Microfluidic system for target object pairing
By designing a microfluidic system with parallel inner wall flow channels and microvalve control, the problems of uneven flow rate and droplet breakage in single-cell sequencing were solved, achieving efficient encapsulation and stable pairing of target materials.
Patent Information
- Application Number
- CN202520020465.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-06
- Publication Date
- 2026-01-16
- Estimated Expiration
- 2035-01-06
AI Technical Summary
In existing single-cell sequencing technologies, the cross-sectional shape of the cell flow channel and microsphere flow channel leads to uneven cell flow rate, increases the interception range, affects capture efficiency, and makes droplets easily flushed out or broken, reducing the success rate of target encapsulation.
Design a microfluidic system including a flow channel structure with parallel inner walls and microvalve control to ensure that the target material is stably paired in the flow channel and enters the oil flow channel to form droplets. By setting up sheath fluid flow channels and waste fluid flow channels, the flow velocity difference and droplet breakage risk are reduced.
It improves the success rate of target capture, reduces the risk of droplet breakage, and ensures the stability and accuracy of encapsulation.
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Figure CN223800541U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The utility model relates to single cell sequencing technical field especially a kind of microfluidic system for target pairing. BACKGROUND
[0002] Single-cell RNA sequencing technology (scRNA-seq) reveals the heterogeneity of cells within tissues. Compared with traditional gene sequencing technology, single-cell sequencing technology has the advantages of high precision and high resolution, can provide single-cell level information, reveal the heterogeneity and complexity of expression within tissues, and has wide application in the fields of cancer, reproduction, immunity and development. Compared with traditional sequencing, single-cell sequencing needs to separate cell population in tissue or body fluid into single cells. There is a cell pairing system at present, which is provided with cell flow channel, microsphere flow channel, pairing flow channel, buffer flow channel, oil flow channel, detection module and corresponding control microvalve, the first liquid containing cells flows in the cell flow channel, the second liquid containing microspheres flows in the microsphere flow channel, after the detection module detects cells or microspheres, a certain time interval is controlled to close the flow channel by corresponding microvalve, so that single cell and single microsphere can be stopped in the pairing flow channel, and then the buffer in the separate buffer flow channel is used to push single cell and single microsphere into the oil in the oil flow channel to encapsulate into droplet.
[0003] However, this cell pairing system has the following defects:
[0004] 1. The cross-sectional shape of the cell flow channel or the microsphere flow channel is set, and the flow rate of different cells or different microspheres may be different when flowing in the flow channel with liquid as the carrier. Taking cells as an example, some cells are relatively close to the wall of the flow channel, so the movement speed is relatively slow, and some cells are relatively far from the wall of the flow channel, so the movement speed is relatively fast. The interval time from the detection of cells by the detection module to the closing of the microvalve is fixed, and the interval time from the detection of cells by the detection module to the closing of the microvalve is fixed. This increases the stopping range of different cells. In order to compensate for this factor, the buffer pressure for flushing cells needs to be increased, but this will increase the particle size of the droplet after pairing, reduce the collision probability of mRNA released by cells and microspheres, and affect the capture of cell mRNA by microspheres.
[0005] 2. The cells or microspheres that have entered the pairing flow channel are easily affected by the flow of liquid, and there is a risk of being flushed out of the pairing flow channel. Taking cells as an example, when a single cell enters the pairing flow channel and the microsphere has not entered, the liquid in the microsphere flow channel needs to continue to flow and pass through the pairing space. The disturbance of the liquid may flush away the single cell in the pairing space, resulting in only microspheres in the encapsulated droplet.
[0006] 3. The encapsulated droplet is easy to contact with the flow channel wall of the oil liquid flow channel, and the droplet is easy to break under the action of the wetting effect. Utility model content
[0007] The utility model discloses at least solve one of the prior art technical problems. For this purpose, the utility model provides a microfluidic system for target object pairing.
[0008] According to the microfluidic system for target object pairing in the first embodiment of the utility model, the microfluidic system includes first flow channel, second flow channel, oil liquid flow channel, buffer liquid flow channel and pairing flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel and the buffer liquid flow channel are all communicated to the pairing flow channel, the first flow channel is used for the first liquid containing the first target object passes through, the second flow channel is used for the second liquid containing the second target object passes through;
[0009] The microfluidic system further includes pairing microvalve arranged corresponding to the pairing flow channel, first microvalve arranged corresponding to the first flow channel, second microvalve arranged corresponding to the second flow channel and buffer liquid microvalve arranged corresponding to the buffer liquid flow channel, the pairing microvalve is used to control the on-off of the pairing flow channel, the first microvalve is used to control the on-off of the first flow channel, the second microvalve is used to control the on-off of the second flow channel, and the buffer liquid microvalve is used to control the on-off of the buffer liquid flow channel;
[0010] The microfluidic system is configured to: when a single first target object and a single second target object exist in the pairing flow channel, the first microvalve and the second microvalve are in the closed state, and the pairing microvalve and the buffer liquid microvalve are in the open state, so that the buffer liquid in the buffer liquid flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil liquid in the oil liquid flow channel to form a droplet;
[0011] Wherein, the first flow channel includes the first microvalve segment corresponding to the first microvalve, and the first flow segment distinguished from the first microvalve segment, the upper side inner wall surface and the lower side inner wall surface of the first flow segment are mutually parallel planes;
[0012] And / or, the second flow channel includes the second microvalve segment corresponding to the second microvalve, and the second flow segment distinguished from the second microvalve segment, the upper side inner wall surface and the lower side inner wall surface of the second flow segment are mutually parallel planes.
[0013] The microfluidic system for target object pairing according to the embodiments of the utility model has at least the following beneficial effects:
[0014] The embodiment reduces the distance difference between different target objects and the upper inner wall surface of the first flow section, thereby reducing the flow rate difference caused by the distance difference, and further reducing the interception range of the target objects, so that the pressure of the buffer solution and the volume of the liquid can be correspondingly reduced, thereby helping to improve the success rate of capture.
[0015] In other embodiments of the present application, the cross section of the first flow section is rectangular, and / or the cross section of the second flow section is rectangular.
[0016] In other embodiments of the present application, the width of the first flow section is 50-150 microns, and / or the width of the second flow section is 50-150 microns.
[0017] In other embodiments of the present application, the upper inner wall surface of the first micro valve section is provided as an arc surface protruding away from the first micro valve, and / or the upper inner wall surface of the second micro valve section is provided as an arc surface protruding away from the second micro valve.
[0018] In other embodiments of the present application, the cross section of the first micro valve section is semicircular, and / or the cross section of the second micro valve section is semicircular.
[0019] In other embodiments of the present application, the maximum height of the oil flow channel is 80-200 microns.
