them, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a second stop microvalve, which is used to control the on-off of the paired flow channel located between the waste liquid flow channel and the second flow channel.

[0033] The microfluidic system for target pairing according to the embodiment of the present invention has at least the following beneficial effects: This embodiment provides a second stop microvalve to prevent the second target object that has entered the paired flow channel from being driven out of the paired flow channel by the first liquid, resulting in only the first target object in the encapsulated droplet, thereby ensuring the encapsulation success rate.

[0034] In other embodiments of the present invention, the microfluidic system is configured as follows: when the single second target is located in the pairing flow channel, the second shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the second shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

[0035] In other embodiments of the present invention, when the single first target does not exist in the paired flow channel, the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the single second target object does not exist in the paired flow channel, the paired microvalve is in a closed state and the second microvalve, the second stop microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

[0036] According to the microfluidic system for target pairing in the sixth embodiment of the present invention, the microfluidic system includes a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a pairing flow channel and a waste flow channel, the pairing flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all connected to the pairing flow channel, and the waste flow channel is located between the first flow channel and the second flow channel, the first flow channel is used for passing a first liquid containing a first target, and the second flow channel is used for passing a second liquid containing a second target ; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, a buffer solution microvalve arranged corresponding to the buffer solution flow channel, and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, the buffer solution microvalve is used to control the on-off of the buffer solution flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are arranged in sequence, and the microfluidic system is configured such that: after the single first target object is located in the paired flow channel, the second microvalve is in a closed state again to allow the single second target object to be located in the paired flow channel. Wherein, since the waste liquid flow channel is arranged on a side close to the second flow channel, the second liquid will flow toward the waste liquid flow channel instead of toward the first flow channel that has been cut off, thereby preventing the single first target object A from being carried away by the second liquid.

[0037] Alternatively, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the first flow channel and the second flow channel are arranged in sequence, and the microfluidic system is configured such that: after the single second target object is located in the paired flow channel, the first microvalve is in a closed state again to allow the single first target object to be located in the paired flow channel. Among them, since the waste liquid flow channel is arranged on the side close to the first flow channel, the first liquid will flow toward the waste liquid flow channel instead of the cut-off second flow channel, thereby preventing the single second target object B from being carried away by the first liquid.

[0038] Alternatively, along the flow direction of the buffer in the paired flow channel, the second flow channel, the first flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured such that: after the single second target object is located in the paired flow channel, the first microvalve is in a closed state again to allow the single first target object to be located in the paired flow channel. Since the waste liquid flow channel is arranged on a side close to the first flow channel, the first liquid will flow toward the waste liquid flow channel instead of toward the cut-off second flow channel, thereby preventing the single second target object B from being carried away by the first liquid.

[0039] Alternatively, along the flow direction of the buffer in the paired flow channel, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured such that: after the single first target is located in the paired flow channel, the second microvalve is in a closed state again to allow the single second target to be located in the paired flow channel. Since the waste liquid flow channel is arranged on a side close to the second flow channel, the second liquid will flow toward the waste liquid flow channel instead of toward the first flow channel that has been cut off, thereby preventing the single first target A from being carried away by the second liquid.

[0040] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The present invention will be further described below in conjunction with the accompanying drawings and embodiments, wherein: Figure 1 A schematic diagram of a microfluidic system in a first embodiment of the present invention; Figure 2 for Figure 1 Schematic diagram showing an enlarged view of the paired flow channels; Figure 3 A schematic diagram of a process of pairing a first target object with a second target object by a microfluidic system in the first embodiment of the present invention; Figure 4 This is an exploded schematic diagram of a microfluidic chip in the first embodiment of the present invention; Figure 5 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 Figure 6 is a schematic cross-sectional view of a first flow channel section in a first embodiment of the present invention; Figure 7 A schematic diagram showing the relative position relationship among the first flow channel, the second flow channel, the waste liquid flow channel and the first stop microvalve in the fifth embodiment of the present invention; Figure 8 A schematic diagram showing the relative position relationship among the first flow channel, the second flow channel and the waste liquid flow channel in the sixth embodiment of the present invention; Fig. 9 A schematic diagram showing the relative position relationship among the first flow channel, the second flow channel and the waste liquid flow channel in the seventh embodiment of the present invention; Fig.10 A schematic diagram showing the relative position relationship among the first flow channel, the second flow channel and the waste liquid flow channel in the eighth embodiment of the present invention; Fig.11 It is a schematic diagram showing the relative position relationship among the first flow channel, the second flow channel and the waste liquid flow channel in the ninth embodiment of the present invention.

[0042] Reference numerals: Microfluidic chip 100, base layer 110, control layer 120, first microvalve 121, diaphragm 1211, second microvalve 122, oil microvalve 123, buffer microvalve 124, waste liquid microvalve 125, matching microvalve 126, first stop microvalve 127, second stop microvalve 128, channel layer 130, first channel 131, first microvalve section 1311, first flow section 1312, second channel 132, second microvalve section 1321, second flow section 1322, oil channel 133, buffer channel 134, fourth portion 1341, waste liquid channel 135, matching channel 136, first sheath liquid channel 137, first branch channel 1371, second sheath liquid channel 138, second branch channel 1381, first microvalve control channel 139; A single first target object A; A single second target object B; Droplet C; The first detection light D Second detection light E. DETAILED DESCRIPTION

[0043] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0044] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., and orientations or positional relationships indicated are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0045] In the description of the present invention, "several" means more than one, "many" means more than two, "greater than", "less than", "exceed", etc. are understood to exclude the number itself, and "above", "below", "within", etc. are understood to include the number itself. If there is a description of "first" or "second", it is only used for the purpose of distinguishing the technical features, and cannot be understood as indicating or implying the relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0046] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, connecting, etc. should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention in combination with the specific content of the technical solution.

[0047] In the description of the present invention, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0048] The first embodiment of the present invention provides a microfluidic system for target pairing, referring to Figures 1 to 3, including a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134 and a matching flow channel 136, wherein the first flow channel 131 is used for passing a first liquid containing a first target, the second flow channel 132 is used for passing a second liquid containing a second target, the buffer flow channel 134 is used for passing a buffer, the oil flow channel 133 is used for passing an oil that is not soluble in the first liquid, the second liquid and the buffer, and the matching flow channel 136 is used for allowing a single first target A and a single second target B to stay. The matching flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132 and the buffer flow channel 134 are all connected to the matching flow channel 136. In this embodiment, the first target is a cell and the second target is a microsphere for description. It can be understood by those skilled in the art that the first target can be a cell and the second target can also be a cell.

[0049] The microfluidic system of the present embodiment further includes a plurality of microvalves, specifically including a paired microvalve 126 arranged corresponding to the paired flow channel 136, a first microvalve 121 arranged corresponding to the first flow channel 131, a second microvalve 122 arranged corresponding to the second flow channel 132, and a buffer solution microvalve 124 arranged corresponding to the buffer solution flow channel 134, wherein the paired microvalve 126 is used to control the on-off of the paired flow channel 136, the first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer solution microvalve 124 is used to control the on-off of the second flow channel 132. 124 is used to control the on-off of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the on-off of the first flow channel 131 of the first microvalve 121 controller means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a 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.

[0050] For ease of understanding, please refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are explained, such as Figure 4As shown, the microfluidic system includes a microfluidic chip 100, and the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 which are stacked in sequence. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS). Among them, the flow channel layer 130 has the aforementioned first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste liquid flow channel 135 and the matching flow channel 136. The control layer 120 has the aforementioned first microvalve 121, the second microvalve 122, the buffer microvalve 124, the waste liquid microvalve 125 and the matching microvalve 126, as well as microvalve control flow channels corresponding to each microvalve. Refer to Figure 5 Taking the first microvalve 121 as an example, the first microvalve 121 includes a diaphragm 1211 disposed between the first flow channel 131 (specifically, the first microvalve section 1311 described below) and the first microvalve control flow channel 139. When the first microvalve 121 is in a state as Figure 5 In the open state shown in a in FIG. 1 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first microvalve section 1311; when the diaphragm 1211 is driven by the liquid or gas in the first microvalve control channel 139 and protrudes toward the first channel 131 to be in a state as shown in FIG. Figure 5 In the closed state shown in b in FIG. 1 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first microvalve section 1311, and the first liquid cannot pass through the first microvalve section 1311. Figure 5 In the embodiment shown, the upper inner wall surface of the first microvalve segment 1311 is set as an arc surface protruding away from the first microvalve 121, specifically a semicircular arc surface, which is convenient for fitting with the diaphragm 1211 protruding toward the first microvalve segment 1311, thereby ensuring the cutoff effect. The second microvalve segment 1321 of the second flow channel 132 can be understood with reference to the first microvalve segment 1311.