[0020] In other embodiments of the present application, the microfluidic system further comprises a first sheath flow channel, which is in communication with the first flow channel and is used to input a first sheath flow wrapping the first liquid into the first flow channel.
[0021] And / or, the microfluidic system further comprises a second sheath flow channel, which is in communication with the second flow channel and is used to input a second sheath flow wrapping the second liquid into the second flow channel.
[0022] In other embodiments of the present application, the microfluidic system further comprises a waste liquid flow channel and a waste liquid micro valve corresponding to the waste liquid flow channel, the waste liquid flow channel is in communication with the pairing flow channel, and the waste liquid micro valve is used to control the opening and closing of the waste liquid flow channel.
[0023] When the pairing micro valve is in a closed state and the first micro valve and the waste liquid micro valve are in an open state, the liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel.
[0024] and / or, when the pair micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, the liquid in the second flow channel can flow out through the pair flow channel and the waste liquid flow channel.
[0025] In other embodiments of the present application, along the flow direction of the buffer in the pair flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system further comprises a first stop micro valve for controlling the opening and closing of the pair flow channel located between the waste liquid flow channel and the first flow channel.
[0026] In other embodiments of the present application, the microfluidic system is configured to switch the first stop micro valve from an open state to a closed state when the single second target object is located in the pair flow channel, and when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pair micro valve, the buffer micro valve and the first stop micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form droplets.
[0027] In other embodiments of the present application, along the flow direction of the buffer in the pair flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are sequentially arranged, and the microfluidic system is configured to switch the second micro valve from an open state to a closed state when the single first target object is located in the pair flow channel, so that the single second target object is located in the pair flow channel.
[0028] In other embodiments of the present application, the microfluidic system is configured to switch the first stop micro valve from an open state to a closed state when the single second target object is located in the pair flow channel, and when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pair micro valve, the buffer micro valve and the first stop micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form droplets.
[0029] In other embodiments of the present application, along the flow direction of the buffer in the pair flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are sequentially arranged, and the microfluidic system is configured to switch the second micro valve from an open state to a closed state when the single first target object is located in the pair flow channel, so that the single second target object is located in the pair flow channel.
[0030] Alternatively, the waste liquid channel, the first channel and the second channel are sequentially arranged along the flow direction of the buffer solution in the pairing channel, and the microfluidic system is configured to: when the single second target object is located in the pairing channel, the first micro valve is in the closed state again to make the single first target object located in the pairing channel;
[0031] Alternatively, the waste liquid channel, the first channel and the second channel are sequentially arranged along the flow direction of the buffer solution in the pairing channel, and the microfluidic system is configured to: when the single second target object is located in the pairing channel, the first micro valve is in the closed state again to make the single first target object located in the pairing channel;
[0032] Alternatively, the waste liquid channel, the first channel and the second channel are sequentially arranged along the flow direction of the buffer solution in the pairing channel, and the microfluidic system is configured to: when the single second target object is located in the pairing channel, the first micro valve is in the closed state again to make the single first target object located in the pairing channel.
[0033] According to the microfluidic system for target object pairing in the second embodiment of the utility model, the microfluidic system includes first channel, second channel, oil liquid channel, buffer solution channel and pairing channel, the pairing channel is communicated to the oil liquid channel, the first channel, the second channel and the buffer solution channel all are communicated to the pairing channel, the first channel is used for the first liquid containing first target object passes through, the second channel is used for the second liquid containing second target object passes through;
[0034] The microfluidic system further includes pairing micro valve corresponding to the pairing channel, first micro valve corresponding to the first channel, second micro valve corresponding to the second channel and buffer solution micro valve corresponding to the buffer solution channel, the pairing micro valve is used for controlling the on-off of the pairing channel, the first micro valve is used for controlling the on-off of the first channel, the second micro valve is used for controlling the on-off of the second channel, and the buffer solution micro valve is used for controlling the on-off of the buffer solution channel;
[0035] The microfluidic system is configured to: when there is a single first target object and a single second target object in the pairing channel, the first micro valve and the second micro valve are in the closed state, and the pairing micro valve and the buffer solution micro valve are in the open state, so that the buffer solution in the buffer solution channel sends the single first target object and the single second target object in the pairing channel into the oil liquid in the oil liquid channel to form a droplet;
[0036] Wherein, the maximum height of the oil liquid channel is 80 microns to 200 microns.
[0037] The microfluidic system for target object pairing has at least the following beneficial effects:
[0038] The maximum height of the oil liquid flow channel is arranged in the embodiment, so that the probability of liquid drops contacting the flow channel wall of the oil liquid flow channel is reduced, and the risk of liquid drop breaking is reduced.
[0039] In other embodiments of the utility model, the upper inner wall surface and the lower inner wall surface of the oil liquid flow channel are mutually parallel planes.
[0040] In other embodiments of the utility model, the cross section of the oil liquid flow channel is arranged as a rectangle.
[0041] According to the microfluidic system for target object pairing in the third embodiment of the utility model, the microfluidic system comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer liquid flow channel and a pairing flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel and the buffer liquid flow channel are all communicated to the pairing 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.
[0042] The microfluidic system further comprises a pairing micro valve arranged corresponding to the pairing flow channel, a first micro valve arranged corresponding to the first flow channel, a second micro valve arranged corresponding to the second flow channel and a buffer liquid micro valve arranged corresponding to the buffer liquid flow channel, the pairing micro valve is used for controlling the on-off of the pairing flow channel, the first micro valve is used for controlling the on-off of the first flow channel, the second micro valve is used for controlling the on-off of the second flow channel, and the buffer liquid micro valve is used for controlling the on-off of the buffer liquid flow channel.
[0043] The microfluidic system is configured to: when a single first target object and a single second target object exist in the pairing flow channel, the first micro valve and the second micro valve are in a closed state, and the pairing micro valve and the buffer liquid micro valve are in an open state, so that the buffer liquid in the buffer liquid flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil liquid in the oil liquid flow channel to form a liquid drop.
[0044] The microfluidic system further comprises a first sheath liquid flow channel, the first sheath liquid flow channel is communicated with the first flow channel, and is used for inputting a first sheath flow wrapping the first liquid to the first flow channel.
[0045] And / or, the microfluidic system further comprises a second sheath liquid flow channel, the second sheath liquid flow channel is communicated with the second flow channel, and is used for inputting a second sheath flow wrapping the second liquid to the second flow channel.
[0046] The microfluidic system for target object pairing has at least the following beneficial effects:
[0047] The sheath liquid can constrain the first liquid and / or the second liquid, so that the first liquid and / or the second liquid flow in the central region of the flow channel, and the first target object in the first liquid and / or the target object in the second liquid are prevented from being too close to the inner wall surface of the flow channel, thereby avoiding a large flow rate difference.