[0051] In this embodiment, refer to Figure 3From step c to step d, 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 a closed state (the microvalve is filled in black to indicate that it is in a closed state), and the paired microvalve 126 and the buffer microvalve 124 are in an open state (the microvalve is filled in gray to indicate that it is in an open state), at this time, the buffer in the buffer flow channel 134 can deliver 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. In this way, through the single paired The flow channel 136 is used to temporarily store a single first target object A and a single second target object B, and is provided with a separate buffer flow channel 134. The single first target object A and the single second target object B are pushed into the oil by the buffer, and there is no need to push the single first target object A and the single second target object B by the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0052] On this basis, refer to Figure 1 , the first flow channel 131 includes a first microvalve section 1311 corresponding to the first microvalve 121, and a first flow section 1312 different from the first microvalve section 1311, wherein the first flow section 1312 mainly serves the function of allowing the first liquid to flow, and the first microvalve section 1311, in addition to serving the function of allowing the first liquid to flow, also serves the function of cooperating with the first microvalve 121 to achieve shutoff control. Exemplarily, when observed from a direction perpendicular to the microfluidic chip 100, the first microvalve section 1311 covers the first microvalve 121, and along the flow direction of the first liquid, the upstream (the part connected to the inlet of the first liquid) and the downstream (the part connected to the matching flow channel 136) of the first microvalve section 1311 are both the first flow section 1312. In this embodiment, there is a difference in the cross-sectional shape of the first microvalve section 1311 and the first flow section 1312, and the first microvalve section 1311 can be set as follows Figure 5 The flow passage with the curved upper wall shown in FIG. Figure 6 As shown, the upper inner wall surface and the lower inner wall surface are parallel planes. The purpose of this design is: if the first flow section 1312 adopts Figure 5In the flow channel with an arc-shaped upper wall shown in the figure, different cells or different microspheres may have different flow velocities when flowing in the flow channel with liquid as a carrier. Taking cells as an example, some cells are located in the center of the flow channel, and they are far away from the upper wall, and the flow speed is relatively fast. Some cells are located on the side of the flow channel, and they are close to the upper wall, and the movement speed is relatively slow. The interval time from the detection module detecting the cell to the control microvalve shutoff is fixed, which increases the interception range of different cells in the paired flow channel 136. In order to ensure that the cells stopped at different positions can be filled into the oil flow channel 133. It is necessary to increase the pressure of the buffer used to flush the cells. However, this will increase the particle size of the droplets after pairing, which reduces the probability of collision between the mRNA released by the cells and the microspheres, affecting the capture of the cell mRNA by the microspheres. In this embodiment, the upper inner wall surface and the lower inner wall surface are parallel to each other, thereby reducing the distance difference between different cells and the upper inner wall surface, thereby reducing the flow rate difference caused by this distance difference, and further reducing the cell interception range. The pressure of the buffer solution and the volume of the liquid can be reduced accordingly, which helps to improve the success rate of capture.

[0053] In other embodiments, the second flow channel 132 includes a second microvalve section 1321 corresponding to the second microvalve 122, and a second flow section 1322 different from the second microvalve section 1321, and the upper inner wall surface and the lower inner wall surface of the second flow section 1322 are planes parallel to each other. The structure and function of the second microvalve section 1321 and the second flow section 1322 of this embodiment can be understood with reference to the first microvalve section 1311 and the first flow section 1312.

[0054] Based on the first embodiment, in some embodiments of the present invention, referring to Figure 6 The cross section of the first flow section 1312 is set to be rectangular, which can reduce the difficulty of preparing the flow channel while ensuring that the upper inner wall surface and the lower inner wall surface of the first flow section 1312 are parallel to each other.

[0055] In other embodiments, the cross-section of the second flow segment 1322 is set to be rectangular, which can reduce the difficulty of preparing the flow channel while ensuring that the upper inner wall surface and the lower inner wall surface of the second flow segment 1322 are parallel to each other.

[0056] On the basis of the first embodiment, in some embodiments of the present invention, the width of the first flow segment 1312 is 50 microns to 150 microns, that is, the first flow segment 1312 has enough space in the width direction, which can prevent the first target from being too close to the left and right inner sides of the first flow segment 1312 to affect the flow rate, thereby reducing the flow rate difference caused by this distance difference between different first targets, thereby further improving the success rate of pairing. Exemplarily, the width of the first flow segment 1312 is 50 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns and 150 microns.

[0057] In other embodiments, the width of the second flow segment 1322 is 50 microns to 150 microns, that is, the second flow segment 1322 has enough space in the width direction, which can prevent the second target from being too close to the left and right inner sides of the second flow segment 1322 to affect the flow rate, thereby reducing the flow rate difference between different second targets due to this distance difference, thereby further improving the success rate of pairing. Exemplarily, the width of the second flow segment 1322 is 50 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns and 150 microns.

[0058] On the basis of the first embodiment, in some embodiments of the present invention, the maximum height of the oil flow channel 133 is 80 microns to 200 microns. In the actual packaging process, the encapsulated droplets may have a large-area contact with the flow channel wall of the oil flow channel 133, causing the droplets to adhere to the flow channel wall and be broken as the oil flows. By setting the maximum height of the oil flow channel 133, this embodiment can reduce the probability of the droplets contacting the flow channel wall of the oil flow channel 133, thereby reducing the risk of droplet breakage. Exemplarily, the maximum height of the oil flow channel 133 is 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns, 150 microns, 160 microns, 170 microns, 180 microns, 190 microns and 200 microns.

[0059] In some specific embodiments, the upper inner wall surface of the oil flow channel 133 can be an arc surface similar to the first microvalve section 1311, or a plane similar to the first flow section 1312. When it is an arc surface, the maximum height of the oil flow channel 133 is the height of the vertex of the arc surface.

[0060] Based on the first embodiment, in some embodiments of the present invention, referring to Figure 1The microfluidic system also includes a first sheath liquid flow channel 137, which is connected to the first flow channel 131 and is used to input a first sheath flow that wraps the first liquid into the first flow channel 131. In this embodiment, by setting a sheath liquid to constrain the first liquid, the first liquid can flow in the central area of ​​the flow channel to prevent the first target object in the first liquid from being too close to the inner wall surface of the flow channel. It should be noted that this embodiment, combined with the aforementioned setting of the upper and lower inner wall surfaces of the first flow section 1312 as mutually parallel planes, can further ensure that the flow rate of different first targets remains stable.

[0061] In some specific embodiments, referring to Figure 1 The first sheath liquid flow channel 137 includes two first branch flow channels 1371 , and the two first branch flow channels 1371 are connected to the first flow channel 131 from both sides of the first flow channel 131 , so that the first liquid can be confined between the two sheath flows.

[0062] In other embodiments, reference Figure 1 The microfluidic system also includes a second sheath liquid flow channel 138, which is connected to the second flow channel 132 and is used to input a second sheath flow that wraps the second liquid into the second flow channel 132. In this embodiment, by setting the sheath liquid to constrain the second liquid, the second liquid can flow in the central area of ​​the flow channel to prevent the second target object in the second liquid from being too close to the inner wall surface of the flow channel. It should be noted that this embodiment, combined with the above-mentioned setting of the upper and lower inner wall surfaces of the second flow section 1322 as mutually parallel planes, can further ensure that the flow rate of different second targets remains stable.

[0063] In some specific embodiments, referring to Figure 1 The second sheath liquid flow channel 138 includes two second branch flow channels 1381 , and the two second branch flow channels 1381 are respectively connected to the second flow channel 132 from both sides of the second flow channel 132 , so that the second liquid can be confined between the two sheath flows.

[0064] Based on the first embodiment, refer to Figures 1 to 3In some embodiments of the present invention, the microfluidic system further includes a waste liquid flow channel 135, the waste liquid flow channel 135 is used to discharge the first liquid and the second liquid, and the waste liquid flow channel 135 is connected to the matching flow channel 136. In addition, the microfluidic system further includes a waste liquid microvalve 125 provided corresponding to the waste liquid flow channel 135, and the waste liquid microvalve 125 is used to control the on-off of the waste liquid flow channel 135. When the matching microvalve 126 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, the first liquid in the first flow channel 131 can flow out through the matching flow channel 136 and the waste liquid flow channel 135. In other embodiments, when the matching microvalve 126 is in a closed state and the second microvalve 122 and the waste liquid microvalve 125 are in an open state, the liquid in the second flow channel 132 can flow out through the matching flow channel 136 and the waste liquid flow channel 135. It should be noted that the first target object and the second target object will follow the flow of the first liquid and the second liquid respectively and gradually approach and reach the matching channel 136. When the first target object and the second target object have not yet reached the matching channel 136, the first channel 131 and the second channel 132 will continue to discharge the first liquid and the second liquid, and these first liquids and the second liquids need to be discharged as waste liquids.

[0065] Combined with the above structure, Figures 1 to 3 Describe the control of each microvalve: During the pairing process, the buffer solution microvalve 124 and the paired microvalve 126 are closed, the first microvalve 121, the second microvalve 122 and the waste liquid microvalve 125 are opened, and the first liquid and the second liquid are discharged through the paired flow channel 136 and the waste liquid flow channel 135 (for example, Figure 3 When a single first target is identified, the first microvalve 121 is closed, and the single first target stops in the paired flow channel 136 (for example Figure 3 b). When a single second target is identified, the second microvalve 122 is closed, and the single second target stops in the paired flow channel 136 (for example Figure 3 c). When the single first target object and the single second target object both stop in the paired flow channel 136, the waste liquid micro valve 125 is closed.

[0066] During the packaging process, when the first microvalve 121, the second microvalve 122, and the waste liquid microvalve 125 are closed, the buffer solution microvalve 124 and the matching microvalve 126 are opened, and the buffer solution delivers the single first target object and the single second target object in the matching flow channel 136 into the oil in the oil flow channel 133 to form droplets (for example, Figure 3 d) in.

[0067] When the microfluidic system further includes a waste liquid channel 135, in some embodiments of the present invention, Figure 1 , Figure 2 , along the flow direction of the buffer solution in the paired flow channel 136, for example Figure 1 , Figure 2 From top to bottom, the waste liquid channel 135 is located between the first channel 131 and the second channel 132. On this basis, the microfluidic system further includes a first stop microvalve 127, which is used to control the on-off of the paired channel 136 located between the waste liquid channel 135 and the first channel 131. Figure 1 , Figure 2 From top to bottom, the first stop microvalve 127 is disposed on the matching flow channel 136 between the waste liquid flow channel 135 and the first flow channel 131. By disposing the first stop microvalve 127, the embodiment can prevent the first target object that has entered the matching flow channel 136 from being driven out of the matching flow channel 136 by the second liquid, resulting in only the second target object in the encapsulated droplet, thereby ensuring the encapsulation success rate.

[0068] In some specific embodiments, in combination Figure 1 , Figure 2 It is understood that the microfluidic system is configured as follows: when a single first target object A is located in the matching flow channel 136, the first stop microvalve 127 is switched from an open state to a closed state. At this time, the matching flow channel 136 where the single first target object A is located and the matching flow channel 136 through which the second liquid flows are isolated by the first stop microvalve 127, and the flow of the second liquid will not drive the first target object.

[0069] The microfluidic system is also configured as follows: when there is a single first target A and a single second target B in the pairing flow channel 136, the first microvalve 121, the second microvalve 122 and the waste liquid microvalve 125 are in a closed state, and the pairing microvalve 126, the buffer microvalve 124 and the first stop microvalve 127 are in an open state, so that the buffer in the buffer flow channel 134 can deliver the single first target A and the single second target B in the pairing flow channel 136 into the oil in the oil flow channel 133 to form droplets C.

[0070] In this embodiment, by controlling the on-off of the first stop microvalve 127 , the first target object can be stored in the pairing flow channel 136 during the waiting process for pairing without affecting the pairing and packaging of the first target object and the second target object.

[0071] It should be noted that, before the first stop microvalve 127 is in the closed state, the second microvalve 122 can be in the open state all the time, so that the second liquid is continuously discharged from the waste liquid channel 135 (that is, the second target object B is not captured). The second microvalve 122 can also be in the closed state first, and when the first stop microvalve 127 is in the closed state, the second microvalve 122 is opened again to capture the subsequent single second target object B.

[0072] When the microfluidic system further includes a waste liquid flow channel 135, in some other embodiments of the present invention, Figure 7 , along the flow direction of the buffer solution in the paired flow channel 136, for example Figure 7 From top to bottom in the figure, the waste liquid flow channel 135 is located between the first flow channel 131 and the second flow channel 132. On this basis, the microfluidic system further includes a second stop microvalve 128, which is used to control the on-off of the paired flow channel 136 located between the waste liquid flow channel 135 and the second flow channel 132. Figure 7 From top to bottom, the second stop microvalve 128 is disposed on the matching flow channel 136 between the waste liquid flow channel 135 and the second flow channel 132. By disposing the second stop microvalve 128, the second target object that has entered the matching flow channel 136 can be prevented from being driven out of the matching flow channel 136 by the first liquid, resulting in only the first target object in the encapsulated droplet, thereby ensuring the encapsulation success rate.

[0073] In some specific embodiments, in combination Figure 7 It is understood that the microfluidic system is configured as follows: when a single second target object B is located in the matching flow channel 136, the second stop microvalve 128 is switched from an open state to a closed state. At this time, the matching flow channel 136 where the single second target object B is located and the matching flow channel 136 through which the first liquid flows are isolated by the second stop microvalve 128, and the flow of the first liquid will not drive the second target object.

[0074] The microfluidic system is also configured as follows: when there is a single first target A and a single second target B in the pairing flow channel 136, the first microvalve 121, the second microvalve 122 and the waste liquid microvalve 125 are in a closed state, and the pairing microvalve 126, the buffer microvalve 124 and the second shut-off microvalve 128 are in an open state, so that the buffer in the buffer flow channel 134 can deliver the single first target A and the single second target B in the pairing flow channel 136 into the oil in the oil flow channel 133 to form droplets C.

[0075] In this embodiment, by controlling the on-off of the second stop microvalve 128 , the second object can be stored in the pairing flow channel 136 during the waiting process for pairing without affecting the pairing and packaging of the first object and the second object.

[0076] In other embodiments, the microfluidic system may not be provided with a stop microvalve. Figure 8 , along the flow direction of the buffer solution in the paired flow channel 136, for example Figure 8From top to bottom, the waste liquid channel 135, the second channel 132 and the first channel 131 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single first target A is located in the matching channel 136, the second microvalve 122 is in a closed state again so that the single second target B is located in the matching channel 136, that is, this embodiment needs to first ensure that the single first target A is located in the matching channel 136 (at this time, the first microvalve 121 is already in a closed state), and then the single second target B is located in the matching channel 136. Exemplarily, the second microvalve 122 is in a closed state before the single first target A is located in the matching channel 136, and the second microvalve 122 is opened again after the single first target A is located in the matching channel 136. When the detection module detects the single second target B, the second microvalve 122 is closed again, so that the single second target B can stop in the matching channel 136.

[0077] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the second channel 132, the second liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off first channel 131, thereby preventing a single first target object A from being carried away by the second liquid.

[0078] In other embodiments, referring to Fig. 9 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig. 9 From top to bottom, the waste liquid channel 135, the first channel 131 and the second channel 132 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single second target B is located in the matching channel 136, the first microvalve 121 is in a closed state again so that the single first target A is located in the matching channel 136, that is, this embodiment needs to first ensure that the single second target N is located in the matching channel 136 (at this time, the second microvalve 122 is already in a closed state), and then the single first target A is located in the matching channel 136. Exemplarily, the first microvalve 121 is in a closed state before the single second target B is located in the matching channel 136, and the first microvalve 121 is opened again after the single second target B is located in the matching channel 136. When the detection module detects the single first target A, the first microvalve 121 is closed again, so that the single first target A can stop in the matching channel 136.