[0048] In other embodiments of the utility model, the first sheath liquid flow channel includes two first branch flow channels, and the two first branch flow channels are respectively communicated with the first flow channel from two sides of the first flow channel;
[0049] And / or, the second sheath liquid flow channel includes two second branch flow channels, and the two second branch flow channels are respectively communicated with the second flow channel from two sides of the second flow channel.
[0050] According to the microfluidic system for target object pairing in the fourth embodiment of the utility model, the microfluidic system includes a first flow channel, a second flow channel, an oil liquid flow channel, a buffer liquid flow channel, a pairing flow channel and a waste liquid flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel, the buffer liquid flow channel and the waste liquid flow channel are all communicated to the pairing flow channel, the first flow channel is used for passing the first liquid containing the first target object, and the second flow channel is used for passing the second liquid containing the second target object;
[0051] The microfluidic system further includes a pairing micro valve corresponding to the pairing flow channel, a first micro valve corresponding to the first flow channel, a second micro valve corresponding to the second flow channel, a buffer liquid micro valve corresponding to the buffer liquid flow channel and a waste liquid micro valve corresponding to the waste liquid flow channel, the pairing micro valve is used for controlling the on-off of the pairing flow channel, the first micro valve is used for controlling the on-off of the first flow channel, the second micro valve is used for controlling the on-off of the second flow channel, the buffer liquid micro valve is used for controlling the on-off of the buffer liquid flow channel, and the waste liquid micro valve is used for controlling the on-off of the waste liquid flow channel;
[0052] The microfluidic system is configured such that when the pairing micro valve is in a closed state and the first micro valve and the waste liquid micro valve are in an open state, liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel, when the pairing micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel, when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pairing micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet.
[0053] Wherein, along the flow direction of the buffer in the pairing flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system further comprises a first cutoff micro valve for controlling the opening and closing of the pairing flow channel located between the waste liquid flow channel and the first flow channel.
[0054] The microfluidic system for target object pairing has at least the following beneficial effects:
[0055] The first cutoff micro valve is arranged in the embodiment, so that the first target object that has entered the pairing flow channel is prevented from being driven out of the pairing flow channel by the second liquid, and thus only the second target object is ensured to be in the encapsulated droplet, thereby ensuring the encapsulation success rate.
[0056] In other embodiments of the utility model, the microfluidic system is configured such that when the single first target object is located in the pairing flow channel, the first cutoff micro valve is switched from an open state to a closed state, and when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pairing micro valve, the buffer micro valve and the first cutoff micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet.
[0057] In other embodiments of the utility model, when the single first target object does not exist in the pairing flow channel, the pairing micro valve is in a closed state and the first micro valve, the first cutoff micro valve and the waste liquid micro valve are in an open state, so that liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel;
[0058] and / or, when the single second target object is not present in the pairing flow channel, the pairing micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state to enable the liquid in the second flow channel to flow out through the pairing flow channel and the waste liquid flow channel.
[0059] According to the microfluidic system for target object pairing in the fifth embodiment of the utility model, the microfluidic system comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer liquid flow channel, a pairing flow channel and a waste liquid flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel, the buffer liquid flow channel and the waste liquid flow channel are all communicated to the pairing flow channel, the first flow channel is used for passing the first liquid containing the first target object, and the second flow channel is used for passing the second liquid containing the second target object;
[0060] The microfluidic system further comprises a pairing micro valve arranged corresponding to the pairing flow channel, a first micro valve arranged corresponding to the first flow channel, a second micro valve arranged corresponding to the second flow channel, a buffer liquid micro valve arranged corresponding to the buffer liquid flow channel and a waste liquid micro valve arranged corresponding to the waste liquid flow channel, the pairing micro valve is used for controlling the on-off of the pairing flow channel, the first micro valve is used for controlling the on-off of the first flow channel, the second micro valve is used for controlling the on-off of the second flow channel, the buffer liquid micro valve is used for controlling the on-off of the buffer liquid flow channel, and the waste liquid micro valve is used for controlling the on-off of the waste liquid flow channel;
[0061] The microfluidic system is configured to enable the liquid in the first flow channel to flow out through the pairing flow channel and the waste liquid flow channel when the pairing micro valve is in a closed state and the first micro valve and the waste liquid micro valve are in an open state, enable the liquid in the second flow channel to flow out through the pairing flow channel and the waste liquid flow channel when the pairing micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, and enable the single first target object and the single second target object in the pairing flow channel to be sent into the oil liquid in the oil liquid flow channel by the buffer liquid in the buffer liquid flow channel to form a liquid droplet when the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state and the pairing micro valve and the buffer liquid micro valve are in an open state.
[0062] Wherein, along the flow direction of the buffer liquid in the pairing flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system further comprises a second stop micro valve, and the second stop micro valve is used for controlling the on-off of the pairing flow channel located between the waste liquid flow channel and the second flow channel.
[0063] According to the microfluidic system for target object pairing provided in the embodiment of the utility model, at least the following beneficial effects are achieved.
[0064] The second cutoff micro valve is arranged in the embodiment, so that the second target object that has entered the pairing flow channel is prevented from being driven out of the pairing flow channel by the first liquid, and thus the first target object is ensured to be in the encapsulated droplet, thereby ensuring the encapsulation success rate.
[0065] In other embodiments of the utility model, the microfluidic system is configured to: when the single second target object is located in the pairing flow channel, the second cutoff micro valve is switched from the open state to the closed state, and when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in the closed state, and the pairing micro valve, the buffer liquid micro valve and the second cutoff micro valve are in the open state, so that the buffer liquid in the buffer liquid flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil liquid in the oil liquid flow channel to form a droplet.
[0066] In other embodiments of the utility model, when there is no single first target object in the pairing flow channel, the pairing micro valve is in the closed state and the first micro valve and the waste liquid micro valve are in the open state, so that the liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel;
[0067] And / or, when there is no single second target object in the pairing flow channel, the pairing micro valve is in the closed state and the second micro valve, the second cutoff micro valve and the waste liquid micro valve are in the open state, so that the liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel.