[0079] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the first channel 131, the first liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off second channel 132, thereby preventing a single second target object B from being carried away by the first liquid.

[0080] In other embodiments, referring to Fig.10 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig.10 From top to bottom, the second flow channel 132, the first flow channel 131 and the waste liquid flow channel 135 are arranged in sequence. On this basis, the microfluidic system is configured as follows: when the single second target object B is located in the matching flow channel 136, the first microvalve 121 is in a closed state again so that the single first target object A is located in the matching flow channel 136, that is, this embodiment needs to first ensure that the single second target object N is located in the matching flow channel 136 (at this time, the second microvalve 122 is already in a closed state), and then the single first target object A is located in the matching flow channel 136. Exemplarily, the first microvalve 121 is in a closed state before the single second target object B is located in the matching flow channel 136, and the first microvalve 121 is opened again after the single second target object B is located in the matching flow channel 136. When the detection module detects the single first target object A, the first microvalve 121 is closed again, so that the single first target object A can stop in the matching flow channel 136.

[0081] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the first channel 131, the first liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off second channel 132, thereby preventing a single second target object B from being carried away by the first liquid.

[0082] In other embodiments, referring to Fig.11 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig.11 From top to bottom, the first flow channel 131, the second flow channel 132 and the waste liquid flow channel 135 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single first target A is located in the matching flow channel 136, the second microvalve 122 is in a closed state again so that the single second target B is located in the matching flow channel 136, that is, this embodiment needs to first ensure that the single first target A is located in the matching flow channel 136 (at this time, the first microvalve 121 is already in a closed state), and then the single second target B is located in the matching flow channel 136. Exemplarily, the second microvalve 122 is in a closed state before the single first target A is located in the matching flow channel 136, and the second microvalve 122 is opened again after the single first target A is located in the matching flow channel 136. When the detection module detects the single second target B, the second microvalve 122 is closed again, so that the single second target B can stop in the matching flow channel 136.

[0083] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the second channel 132, the second liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off first channel 131, thereby preventing a single first target object A from being carried away by the second liquid.

[0084] On the basis of the first embodiment, the microfluidic system of some embodiments of the present invention further includes a detection module, which is configured to identify a single first target object A in the first flow channel 131, wherein when the detection module identifies the single first target object A, the first microvalve 121 and the paired microvalve 126 are both in a closed state to keep the single first target object A in the paired flow channel 136. It should be noted that, in this embodiment, the first microvalve 121 being in a closed state specifically refers to switching from an open state to a closed state, and the paired microvalve 126 being in a closed state specifically refers to remaining in a closed state.

[0085] In other embodiments, the detection module is configured to identify a single second target object B in the second flow channel 132, wherein, when the detection module identifies the single second target object B, the second microvalve 122 and the paired microvalve 126 are both in a closed state to keep the single second target object B in the paired flow channel 136. It should be noted that, in this embodiment, the second microvalve 122 being in a closed state specifically refers to switching from an open state to a closed state, and the paired microvalve 126 being in a closed state specifically refers to remaining in a closed state.

[0086] In some specific embodiments, the detection module is specifically a visual detection module, which includes a camera and a controller, and the controller is configured to control the camera to capture an image. After the camera captures the image, the controller is further configured to identify a single first target object A and a single second target object B based on the image.

[0087] In some other specific embodiments, the detection module is specifically a fluorescence detection module, which includes a first light source, a second light source, a first light detection device, a second light detection device and a controller, referring to Figure 3 , the controller is configured to control the first light source to emit the first detection light D to the first flow channel 131, the first detection light D can excite the first fluorescence after irradiating the single first target A, and the first light detection device can receive the first fluorescence excited by the single first target A. For example, the first light source is a laser, and the first light detection device is a photomultiplier tube. After receiving the first fluorescence emitted by the single first target A, the photomultiplier tube can convert the optical signal into an electrical signal and transmit it to the controller. The controller is also configured to control the second light source to emit the second detection light E to the second flow channel 132, the second detection light E can excite the second fluorescence after irradiating the single second target B, and when the second light detection device detects the second fluorescence, the controller recognizes the single second target B.

[0088] In other specific embodiments, the detection module is specifically an electrode detection module, which includes a first detection electrode, a second detection electrode and a controller, the first detection electrode extends into the first flow channel 131, and the second detection electrode extends into the second flow channel 132. When a single first target A passes through the first detection electrode, the first detection electrode generates a corresponding signal, and the controller is configured to identify the single first target A based on the signal detected by the first detection electrode. Specifically, the first detection electrode includes a positive electrode and a negative electrode, and the positive electrode and the negative electrode are arranged in parallel. When the microfluidic system includes a microfluidic chip 100, the first detection electrode can be a metal layer arranged between the control layer 120 and the flow channel layer 130 of the microfluidic chip 100. The second detection electrode can be understood with reference to the first detection electrode.

[0089] The second embodiment of the present invention discloses a microfluidic system for target pairing, referring to Figures 1 to 3 , including a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134 and a matching flow channel 136, wherein the first flow channel 131 is used for passing a first liquid containing a first target, the second flow channel 132 is used for passing a second liquid containing a second target, the buffer flow channel 134 is used for passing a buffer, the oil flow channel 133 is used for passing an oil that is not soluble in the first liquid, the second liquid and the buffer, and the matching flow channel 136 is used for allowing a single first target A and a single second target B to stay. The matching flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132 and the buffer flow channel 134 are all connected to the matching flow channel 136. In this embodiment, the first target is a cell and the second target is a microsphere for description. It can be understood by those skilled in the art that the first target can be a cell and the second target can also be a cell.

[0090] The microfluidic system of the present embodiment further includes a plurality of microvalves, specifically including a paired microvalve 126 arranged corresponding to the paired flow channel 136, a first microvalve 121 arranged corresponding to the first flow channel 131, a second microvalve 122 arranged corresponding to the second flow channel 132, and a buffer solution microvalve 124 arranged corresponding to the buffer solution flow channel 134, wherein the paired microvalve 126 is used to control the on-off of the paired flow channel 136, the first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer solution microvalve 124 is used to control the on-off of the second flow channel 132. 124 is used to control the on-off of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the on-off of the first flow channel 131 of the first microvalve 121 controller means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a 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] For ease of understanding, please refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are explained, such as Figure 4 As shown, the microfluidic system includes a microfluidic chip 100, and the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 which are stacked in sequence. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS). Among them, the flow channel layer 130 has the aforementioned first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste liquid flow channel 135 and the matching flow channel 136. The control layer 120 has the aforementioned first microvalve 121, the second microvalve 122, the buffer microvalve 124, the waste liquid microvalve 125 and the matching microvalve 126, as well as microvalve control flow channels corresponding to each microvalve. Refer to Figure 5 Taking the first microvalve 121 as an example, the first microvalve 121 includes a diaphragm 1211 disposed between the first flow channel 131 (specifically, the first microvalve section 1311 described below) and the first microvalve control flow channel 139. When the first microvalve 121 is in a state as Figure 5 In the open state shown in a in FIG. 1 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first microvalve section 1311; when the diaphragm 1211 is driven by the liquid or gas in the first microvalve control channel 139 and protrudes toward the first channel 131 to be in a state as shown in FIG. Figure 5 In the closed state shown in b in FIG. 1 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first microvalve section 1311, and the first liquid cannot pass through the first microvalve section 1311. Figure 5In the embodiment shown, the upper inner wall surface of the first microvalve segment 1311 is set as an arc surface protruding away from the first microvalve 121, specifically a semicircular arc surface, which is convenient for fitting with the diaphragm 1211 protruding toward the first microvalve segment 1311, thereby ensuring the cutoff effect. The second microvalve segment 1321 of the second flow channel 132 can be understood with reference to the first microvalve segment 1311.

[0092] In this embodiment, refer to Figure 3 From step c to step d, 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 a closed state (the microvalve is filled in black to indicate that it is in a closed state), and the paired microvalve 126 and the buffer microvalve 124 are in an open state (the microvalve is filled in gray to indicate that it is in an open state), at this time, the buffer in the buffer flow channel 134 can deliver 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. In this way, through the single paired The flow channel 136 is used to temporarily store a single first target object A and a single second target object B, and is provided with a separate buffer flow channel 134. The single first target object A and the single second target object B are pushed into the oil by the buffer, and there is no need to push the single first target object A and the single second target object B by the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0093] On this basis, the maximum height of the oil flow channel 133 in this embodiment is 80 microns to 200 microns. In the actual packaging process, the encapsulated droplets may have a large-area contact with the flow channel wall of the oil flow channel 133, causing the droplets to adhere to the flow channel wall and be broken as the oil flows. By setting the maximum height of the oil flow channel 133, this embodiment can reduce the probability of the droplets contacting the flow channel wall of the oil flow channel 133, thereby reducing the risk of droplet breakage. Exemplarily, the maximum height of the oil flow channel 133 is 80 microns, 90 microns, 100 microns, 110 microns, 120 microns, 130 microns, 140 microns, 150 microns, 160 microns, 170 microns, 180 microns, 190 microns and 200 microns.

[0094] On the basis of the second embodiment, in some embodiments of the present invention, the upper inner wall surface and the lower inner wall surface of the oil flow channel 133 are parallel planes to each other, which can further reduce the probability of the droplet contacting the flow channel wall of the oil flow channel 133. In some specific embodiments, the cross section of the oil flow channel 133 is set to be rectangular, which is convenient for the preparation of the flow channel.

[0095] The third embodiment of the present invention discloses a microfluidic system for target pairing, referring to Figures 1 to 3 , including a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134 and a matching flow channel 136, wherein the first flow channel 131 is used for passing a first liquid containing a first target, the second flow channel 132 is used for passing a second liquid containing a second target, the buffer flow channel 134 is used for passing a buffer, the oil flow channel 133 is used for passing an oil that is not soluble in the first liquid, the second liquid and the buffer, and the matching flow channel 136 is used for allowing a single first target A and a single second target B to stay. The matching flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132 and the buffer flow channel 134 are all connected to the matching flow channel 136. In this embodiment, the first target is a cell and the second target is a microsphere for description. It can be understood by those skilled in the art that the first target can be a cell and the second target can also be a cell.

[0096] The microfluidic system of the present embodiment further includes a plurality of microvalves, specifically including a paired microvalve 126 arranged corresponding to the paired flow channel 136, a first microvalve 121 arranged corresponding to the first flow channel 131, a second microvalve 122 arranged corresponding to the second flow channel 132, and a buffer solution microvalve 124 arranged corresponding to the buffer solution flow channel 134, wherein the paired microvalve 126 is used to control the on-off of the paired flow channel 136, the first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer solution microvalve 124 is used to control the on-off of the second flow channel 132. 124 is used to control the on-off of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the on-off of the first flow channel 131 of the first microvalve 121 controller means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a 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.

[0097] For ease of understanding, please refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are explained, such as Figure 4As shown, the microfluidic system includes a microfluidic chip 100, and the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 which are stacked in sequence. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS). Among them, the flow channel layer 130 has the aforementioned first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste liquid flow channel 135 and the matching flow channel 136. The control layer 120 has the aforementioned first microvalve 121, the second microvalve 122, the buffer microvalve 124, the waste liquid microvalve 125 and the matching microvalve 126, as well as microvalve control flow channels corresponding to each microvalve. Refer to Figure 5 Taking the first microvalve 121 as an example, the first microvalve 121 includes a diaphragm 1211 disposed between the first flow channel 131 (specifically, the first microvalve section 1311 described below) and the first microvalve control flow channel 139. When the first microvalve 121 is in a state as Figure 5 In the open state shown in a in FIG. 1 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first microvalve section 1311; when the diaphragm 1211 is driven by the liquid or gas in the first microvalve control channel 139 and protrudes toward the first channel 131 to be in a state as shown in FIG. Figure 5 In the closed state shown in b in FIG. 1 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first microvalve section 1311, and the first liquid cannot pass through the first microvalve section 1311. Figure 5 In the embodiment shown, the upper inner wall surface of the first microvalve segment 1311 is set as an arc surface protruding away from the first microvalve 121, specifically a semicircular arc surface, which is convenient for fitting with the diaphragm 1211 protruding toward the first microvalve segment 1311, thereby ensuring the cutoff effect. The second microvalve segment 1321 of the second flow channel 132 can be understood with reference to the first microvalve segment 1311.

[0098] In this embodiment, refer to Figure 3From step c to step d, 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 a closed state (the microvalve is filled in black to indicate that it is in a closed state), and the paired microvalve 126 and the buffer microvalve 124 are in an open state (the microvalve is filled in gray to indicate that it is in an open state), at this time, the buffer in the buffer flow channel 134 can deliver 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. In this way, through the single paired The flow channel 136 is used to temporarily store a single first target object A and a single second target object B, and is provided with a separate buffer flow channel 134. The single first target object A and the single second target object B are pushed into the oil by the buffer, and there is no need to push the single first target object A and the single second target object B by the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0099] On this basis, the microfluidic system in this embodiment further includes a first sheath liquid flow channel 137, which is connected to the first flow channel 131 and is used to input a first sheath flow that wraps the first liquid into the first flow channel 131. In this embodiment, by setting the sheath liquid to constrain the first liquid, the first liquid can flow in the central area of ​​the flow channel, thereby preventing the first target in the first liquid from being too close to the inner wall surface of the flow channel, resulting in a large flow rate difference between different first targets.

[0100] In some specific embodiments, referring to Figure 1 The first sheath liquid flow channel 137 includes two first branch flow channels 1371 , and the two first branch flow channels 1371 are connected to the first flow channel 131 from both sides of the first flow channel 131 , so that the first liquid can be confined between the two sheath flows.

[0101] In other embodiments, reference Figure 1 The microfluidic system further includes a second sheath liquid flow channel 138, which is connected to the second flow channel 132 and is used to input a second sheath flow enveloping the second liquid into the second flow channel 132. In this embodiment, by setting the sheath liquid to constrain the second liquid, the second liquid can flow in the central area of ​​the flow channel, resulting in a large flow rate difference between different second targets.

[0102] In some specific embodiments, referring to Figure 1The second sheath liquid flow channel 138 includes two second branch flow channels 1381 , and the two second branch flow channels 1381 are respectively connected to the second flow channel 132 from both sides of the second flow channel 132 , so that the second liquid can be confined between the two sheath flows.

[0103] The fourth embodiment of the present invention discloses a microfluidic system for target pairing, referring to Figures 1 to 3 , including a first flow channel 131, a second flow channel 132, an oil flow channel 133, a buffer flow channel 134 and a matching flow channel 136, wherein the first flow channel 131 is used for passing a first liquid containing a first target, the second flow channel 132 is used for passing a second liquid containing a second target, the buffer flow channel 134 is used for passing a buffer, the oil flow channel 133 is used for passing an oil that is not soluble in the first liquid, the second liquid and the buffer, and the matching flow channel 136 is used for allowing a single first target A and a single second target B to stay. The matching flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132 and the buffer flow channel 134 are all connected to the matching flow channel 136. In this embodiment, the first target is a cell and the second target is a microsphere for description. It can be understood by those skilled in the art that the first target can be a cell and the second target can also be a cell.

[0104] The microfluidic system of the present embodiment further includes a plurality of microvalves, specifically including a paired microvalve 126 arranged corresponding to the paired flow channel 136, a first microvalve 121 arranged corresponding to the first flow channel 131, a second microvalve 122 arranged corresponding to the second flow channel 132, and a buffer solution microvalve 124 arranged corresponding to the buffer solution flow channel 134, wherein the paired microvalve 126 is used to control the on-off of the paired flow channel 136, the first microvalve 121 is used to control the on-off of the first flow channel 131, the second microvalve 122 is used to control the on-off of the second flow channel 132, and the buffer solution microvalve 124 is used to control the on-off of the second flow channel 132. 124 is used to control the on-off of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the on-off of the first flow channel 131 of the first microvalve 121 controller means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a 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.