[0068] According to the sixth embodiment of the utility model for target object pairing micro -fluidic system, the micro -fluidic system includes first flow channel, second flow channel, oil liquid flow channel, buffer solution flow channel, pairing flow channel and waste liquid flow channel, the pairing flow channel is connected to the oil liquid flow channel, the first flow channel, the second flow channel, the buffer solution flow channel and the waste liquid flow channel are all connected to the pairing 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 the first liquid containing the first target object to pass through, and the second flow channel is used for the second liquid containing the second target object to pass through;The micro -fluidic system still includes the pairing micro -valve that is arranged corresponding to the pairing flow channel, the first micro -valve that is arranged corresponding to the first flow channel, the second micro -valve that is arranged corresponding to the second flow channel, the buffer solution micro -valve that is arranged corresponding to the buffer solution flow channel and the waste liquid micro -valve that is arranged corresponding to the waste liquid flow channel, the pairing micro -valve is used to control the on-off of the pairing flow channel, the first micro -valve is used to control the on-off of the first flow channel, the second micro -valve is used to control the on-off of the second flow channel, the buffer solution micro -valve is used to control the on-off of the buffer solution flow channel, and the waste liquid micro -valve is used to control the on-off of the waste liquid flow channel;
[0069] The micro -fluidic system is configured to: when the pairing micro -valve is in the closed state and the first micro -valve and the waste liquid micro -valve are in the open state, the liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel, when the pairing micro -valve is in the closed state and the second micro -valve and the waste liquid micro -valve are in the open state, the liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel, when a single first target object and a single second target object exist in the pairing flow channel, the first micro -valve, the second micro -valve and the waste liquid micro -valve are in the closed state, and the pairing micro -valve and the buffer solution micro -valve are in the open state, so that the buffer solution in the buffer solution flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil liquid in the oil liquid flow channel to form a droplet;
[0070] Wherein, along the flow direction of the buffer solution in the pairing flow channel, the waste liquid flow channel, the second flow channel and the first flow channel are sequentially arranged, and the micro -fluidic system is configured to: when the single first target object is located in the pairing flow channel, the second micro -valve is in the closed state again to make the single second target object be located in the pairing flow channel. Wherein, since the waste liquid flow channel is arranged on the side close to the second flow channel, the second liquid will flow towards the waste liquid flow channel, and will not flow towards the first flow channel that has been cut off, so that the single first target object A can be avoided to be taken away by the second liquid.
[0071] Alternatively, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence along the flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single second target object is located in the pairing flow channel, the first micro valve is in the closed state again to make the single first target object located in the pairing flow channel. Wherein, since the waste liquid flow channel is arranged on the side close to the first flow channel, the first liquid will flow towards the waste liquid flow channel, and will not flow towards the second flow channel which has been cut off, so that the single second target object B can be prevented from being taken away by the first liquid.
[0072] Alternatively, the second flow channel, the first flow channel and the waste liquid flow channel are arranged in sequence along the flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single second target object is located in the pairing flow channel, the first micro valve is in the closed state again to make the single first target object located in the pairing flow channel. Wherein, since the waste liquid flow channel is arranged on the side close to the first flow channel, the first liquid will flow towards the waste liquid flow channel, and will not flow towards the second flow channel which has been cut off, so that the single second target object B can be prevented from being taken away by the first liquid.
[0073] Alternatively, the first flow channel, the second flow channel and the waste liquid flow channel are arranged in sequence along the flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single first target object is located in the pairing flow channel, the second micro valve is in the closed state again to make the single second target object located in the pairing flow channel. Wherein, since the waste liquid flow channel is arranged on the side close to the second flow channel, the second liquid will flow towards the waste liquid flow channel, and will not flow towards the first flow channel which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0074] Additional aspects and advantages of the present application will be partially given in the following description, some of which will become apparent from the following description, or will be understood through practice of the present application. BRIEF DESCRIPTION OF DRAWINGS
[0075] The present application will be further described below in conjunction with the drawings and examples, in which:
[0076] Figure 1 It is a schematic diagram of the microfluidic system in the first embodiment of the present application;
[0077] Figure 2 It is a schematic diagram of the microfluidic system in the first embodiment of the present application; Figure 1 It is an enlarged schematic diagram of the pairing flow channel shown in the first embodiment of the present application;
[0078] Figure 3 It is a flow process schematic diagram of the microfluidic system in the first embodiment of the present application for realizing pairing of the first target object and the second target object;
[0079] Figure 4 It is the exploded view of the micro-fluidic chip in the first embodiment of the utility model;
[0080] Figure 5 It is the schematic view of the micro-valve of the micro-fluidic system in the first embodiment of the utility model in being in the open state and the closed state
[0081] Figure 6 It is the cross section schematic view of the first flow channel section in the first embodiment of the utility model;
[0082] Figure 7 It is the schematic view of showing the relative position relation of the first flow channel, the second flow channel, the waste liquid flow channel and the first stop micro-valve in the fifth embodiment of the utility model;
[0083] Figure 8 It is the schematic view of showing the relative position relation of the first flow channel, the second flow channel and the waste liquid flow channel in the sixth embodiment of the utility model;
[0084] Figure 9 It is the schematic view of showing the relative position relation of the first flow channel, the second flow channel and the waste liquid flow channel in the seventh embodiment of the utility model;
[0085] Figure 10 It is the schematic view of showing the relative position relation of the first flow channel, the second flow channel and the waste liquid flow channel in the eighth embodiment of the utility model;
[0086] Figure 11 It is the schematic view of showing the relative position relation of the first flow channel, the second flow channel and the waste liquid flow channel in the ninth embodiment of the utility model.
[0087] Reference signs:
[0088] Micro-fluidic chip 100, base layer 110, control layer 120, first micro-valve 121, diaphragm 1211, second micro-valve 122, oil micro-valve 123, buffer micro-valve 124, waste liquid micro-valve 125, matched micro-valve 126, first stop micro-valve 127, second stop micro-valve 128, flow channel layer 130, first flow channel 131, first micro-valve section 1311, first flow section 1312, second flow channel 132, second micro-valve section 1321, second flow section 1322, oil flow channel 133, buffer flow channel 134, fourth part 1341, waste liquid flow channel 135, matched flow channel 136, first sheath flow channel 137, first branch flow channel 1371, second sheath flow channel 138, second branch flow channel 1381, first micro-valve control flow channel 139;
[0089] Single first target object A;
[0090] Single second target object B;
[0091] Droplet C;
[0092] First detection light D
[0093] Second detection light E. DETAILED DESCRIPTION
[0094] Embodiments of the present application will be described in detail below, examples of which are shown in the drawings, wherein the same or similar notations represent the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by reference to the drawings are exemplary only, and are for the purpose of explanation only and are not to be taken as limiting the present application.
[0095] In the description of the present application, it should be understood that, if the orientation description, such as up, down, front, back, left, right and other indications of the orientation or positional relationship is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as limiting the present application.
[0096] In the description of the present application, the meaning of several is more than one, the meaning of multiple is more than two, greater than, less than, more than and the like are understood as not including the number, above, below, within and the like are understood as including the number. If the first, second is described for the purpose of distinguishing technical features, it cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or the order of indicated technical features.
[0097] In the description of the present application, unless otherwise explicitly limited, the words such as setting, installing, connecting and the like should be understood in a broad sense, and the skilled in the art can reasonably determine the specific meaning of the above words in the present application in combination with the specific content of the technical solution.
[0098] In the description of the present application, the description of the terms "one embodiment", "some embodiments", "illustrative embodiment", "example", "specific example" or "some examples" means that the specific features, structures, materials or characteristics described in combination with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics can be combined in any one or more embodiments or examples in a suitable manner.
[0099] The first embodiment of the present application proposes a microfluidic system for target object pairing, with reference 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 pairing flow channel 136. The first flow channel 131 is used for passing the first liquid containing the first target object, the second flow channel 132 is used for passing the second liquid containing the second target object, the buffer flow channel 134 is used for passing the buffer, the oil flow channel 133 is used for passing the oil liquid which does not mix with the first liquid, the second liquid and the buffer, and the pairing flow channel 136 is used for stopping the single first target object A and the single second target object B. The pairing flow channel 136 is connected to the oil flow channel 133, and the first flow channel 131, the second flow channel 132 and the buffer flow channel 134 are all connected to the pairing flow channel 136. In this embodiment, the first target object is a cell, and the second target object is a microsphere. It can be understood by those skilled in the art that the first target object can be a cell, and the second target object can also be a cell.
[0100] The microfluidic system of this embodiment further includes a plurality of microvalves, specifically, a pairing microvalve 126 corresponding to the pairing flow channel 136, a first microvalve 121 corresponding to the first flow channel 131, a second microvalve 122 corresponding to the second flow channel 132, and a buffer microvalve 124 corresponding to the buffer flow channel 134. The pairing microvalve 126 is used for controlling the opening and closing of the pairing flow channel 136, the first microvalve 121 is used for controlling the opening and closing of the first flow channel 131, the second microvalve 122 is used for controlling the opening and closing of the second flow channel 132, and the buffer microvalve 124 is used for controlling the opening and closing of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the first microvalve 121 controls the opening and closing of the first flow channel 131, which means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a free-flowing state, and the first 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.
[0101] For ease of understanding, first refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are described as follows: Figure 4As shown, the microfluidic system comprises a microfluidic chip 100, which comprises a base layer 110, a control layer 120 and a flow channel layer 130 arranged 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). The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste flow channel 135 and the pairing flow channel 136 as described above. The control layer 120 has the first micro valve 121, the second micro valve 122, the buffer micro valve 124, the waste micro valve 125 and the pairing micro valve 126, and a micro valve control flow channel corresponding to each micro valve. For reference Figure 5 Taking the first micro valve 121 as an example, the first micro valve 121 comprises a diaphragm 1211 arranged between the first flow channel 131 (specifically, the first micro valve section 1311 described below) and the first micro valve control flow channel 139. When the first micro valve 121 is in the open state as shown in a of Figure 5 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first micro valve section 1311. When the diaphragm 1211 is driven by the liquid or gas in the first micro valve control flow channel 139 to protrude towards the first flow channel 131 to be in the closed state as shown in b of Figure 5 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first micro valve section 1311, and the first liquid cannot pass through the first micro valve section 1311. In the embodiment shown in Figure 5 , the upper inner wall surface of the first micro valve section 1311 is arranged as an arc surface facing away from the protrusion of the first micro valve 121, specifically a semicircular arc surface, which facilitates the close fit with the diaphragm 1211 protruding towards the first micro valve section 1311, thereby ensuring the cutoff effect. The second micro valve section 1321 of the second flow channel 132 can be understood with reference to the first micro valve section 1311.
[0102] In this embodiment, with reference to Figure 3When a single first target A and a single second target B exist in the pairing flow channel 136, the first micro valve 121 and the second micro valve 122 are in the closed state (the micro valves are filled with black to indicate the closed state), and the pairing micro valve 126 and the buffer micro valve 124 are in the open state (the micro valves are filled with gray to indicate the open state), at this time, the buffer in the buffer flow channel 134 can send the single first target A and the single second target B in the pairing flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet C, in this way, the single first target A and the single second target B are temporarily stored in the separate pairing flow channel 136, and the separate buffer flow channel 134 is provided, and the single first target A and the single second target B are pushed into the oil liquid by the buffer, without the need to push the single first target A and the single second target B by the first liquid and the second liquid, so that the first flow channel 131 and the second flow channel 132 can be kept in the cutoff state during packaging, so that other first targets and / or other second targets can be completely avoided to enter the droplet C, which is beneficial to improve the success rate of packaging and reduce cell loss caused by multiple packaging.
[0103] On this basis, referring to Figure 1 , the first flow channel 131 includes a first micro valve section 1311 corresponding to the first micro valve 121, and a first flow section 1312 different from the first micro valve section 1311, wherein the first flow section 1312 mainly functions as a flow passage for the first liquid, and the first micro valve section 1311 functions as a flow passage for the first liquid in addition to the function of cooperating with the first micro valve 121 to achieve shut-off control. For example, as viewed in a direction perpendicular to the microfluidic chip 100, the first micro valve section 1311 covers the first micro valve 121, and along the flow direction of the first liquid, the upstream (connected to the inlet portion of the first liquid) and the downstream (connected to the portion of the pairing flow channel 136) of the first micro valve section 1311 are both the first flow section 1312. In the embodiment, the first micro valve section 1311 and the first flow section 1312 are different in cross-sectional shape, and the first micro valve section 1311 can be provided as a flow channel with an arc-shaped upper wall surface as shown in Figure 5 , and the first flow section 1312 has a upper inner wall surface and a lower inner wall surface which are parallel planes as shown in Figure 6 . The purpose of this design is that if the first flow section 1312 adopts Figure 5The flow channel shown has an arc-shaped upper wall surface, and the flow rates of different cells or different microspheres in the flow channel may be different when they flow in the flow channel with liquid as the carrier. Taking cells as an example, some cells are located at the center of the flow channel, and thus are far away from the upper wall surface and flow at a relatively fast speed. Some cells are located at the side of the flow channel, and thus are close to the upper wall surface and flow at a relatively slow speed. The interval time from when the detection module detects the cells to when the micro valve is closed is fixed, which increases the stopping range of different cells in the pairing flow channel 136. In order to ensure that the cells stopped at different positions can be filled into the oil flow channel 133, the pressure of the buffer used to flush the cells needs to be increased, which in turn increases the particle size of the droplets after pairing, reduces the collision probability of the mRNA released by the cells and the microspheres, and affects the capture of the mRNA of the cells by the microspheres. The upper inner wall surface and the lower inner wall surface of the present embodiment are parallel planes, which reduces the distance difference between different cells and the upper inner wall surface, thereby reducing the flow rate difference caused by the distance difference, and further reducing the stopping range of the cells. The pressure of the buffer and the volume of the liquid can be correspondingly reduced, thereby helping to improve the success rate of capture.