[0105] For ease of understanding, please refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are explained, such as Figure 4As shown, the microfluidic system includes a microfluidic chip 100, and the microfluidic chip 100 includes a base layer 110, a control layer 120 and a flow channel layer 130 which are stacked in sequence. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS). Among them, the flow channel layer 130 has the aforementioned first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste liquid flow channel 135 and the matching flow channel 136. The control layer 120 has the aforementioned first microvalve 121, the second microvalve 122, the buffer microvalve 124, the waste liquid microvalve 125 and the matching microvalve 126, as well as microvalve control flow channels corresponding to each microvalve. Refer to Figure 5 Taking the first microvalve 121 as an example, the first microvalve 121 includes a diaphragm 1211 disposed between the first flow channel 131 (specifically, the first microvalve section 1311 described below) and the first microvalve control flow channel 139. When the first microvalve 121 is in a state as Figure 5 In the open state shown in a in FIG. 1 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first microvalve section 1311; when the diaphragm 1211 is driven by the liquid or gas in the first microvalve control channel 139 and protrudes toward the first channel 131 to be in a state as shown in FIG. Figure 5 In the closed state shown in b in FIG. 1 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first microvalve section 1311, and the first liquid cannot pass through the first microvalve section 1311. Figure 5 In the embodiment shown, the upper inner wall surface of the first microvalve segment 1311 is set as an arc surface protruding away from the first microvalve 121, specifically a semicircular arc surface, which is convenient for fitting with the diaphragm 1211 protruding toward the first microvalve segment 1311, thereby ensuring the cutoff effect. The second microvalve segment 1321 of the second flow channel 132 can be understood with reference to the first microvalve segment 1311.

[0106] In this embodiment, refer to Figure 3From step c to step d, 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 a closed state (the microvalve is filled in black to indicate that it is in a closed state), and the paired microvalve 126 and the buffer microvalve 124 are in an open state (the microvalve is filled in gray to indicate that it is in an open state), at this time, the buffer in the buffer flow channel 134 can deliver 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. In this way, through the single paired The flow channel 136 is used to temporarily store a single first target object A and a single second target object B, and is provided with a separate buffer flow channel 134. The single first target object A and the single second target object B are pushed into the oil by the buffer, and there is no need to push the single first target object A and the single second target object B by the first liquid and the second liquid. Therefore, the first flow channel 131 and the second flow channel 132 can be kept in a cut-off state during the encapsulation process, thereby completely preventing other first targets and / or other second targets from entering the droplet C, which is beneficial to improving the success rate of encapsulation and reducing cell loss caused by multiple encapsulation.

[0107] In addition, the microfluidic system further includes a waste liquid flow channel 135, which is used to discharge the first liquid and the second liquid, and the waste liquid flow channel 135 is connected to the matching flow channel 136. In addition, the microfluidic system further includes a waste liquid microvalve 125 arranged corresponding to the waste liquid flow channel 135, and the waste liquid microvalve 125 is used to control the on-off of the waste liquid flow channel 135. When the matching microvalve 126 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, the first liquid in the first flow channel 131 can flow out through the matching flow channel 136 and the waste liquid flow channel 135. In other embodiments, when the matching microvalve 126 is in a closed state and the second microvalve 122 and the waste liquid microvalve 125 are in an open state, the liquid in the second flow channel 132 can flow out through the matching flow channel 136 and the waste liquid flow channel 135. It should be noted that the first target object and the second target object will follow the flow of the first liquid and the second liquid respectively and gradually approach and reach the matching channel 136. When the first target object and the second target object have not yet reached the matching channel 136, the first channel 131 and the second channel 132 will continue to discharge the first liquid and the second liquid, and these first liquids and the second liquids need to be discharged as waste liquids.

[0108] On this basis, refer to Figure 1 , Figure 2 , along the flow direction of the buffer solution in the paired flow channel 136, for example Figure 1 , Figure 2From top to bottom, the waste liquid flow channel 135 in this embodiment is located between the first flow channel 131 and the second flow channel 132. The microfluidic system further includes a first stop microvalve 127, which is used to control the on-off of the paired flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131. Figure 1 , Figure 2 From top to bottom, the first stop microvalve 127 is disposed on the paired flow channel 136 between the waste liquid flow channel 135 and the first flow channel 131. By disposing the first stop microvalve 127, this embodiment can prevent the first target object that has entered the paired flow channel 136 from being driven out of the paired flow channel 136 by the second liquid, resulting in only the second target object in the encapsulated droplet, thereby ensuring the encapsulation success rate. It should be noted that when the first target object is a target object such as a tumor cell, the number of the first target object in the sample is small and the cost is also high. By disposing the first stop microvalve 127, this embodiment can also reduce the waste of the first target object.

[0109] Based on the fourth embodiment, in some embodiments of the present invention, combined with Figure 1 , Figure 2 It is understood that the microfluidic system is configured as follows: when a single first target object A is located in the matching flow channel 136, the first stop microvalve 127 is switched from an open state to a closed state. At this time, the matching flow channel 136 where the single first target object A is located and the matching flow channel 136 through which the second liquid flows are isolated by the first stop microvalve 127, and the flow of the second liquid will not drive the first target object.

[0110] The microfluidic system is also configured as follows: when there is a single first target A and a single second target B in the pairing flow channel 136, the first microvalve 121, the second microvalve 122 and the waste liquid microvalve 125 are in a closed state, and the pairing microvalve 126, the buffer microvalve 124 and the first stop microvalve 127 are in an open state, so that the buffer in the buffer flow channel 134 can deliver the single first target A and the single second target B in the pairing flow channel 136 into the oil in the oil flow channel 133 to form droplets C.

[0111] In this embodiment, by controlling the on-off of the first stop microvalve 127 , the first target object can be stored in the pairing flow channel 136 during the waiting process for pairing without affecting the pairing and packaging of the first target object and the second target object.

[0112] It should be noted that, before the first stop microvalve 127 is in the closed state, the second microvalve 122 can be in the open state all the time, so that the second liquid is continuously discharged from the waste liquid channel 135 (that is, the second target object B is not captured). The second microvalve 122 can also be in the closed state first, and when the first stop microvalve 127 is in the closed state, the second microvalve 122 is opened again to capture the subsequent single second target object B.

[0113] On the basis of the fourth embodiment, in some embodiments of the present invention, when there is no single first target object A in the matching flow channel 136, the matching microvalve 126 is in a closed state and the first microvalve 121, the first stop microvalve 127 and the waste liquid microvalve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the matching flow channel 136 and the waste liquid flow channel 135, thereby allowing the first target object to flow to the matching flow channel 136.

[0114] In other embodiments, when there is no single second target object B in the matching flow channel 136, the matching microvalve 126 is in a closed state and the second microvalve 122 and the waste liquid microvalve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the matching flow channel 136 and the waste liquid flow channel 135, thereby allowing the second target object to flow into the matching flow channel 136.

[0115] The fifth embodiment of the present invention discloses a microfluidic system for target pairing, which differs from the fourth embodiment in that: the fourth embodiment is provided with a first stop microvalve 127, which is used to control the on-off of the pairing flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131, and the present embodiment is provided with a second stop microvalve 128, which is used to control the on-off of the pairing flow channel 136 located between the waste liquid flow channel 135 and the second flow channel 132. Exemplarily, along Figure 7 From top to bottom, the second stop microvalve 128 is disposed on the matching flow channel 136 between the waste liquid flow channel 135 and the second flow channel 132. By disposing the second stop microvalve 128, the second target object that has entered the matching flow channel 136 can be prevented from being driven out of the matching flow channel 136 by the first liquid, resulting in only the first target object in the encapsulated droplet, thereby ensuring the encapsulation success rate.

[0116] In some specific embodiments, in combination Figure 7 It is understood that the microfluidic system is configured as follows: when a single second target object B is located in the matching flow channel 136, the second stop microvalve 128 is switched from an open state to a closed state. At this time, the matching flow channel 136 where the single second target object B is located and the matching flow channel 136 through which the first liquid flows are isolated by the second stop microvalve 128, and the flow of the first liquid will not drive the second target object.

[0117] The microfluidic system is also configured as follows: when there is a single first target A and a single second target B in the pairing flow channel 136, the first microvalve 121, the second microvalve 122 and the waste liquid microvalve 125 are in a closed state, and the pairing microvalve 126, the buffer microvalve 124 and the second shut-off microvalve 128 are in an open state, so that the buffer in the buffer flow channel 134 can deliver the single first target A and the single second target B in the pairing flow channel 136 into the oil in the oil flow channel 133 to form droplets C.

[0118] In this embodiment, by controlling the on-off of the second stop microvalve 128 , the second object can be stored in the pairing flow channel 136 during the waiting process for pairing without affecting the pairing and packaging of the first object and the second object.