[0104] In some other embodiments, the second flow channel 132 includes a second micro valve segment 1321 corresponding to the second micro valve 122, and a second flow segment 1322 different from the second micro valve segment 1321. The upper inner wall surface and the lower inner wall surface of the second flow segment 1322 are parallel planes. The structure and function of the second micro valve segment 1321 and the second flow segment 1322 of the present embodiment can be understood with reference to the first micro valve segment 1311 and the first flow segment 1312.
[0105] On the basis of the first embodiment, in some embodiments of the present application, Figure 6 The cross section of the first flow segment 1312 is rectangular, which can reduce the difficulty of manufacturing the flow channel while ensuring that the upper inner wall surface and the lower inner wall surface of the first flow segment 1312 are parallel to each other.
[0106] In some other embodiments, the cross section of the second flow segment 1322 is rectangular, which can reduce the difficulty of manufacturing 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.
[0107] On the basis of the first embodiment, in some embodiments of the utility model, the width of the first flow section 1312 is 50-150 microns, that is, the first flow section 1312 has enough space in the width direction, which can avoid the first target object being too close to the left and right inner side of the first flow section 1312 to affect the flow rate, thereby reducing the flow rate difference between different first target objects caused by the distance difference, and further improving the success rate of pairing. Exemplarily, the width of the first flow section 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.
[0108] In some other embodiments, the width of the second flow section 1322 is 50-150 microns, that is, the second flow section 1322 has enough space in the width direction, which can avoid the second target object being too close to the left and right inner side of the second flow section 1322 to affect the flow rate, thereby reducing the flow rate difference between different second target objects caused by the distance difference, and further improving the success rate of pairing. Exemplarily, the width of the second flow section 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.
[0109] On the basis of the first embodiment, in some embodiments of the utility model, the maximum height of the oil flow channel 133 is 80-200 microns. In the actual packaging process, the packaged droplets may come into 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 pulled apart with the flow of oil. By setting the maximum height of the oil flow channel 133, the probability of the droplets contacting the flow channel wall of the oil flow channel 133 can be reduced, 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.
[0110] In some specific embodiments, the upper inner wall surface of the oil flow channel 133 can be an arc surface similar to the first micro valve 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.
[0111] On the basis of the first embodiment, in some embodiments of the utility model, refer to Figure 1The microfluidic system further comprises a first sheath liquid flow channel 137 in communication with the first flow channel 131 for inputting a first sheath flow wrapping the first liquid into the first flow channel 131. In this embodiment, the sheath liquid is arranged to constrain the first liquid, so that the first liquid flows in the central region of the flow channel, and the first target objects in the first liquid are prevented from being too close to the inner wall surface of the flow channel. It should be noted that in combination with the aforementioned arrangement of the upper and lower inner wall surfaces of the first flow section 1312 as parallel planes, the flow rates of different first target objects can be further stabilized.
[0112] In some specific embodiments, with reference to Figure 1 The first sheath liquid flow channel 137 comprises two first branch flow channels 1371 in communication with the first flow channel 131 from two sides of the first flow channel 131 respectively, so that the first liquid can be constrained between the two sheath flows.
[0113] In some other embodiments, with reference to Figure 1 The microfluidic system further comprises a second sheath liquid flow channel 138 in communication with the second flow channel 132 for inputting a second sheath flow wrapping the second liquid into the second flow channel 132. In this embodiment, the sheath liquid is arranged to constrain the second liquid, so that the second liquid flows in the central region of the flow channel, and the second target objects in the second liquid are prevented from being too close to the inner wall surface of the flow channel. It should be noted that in combination with the aforementioned arrangement of the upper and lower inner wall surfaces of the second flow section 1322 as parallel planes, the flow rates of different second target objects can be further stabilized.
[0114] In some specific embodiments, with reference to Figure 1 The second sheath liquid flow channel 138 comprises two second branch flow channels 1381 in communication with the second flow channel 132 from two sides of the second flow channel 132 respectively, so that the second liquid can be constrained between the two sheath flows.
[0115] On the basis of the first embodiment, with reference to Figures 1 to 3In some embodiments of the utility model, the microfluidic system further comprises a waste liquid flow channel 135, the waste liquid flow channel 135 is used for discharging the first liquid and the second liquid, and the waste liquid flow channel 135 is communicated with the matching flow channel 136. In addition, the microfluidic system further comprises a waste liquid micro valve 125 arranged corresponding to the waste liquid flow channel 135, and the waste liquid micro valve 125 is used for controlling the on-off of the waste liquid flow channel 135. When the matching micro valve 126 is in the closed state and the first micro valve 121 and the waste liquid micro valve 125 are in the open state, the first liquid in the first flow channel 131 can flow out through the matching flow channel 136 and the waste liquid flow channel 135. In other embodiments, when the matching micro valve 126 is in the closed state and the second micro valve 122 and the waste liquid micro valve 125 are in the open state, the liquid in the second flow channel 132 can flow out through the 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 gradually approach and reach the matching flow channel 136 following the flow of the first liquid and the second liquid respectively, and when the first target object and the second target object have not reached the matching flow channel 136, the first flow channel 131 and the second flow channel 132 will continue to discharge the first liquid and the second liquid, which need to be discharged as waste liquid.
[0116] In combination with the above structure, in combination with Figures 1 to 3 The control of each micro valve is described as follows:
[0117] The matching process buffer micro valve 124 and the matching micro valve 126 are closed, the first micro valve 121, the second micro valve 122 and the waste liquid micro valve 125 are opened, and the first liquid and the second liquid are discharged through the matching flow channel 136 and the waste liquid flow channel 135 (for example, a in Figure 3 When a single first target object is identified, the first micro valve 121 is closed, and the single first target object is stopped in the matching flow channel 136 (for example, b in Figure 3 When a single second target object is identified, the second micro valve 122 is closed, and the single second target object is stopped in the matching flow channel 136 (for example, c in Figure 3 When the single first target object and the single second target object are both stopped in the matching flow channel 136, the waste liquid micro valve 125 is closed.
[0118] The encapsulation process, when the first micro valve 121, the second micro valve 122 and the waste liquid micro valve 125 are closed, the buffer micro valve 124 and the matching micro valve 126 are opened, and the buffer sends the single first target object and the single second target object in the matching flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet (for example, d in Figure 3 .
[0119] When the microfluidic system further comprises the waste liquid flow channel 135, in some embodiments of the utility model, referring to Figure 1 , Figure 2 , along the flow direction of the buffer in the matching flow channel 136, for exampleFigure 1 、 Figure 2 In the top-to-bottom direction, 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 comprises a first stop micro valve 127, which is used to control the opening and closing of the paired flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131. Exemplarily, the paired flow channel 136 is located between the waste liquid flow channel 135 and the first flow channel 131 in the top-to-bottom direction. Figure 1 、 Figure 2 In the top-to-bottom direction, the first stop micro valve 127 is arranged on the paired flow channel 136 between the waste liquid flow channel 135 and the first flow channel 131. In this embodiment, by arranging the first stop micro valve 127, it can be avoided that the first target object that has entered the paired flow channel 136 is driven out of the paired flow channel 136 by the second liquid, so that only the second target object is left in the encapsulated droplet, thereby ensuring the success rate of encapsulation.
[0120] In some specific embodiments, in combination with Figure 1 、 Figure 2 It is understood that the microfluidic system is configured such that when a single first target object A is located in the paired flow channel 136, the first stop micro valve 127 is switched from an open state to a closed state, at this time the paired flow channel 136 where the single first target object A is located is isolated from the paired flow channel 136 where the second liquid flows through the first stop micro valve 127, and the flow of the second liquid will not drive the first target object.
[0121] The microfluidic system is further configured such that when there is a single first target object A and a single second target object B in the paired flow channel 136, the first micro valve 121, the second micro valve 122 and the waste liquid micro valve 125 are in a closed state, and the paired micro valve 126, the buffer micro valve 124 and the first stop micro valve 127 are in an open state, so that the buffer in the buffer flow channel 134 sends the single first target object A and the single second target object B in the paired flow channel 136 into the oil in the oil flow channel 133 to form a droplet C.
[0122] In this embodiment, by controlling the opening and closing of the first stop micro valve 127, the first target object can be saved in the paired flow channel 136 during the pairing process, and the pairing and encapsulation of the first target object and the second target object will not be affected.
[0123] It should be noted that before the first stop micro valve 127 is in the closed state, the second micro valve 122 can be in the open state at all times, so that the second liquid is continuously discharged from the waste liquid flow channel 135 (i.e., no capture of the second target object B is performed), or the second micro valve 122 can be in the closed state first, and then opened after the first stop micro valve 127 is in the closed state, and then the subsequent capture of the single second target object B is performed.
[0124] When the microfluidic system also includes a waste liquid channel 135, in some other embodiments of the present invention, refer to Figure 7 Along the flow direction of the buffer solution within the paired flow channel 136, for example Figure 7 In the top-to-bottom direction, the waste liquid flow channel 135 is located between the first flow channel 131 and the second flow channel 132. Based on this, the microfluidic system also includes a second shut-off microvalve 128, which controls the opening and closing of the paired flow channel 136 located between the waste liquid flow channel 135 and the second flow channel 132. For example, along... Figure 7 From top to bottom, the second shut-off microvalve 128 is disposed on the mating channel 136 between the waste liquid channel 135 and the second channel 132. In this embodiment, by setting the second shut-off microvalve 128, the second target object that has entered the mating channel 136 can be driven out of the mating channel 136 by the first liquid, so that the encapsulated droplet contains only the first target object, thereby ensuring the success rate of encapsulation.
[0125] In some specific embodiments, combined with Figure 7 To understand this, the microfluidic system is configured such that when a single second target object B is located in the paired flow channel 136, the second shut-off microvalve 128 switches from the open state to the closed state. At this time, the paired flow channel 136 where the single second target object B is located is isolated from the paired flow channel 136 through which the first liquid flows by through the second shut-off microvalve 128, and the flow of the first liquid will not carry the second target object.
[0126] The microfluidic system is also configured such that when a single first target A and a single second target B are present in the paired channel 136, the first microvalve 121, the second microvalve 122, and the waste liquid microvalve 125 are closed, while the paired microvalve 126, the buffer microvalve 124, and the second shut-off microvalve 128 are open, so that the buffer in the buffer channel 134 delivers the single first target A and the single second target B in the paired channel 136 into the oil in the oil channel 133 to form droplets C.
[0127] In this embodiment, by controlling the on / off state of the second cut-off microvalve 128, the second 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 and second target objects.
[0128] In other embodiments, the microfluidic system may also omit the shut-off microvalve, see reference. Figure 8 Along the flow direction of the buffer solution within the paired flow channel 136, for example Figure 8In the embodiment shown in FIG. 13, the waste liquid flow channel 135, the first flow channel 131 and the second flow channel 132 are sequentially arranged from top to bottom. In this case, the microfluidic system is configured such that, after the single first target object A is located in the pairing flow channel 136, the second microvalve 122 is in the closed state to enable the single second target object B to be located in the pairing flow channel 136, i.e., the embodiment requires that the single first target object A be first ensured to be located in the pairing flow channel 136 (at this time, the first microvalve 121 is already in the closed state), and then the single second target object B is enabled to be located in the pairing flow channel 136. For example, the second microvalve 122 is in the closed state before the single first target object A is located in the pairing flow channel 136, the second microvalve 122 is then opened after the single first target object A is located in the pairing flow channel 136, and the second microvalve 122 is then closed after the detection module detects the single second target object B, so that the single second target object B can be stopped in the pairing flow channel 136.
[0129] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the second flow channel 132, the second liquid will flow towards the waste liquid flow channel 135 and will not flow towards the first flow channel 131 which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0130] In other embodiments, with reference to Figure 9 , along the flow direction of the buffer in the pairing flow channel 136, for example Figure 9 In the embodiment shown in FIG. 13, the waste liquid flow channel 135, the first flow channel 131 and the second flow channel 132 are sequentially arranged from top to bottom. In this case, the microfluidic system is configured such that, after the single first target object A is located in the pairing flow channel 136, the second microvalve 122 is in the closed state to enable the single second target object B to be located in the pairing flow channel 136, i.e., the embodiment requires that the single first target object A be first ensured to be located in the pairing flow channel 136 (at this time, the first microvalve 121 is already in the closed state), and then the single second target object B is enabled to be located in the pairing flow channel 136. For example, the second microvalve 122 is in the closed state before the single first target object A is located in the pairing flow channel 136, the second microvalve 122 is then opened after the single first target object A is located in the pairing flow channel 136, and the second microvalve 122 is then closed after the detection module detects the single second target object B, so that the single second target object B can be stopped in the pairing flow channel 136.
[0131] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the second flow channel 132, the second liquid will flow towards the waste liquid flow channel 135 and will not flow towards the first flow channel 131 which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0132] In other embodiments, with reference to Figure 10 , along the flow direction of the buffer in the pairing flow channel 136, for exampleFigure 10 In the direction from top to bottom, the second flow channel 132, the first flow channel 131 and the waste liquid flow channel 135 are sequentially arranged. On this basis, the microfluidic system is configured to: when the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is in the closed state again to make the single first target object A located in the pairing flow channel 136, that is, the embodiment needs to ensure that the single second target object N is located in the pairing flow channel 136 first (at this time, the second micro valve 122 is already in the closed state), and then make the single first target object A located in the pairing flow channel 136. For example, the first micro valve 121 is in the closed state before the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is opened again when the single second target object B is located in the pairing flow channel 136, and the first micro valve 121 is closed again when the detection module detects the single first target object A, so that the single first target object A can stop in the pairing flow channel 136.