[0119] On the basis of the fifth embodiment, in some embodiments of the present invention, when there is no single first target object A in the matching flow channel 136, the matching microvalve 126 is in a closed state and the first microvalve 121 and the waste liquid microvalve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the matching flow channel 136 and the waste liquid flow channel 135, thereby allowing the first target object to flow to the matching flow channel 136.

[0120] In other embodiments, when there is no single second target object B in the matching flow channel 136, the matching microvalve 126 is in a closed state and the second microvalve 122, the second stop microvalve 128 and the waste liquid microvalve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the matching flow channel 136 and the waste liquid flow channel 135, thereby allowing the second target object to flow into the matching flow channel 136.

[0121] The sixth embodiment of the present invention discloses a microfluidic system for target object pairing, which differs from the fourth embodiment in that the waste liquid channel 135 in the fourth embodiment is located between the first channel 131 and the second channel 132, and is provided with a first stop microvalve 127. The first stop microvalve 127 is used to control the on-off of the pairing channel 136 located between the waste liquid channel 135 and the first channel 131. In this embodiment, no stop microvalve is provided, but the maintenance of a single first target position A is achieved through the positional relationship of the channels.

[0122] Specifically, refer to Figure 8 , along the flow direction of the buffer solution in the paired flow channel 136, for example Figure 8From top to bottom, the waste liquid channel 135, the second channel 132 and the first channel 131 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single first target A is located in the matching channel 136, the second microvalve 122 is in a closed state again so that the single second target B is located in the matching channel 136, that is, this embodiment needs to first ensure that the single first target A is located in the matching channel 136 (at this time, the first microvalve 121 is already in a closed state), and then the single second target B is located in the matching channel 136. Exemplarily, the second microvalve 122 is in a closed state before the single first target A is located in the matching channel 136, and the second microvalve 122 is opened again after the single first target A is located in the matching channel 136. When the detection module detects the single second target B, the second microvalve 122 is closed again, so that the single second target B can stop in the matching channel 136.

[0123] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the second channel 132, the second liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off first channel 131, thereby preventing a single first target object A from being carried away by the second liquid.

[0124] The seventh embodiment of the present invention discloses a microfluidic system for target object pairing, which differs from the fourth embodiment in that the waste liquid channel 135 in the fourth embodiment is located between the first channel 131 and the second channel 132, and is provided with a first stop microvalve 127. The first stop microvalve 127 is used to control the on-off of the pairing channel 136 located between the waste liquid channel 135 and the first channel 131. In this embodiment, no stop microvalve is provided, but the maintenance of a single first target position A is achieved by the positional relationship of the channels.

[0125] Specifically, refer to Fig. 9 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig. 9 From top to bottom, the waste liquid channel 135, the first channel 131 and the second channel 132 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single second target B is located in the matching channel 136, the first microvalve 121 is in a closed state again so that the single first target A is located in the matching channel 136, that is, this embodiment needs to first ensure that the single second target N is located in the matching channel 136 (at this time, the second microvalve 122 is already in a closed state), and then the single first target A is located in the matching channel 136. Exemplarily, the first microvalve 121 is in a closed state before the single second target B is located in the matching channel 136, and the first microvalve 121 is opened again after the single second target B is located in the matching channel 136. When the detection module detects the single first target A, the first microvalve 121 is closed again, so that the single first target A can stop in the matching channel 136.

[0126] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the first channel 131, the first liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off second channel 132, thereby preventing a single second target object B from being carried away by the first liquid.

[0127] The eighth embodiment of the present invention discloses a microfluidic system for target object pairing, which differs from the fourth embodiment in that the waste liquid channel 135 in the fourth embodiment is located between the first channel 131 and the second channel 132, and is provided with a first stop microvalve 127. The first stop microvalve 127 is used to control the on-off of the pairing channel 136 located between the waste liquid channel 135 and the first channel 131. In this embodiment, no stop microvalve is provided, but the maintenance of a single first target position A is achieved by the positional relationship of the channels.

[0128] Specifically, refer to Fig.10 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig.10 From top to bottom, the second flow channel 132, the first flow channel 131 and the waste liquid flow channel 135 are arranged in sequence. On this basis, the microfluidic system is configured as follows: when the single second target object B is located in the matching flow channel 136, the first microvalve 121 is in a closed state again so that the single first target object A is located in the matching flow channel 136, that is, this embodiment needs to first ensure that the single second target object N is located in the matching flow channel 136 (at this time, the second microvalve 122 is already in a closed state), and then the single first target object A is located in the matching flow channel 136. Exemplarily, the first microvalve 121 is in a closed state before the single second target object B is located in the matching flow channel 136, and the first microvalve 121 is opened again after the single second target object B is located in the matching flow channel 136. When the detection module detects the single first target object A, the first microvalve 121 is closed again, so that the single first target object A can stop in the matching flow channel 136.

[0129] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the first channel 131, the first liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off second channel 132, thereby preventing a single second target object B from being carried away by the first liquid.

[0130] The ninth embodiment of the present invention discloses a microfluidic system for target object pairing, which differs from the fourth embodiment in that the waste liquid channel 135 in the fourth embodiment is located between the first channel 131 and the second channel 132, and is provided with a first stop microvalve 127. The first stop microvalve 127 is used to control the on-off of the pairing channel 136 located between the waste liquid channel 135 and the first channel 131. In this embodiment, no stop microvalve is provided, but the maintenance of a single first target position A is achieved by the positional relationship of the channels.

[0131] Specifically, refer to Fig.11 , along the flow direction of the buffer solution in the paired flow channel 136, for example Fig.11 From top to bottom, the first flow channel 131, the second flow channel 132 and the waste liquid flow channel 135 are arranged in sequence. On this basis, the microfluidic system is configured as follows: after the single first target A is located in the matching flow channel 136, the second microvalve 122 is in a closed state again so that the single second target B is located in the matching flow channel 136, that is, this embodiment needs to first ensure that the single first target A is located in the matching flow channel 136 (at this time, the first microvalve 121 is already in a closed state), and then the single second target B is located in the matching flow channel 136. Exemplarily, the second microvalve 122 is in a closed state before the single first target A is located in the matching flow channel 136, and the second microvalve 122 is opened again after the single first target A is located in the matching flow channel 136. When the detection module detects the single second target B, the second microvalve 122 is closed again, so that the single second target B can stop in the matching flow channel 136.

[0132] In this embodiment, since the waste liquid channel 135 is arranged on a side close to the second channel 132, the second liquid will flow toward the waste liquid channel 135 instead of flowing toward the cut-off first channel 131, thereby preventing a single first target object A from being carried away by the second liquid.

[0133] The embodiments of the present invention are described in detail above in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge of ordinary technicians in the relevant technical field without departing from the purpose of the present invention. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a matching flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the matching flow channel, the first flow channel is used for a first liquid containing a first target to pass through, and the second flow channel is used for a second liquid containing a second target to pass through; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; The first flow channel includes a first microvalve section corresponding to the first microvalve and a first flow section different from the first microvalve section, and the upper inner wall surface and the lower inner wall surface of the first flow section are parallel planes to each other; And / or, the second flow channel includes a second microvalve section corresponding to the second microvalve, and a second flow section different from the second microvalve section, and the upper inner wall surface and the lower inner wall surface of the second flow section are planes parallel to each other.

2. The microfluidic system for target pairing according to claim 1, characterized in that: The cross section of the first flow section is set to be a rectangle, and / or the cross section of the second flow section is set to be a rectangle.

3. The microfluidic system for target pairing according to claim 2, characterized in that: The width of the first flow segment is 50 micrometers to 150 micrometers, and / or the width of the second flow segment is 50 micrometers to 150 micrometers.

4. The microfluidic system for target pairing according to claim 1, characterized in that: The upper inner wall surface of the first microvalve section is configured as a curved surface convexly facing away from the first microvalve, and / or the upper inner wall surface of the second microvalve section is configured as a curved surface convexly facing away from the second microvalve.

5. The microfluidic system for target pairing according to claim 4, characterized in that: The cross section of the first microvalve section is set to be semicircular, and / or the cross section of the second microvalve section is set to be semicircular.

6. The microfluidic system for target pairing according to claim 1, characterized in that: The maximum height of the oil flow channel is 80 microns to 200 microns.

7. The microfluidic system for target pairing according to claim 1, characterized in that: The microfluidic system further comprises a first sheath liquid flow channel, the first sheath liquid flow channel being in communication with the first flow channel and being used for inputting a first sheath flow encapsulating the first liquid into the first flow channel; And / or, the microfluidic system further comprises a second sheath liquid flow channel, wherein the second sheath liquid flow channel is connected to the second flow channel and is used for inputting a second sheath flow enveloping the second liquid into the second flow channel.

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

9. The microfluidic system for target pairing according to claim 8, characterized in that: Along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a first stop microvalve, which is used to control the opening and closing of the paired flow channel located between the waste liquid flow channel and the first flow channel.

10. The microfluidic system for target pairing according to claim 9, characterized in that: The microfluidic system is configured as follows: when the single first target is located in the pairing flow channel, the first shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the first shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

11. The microfluidic system for target pairing according to claim 8, characterized in that: Along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a second stop microvalve, which is used to control the opening and closing of the paired flow channel located between the waste liquid flow channel and the second flow channel.

12. The microfluidic system for target pairing according to claim 11, characterized in that: The microfluidic system is configured as follows: when the single second target is located in the paired flow channel, the second shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve, the buffer microvalve and the second shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets.

13. The microfluidic system for target pairing according to claim 8, characterized in that: Along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are arranged in sequence, and the microfluidic system is configured such that: when the single first target object is located in the paired flow channel, the second microvalve is in a closed state again so that the single second target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the first flow channel and the second flow channel are sequentially arranged, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is again in a closed state so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the second flow channel, the first flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is in a closed state again so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured as follows: when the single first target object is located in the paired flow channel, the second microvalve is closed again to allow the single second target object to be located in the paired flow channel.

14. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a matching flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the matching flow channel, the first flow channel is used for a first liquid containing a first target to pass through, and the second flow channel is used for a second liquid containing a second target to pass through; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, the maximum height of the oil flow channel is 80 microns to 200 microns.

15. The microfluidic system for target pairing according to claim 14, characterized in that: The upper inner wall surface and the lower inner wall surface of the oil flow channel are planes parallel to each other.

16. The microfluidic system for target pairing according to claim 15, characterized in that: The cross section of the oil flow channel is set to be rectangular.

17. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel and a matching flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all connected to the matching flow channel, the first flow channel is used for a first liquid containing a first target to pass through, and the second flow channel is used for a second liquid containing a second target to pass through; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, and a buffer microvalve arranged corresponding to the buffer flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer microvalve is used to control the on-off of the buffer flow channel; The microfluidic system is configured such that: when a single first target and a single second target exist in the paired flow channel, the first microvalve and the second microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, the microfluidic system further comprises a first sheath liquid flow channel, the first sheath liquid flow channel being in communication with the first flow channel and being used for inputting a first sheath flow enveloping the first liquid into the first flow channel; And / or, the microfluidic system further comprises a second sheath liquid flow channel, wherein the second sheath liquid flow channel is connected to the second flow channel and is used for inputting a second sheath flow enveloping the second liquid into the second flow channel.

18. The microfluidic system for target pairing according to claim 17, characterized in that: The first sheath fluid flow channel comprises two first branch flow channels, and the two first branch flow channels are respectively connected to the first flow channel from both sides of the first flow channel; And / or, the second sheath fluid flow channel includes two second branch flow channels, and the two second branch flow channels are respectively connected to the second flow channel from both sides of the second flow channel.

19. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a matching flow channel and a waste flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all connected to the matching flow channel, the first flow channel is used for passing a first liquid containing a first target object, and the second flow channel is used for passing a second liquid containing a second target object; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, a buffer solution microvalve arranged corresponding to the buffer solution flow channel, and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, the buffer solution microvalve is used to control the on-off of the buffer solution flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Among them, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a first stop microvalve, which is used to control the opening and closing of the paired flow channel located between the waste liquid flow channel and the first flow channel.

20. The microfluidic system for target pairing according to claim 19, characterized in that: The microfluidic system is configured as follows: when the single first target is located in the pairing flow channel, the first shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the pairing flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the pairing microvalve, the buffer microvalve and the first shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport 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.

21. The microfluidic system for target pairing according to claim 20, characterized in that: When the single first target does not exist in the paired flow channel, the paired microvalve is in a closed state and the first microvalve, the first stop microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the single second target object does not exist in the paired flow channel, the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

22. A microfluidic system for target pairing, characterized in that: The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a matching flow channel and a waste flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all connected to the matching flow channel, the first flow channel is used for passing a first liquid containing a first target object, and the second flow channel is used for passing a second liquid containing a second target object; The microfluidic system further comprises a paired microvalve arranged corresponding to the paired flow channel, a first microvalve arranged corresponding to the first flow channel, a second microvalve arranged corresponding to the second flow channel, a buffer solution microvalve arranged corresponding to the buffer solution flow channel, and a waste liquid microvalve arranged corresponding to the waste liquid flow channel, wherein the paired microvalve is used to control the on-off of the paired flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, the buffer solution microvalve is used to control the on-off of the buffer solution flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Among them, along the flow direction of the buffer solution in the paired flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system also includes a second stop microvalve, which is used to control the on-off of the paired flow channel located between the waste liquid flow channel and the second flow channel.

23. The microfluidic system for target pairing according to claim 22, characterized in that: The microfluidic system is configured as follows: when the single second target is located in the paired flow channel, the second shut-off microvalve is switched from an open state to a closed state, and when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve, the buffer microvalve and the second shut-off microvalve are in an open state, so that the buffer in the buffer flow channel can transport the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets.

24. The microfluidic system for target pairing according to claim 23, characterized in that: When the single first target does not exist in the paired flow channel, the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, so that the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; And / or, when the single second target object does not exist in the paired flow channel, the paired microvalve is in a closed state and the second microvalve, the second stop microvalve and the waste liquid microvalve are in an open state, so that the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel.

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 flow channel, a matching flow channel and a waste liquid flow channel, the matching flow channel is connected to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste liquid flow channel are all connected to the matching flow channel, and the waste liquid flow channel is located between the first flow channel and the second flow channel, the first flow channel is used for a first liquid containing a first target object to pass through, and the second flow channel is used for a second liquid containing a second target object to pass through; the microfluidic system also includes a matching microvalve corresponding to the matching flow channel, a first microvalve corresponding to the first flow channel, a second microvalve corresponding to the second flow channel, a buffer microvalve corresponding to the buffer flow channel and a waste liquid microvalve corresponding to the waste liquid flow channel, the matching microvalve is used to control the on-off of the matching 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, the buffer microvalve is used to control the on-off of the buffer flow channel, and the waste liquid microvalve is used to control the on-off of the waste liquid flow channel; The microfluidic system is configured as follows: when the paired microvalve is in a closed state and the first microvalve and the waste liquid microvalve are in an open state, the liquid in the first flow channel can flow out through the paired flow channel and the waste liquid flow channel; when the paired microvalve is in a closed state and the second microvalve and the waste liquid microvalve are in an open state, the liquid in the second flow channel can flow out through the paired flow channel and the waste liquid flow channel; when a single first target and a single second target exist in the paired flow channel, the first microvalve, the second microvalve and the waste liquid microvalve are in a closed state, and the paired microvalve and the buffer microvalve are in an open state, so that the buffer in the buffer flow channel delivers the single first target and the single second target in the paired flow channel into the oil in the oil flow channel to form droplets; Wherein, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are arranged in sequence, and the microfluidic system is configured such that: when the single first target object is located in the paired flow channel, the second microvalve is in a closed state again so that the single second target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer in the paired flow channel, the waste liquid flow channel, the first flow channel and the second flow channel are sequentially arranged, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is again in a closed state so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the second flow channel, the first flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured such that: when the single second target object is located in the paired flow channel, the first microvalve is in a closed state again so that the single first target object is located in the paired flow channel; Alternatively, along the flow direction of the buffer solution in the paired flow channel, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence, and the microfluidic system is configured as follows: when the single first target object is located in the paired flow channel, the second microvalve is closed again to allow the single second target object to be located in the paired flow channel.

Images