[0133] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the first flow channel 131, the first liquid will flow towards the waste liquid flow channel 135 and will not flow towards the second flow channel 132 which has been cut off, so that the single second target object B can be prevented from being taken away by the first liquid.
[0134] In other embodiments, with reference to Figure 11 , in the direction of the flow of the buffer in the pairing flow channel 136, for example Figure 11 In the direction from top to bottom, the first flow channel 131, the second flow channel 132 and the waste liquid flow channel 135 are sequentially arranged. On this basis, the microfluidic system is configured to: when the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is in the closed state again to make the single second target object B located in the pairing flow channel 136, that is, the embodiment needs to ensure that the single first target object A is located in the pairing flow channel 136 first (at this time, the first micro valve 121 is already in the closed state), and then make the single second target object B located in the pairing flow channel 136. For example, the second micro valve 122 is in the closed state before the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is opened again when the single first target object A is located in the pairing flow channel 136, and the second micro valve 122 is closed again when the detection module detects the single second target object B, so that the single second target object B can stop in the pairing flow channel 136.
[0135] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the second flow channel 132, the second liquid will flow towards the waste liquid flow channel 135 and will not flow towards the first flow channel 131 which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0136] On the basis of the first embodiment, the microfluidic system of some embodiments of the utility model still includes detection module, detection module is configured to identify single first target object A in first flow channel 131, wherein, when detection module identifies single first target object A, first micro valve 121 and matching micro valve 126 are all in closed state to make single first target object A keep in matching flow channel 136. It needs to be explained that, in this embodiment, first micro valve 121 in closed state specifically refers to switching from open state to closed state, and matching micro valve 126 in closed state specifically refers to keeping in closed state.
[0137] 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 micro valve 122 and the matching micro valve 126 are both in a closed state to keep the single second target object B in the matching flow channel 136. It needs to be explained that, in this embodiment, the second micro valve 122 in the closed state specifically refers to switching from the open state to the closed state, and the matching micro valve 126 in the closed state specifically refers to keeping in the closed state.
[0138] In some specific embodiments, the detection module is specifically a visual detection module, which includes a camera and a controller. The controller is configured to control the camera to take images. When the camera takes images, the controller is further configured to identify the single first target object A and the single second target object B based on the images.
[0139] In 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 first detection light D to the first flow channel 131, the first detection light D can excite first fluorescence after irradiating the single first target object A, and the first light detection device can receive the first fluorescence excited by the single first target object A. For example, the first light source is a laser, and the first light detection device is a photomultiplier tube. When the photomultiplier tube receives the first fluorescence emitted by the single first target object A, the photomultiplier tube can convert the light signal into an electrical signal and then transmit the electrical signal to the controller. The controller is further configured to control the second light source to emit second detection light E to the second flow channel 132, the second detection light E can excite second fluorescence after irradiating the single second target object B, and when the second light detection device detects the second fluorescence, the controller identifies the single second target object B.
[0140] In some embodiments, the detection module is 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 object A passes through the first detection electrode, the first detection electrode generates a corresponding signal. The controller is configured to identify the single first target object A based on the signal detected by the first detection electrode. Specifically, the first detection electrode includes a positive electrode and a negative electrode arranged side by side. When the microfluidic system includes the 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.
[0141] The second embodiment of the utility model discloses a kind of microfluidic systems for target object pairing, referring to Figures 1 to 3 , including first flow channel 131, second flow channel 132, oil liquid flow channel 133, buffer flow channel 134 and pairing flow channel 136, wherein, first flow channel 131 is for containing first target object's first liquid passage, second flow channel 132 is for containing second target object's second liquid passage, buffer flow channel 134 is for buffer passage, oil liquid flow channel 133 is for not with first liquid, second liquid, buffer oil liquid that melts passes, pairing flow channel 136 is for single first target object A and single second target object B stay. Pairing flow channel 136 is connected to oil liquid flow channel 133, first flow channel 131, second flow channel 132 and buffer flow channel 134 are all connected to pairing flow channel 136. In this embodiment, with first target object as cell, second target object is microsphere and is explained, and person skilled in the art can understand that, first target object can be cell, and second target object can also be cell.
[0142] The microfluidic system of the embodiment further comprises a plurality of microvalves, specifically, a pairing microvalve 126 corresponding to the pairing flow channel 136, a first microvalve 121 corresponding to the first flow channel 131, a second microvalve 122 corresponding to the second flow channel 132, and a buffer microvalve 124 corresponding to the buffer flow channel 134, wherein the pairing microvalve 126 is used to control the opening and closing of the pairing flow channel 136, the first microvalve 121 is used to control the opening and closing of the first flow channel 131, the second microvalve 122 is used to control the opening and closing of the second flow channel 132, and the buffer microvalve 124 is used to control the opening and closing of the buffer flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the first microvalve 121 controls the opening and closing of the first flow channel 131, which means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a free-flowing state, and the first 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.
[0143] For ease of understanding, first refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve will be described. As shown in Figure 4 , the microfluidic system comprises a microfluidic chip 100, and the microfluidic chip 100 comprises a base layer 110, a control layer 120, and a flow channel layer 130 which are sequentially stacked. The base layer 110 can be made of glass, and the control layer 120 and the flow channel layer 130 can be made of polydimethylsiloxane (PDMS). The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste flow channel 135, and the pairing flow channel 136. The control layer 120 has the first microvalve 121, the second microvalve 122, the buffer microvalve 124, the waste microvalve 125, and the pairing microvalve 126, as well as a microvalve control flow channel corresponding to each microvalve. Refer to Figure 5 , taking the first microvalve 121 as an example, the first microvalve 121 comprises a diaphragm 1211 arranged 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 the open state as shown in Figure 5 a, 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 flow channel 139 to protrude towards the first flow channel 131 to be in the closed state as shown in Figure 5 b, 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. In Figure 5In the shown embodiment, the upper inner wall surface of the first micro valve section 1311 is provided as an arc surface protruding away from the first micro valve 121, specifically a semicircular arc surface, facilitating the adhesion to the diaphragm 1211 protruding towards the first micro valve section 1311, thereby ensuring the cutoff effect. The second micro valve section 1321 of the second flow channel 132 can be understood with reference to the first micro valve section 1311.
[0144] In the present embodiment, with reference to steps c to d of Figure 3 When there is a single first target object A and a single second target object B in the pairing flow channel 136, the first micro valve 121 and the second micro valve 122 are in the closed state (the micro valves are filled with black to indicate that they are in the closed state), and the pairing micro valve 126 and the buffer micro valve 124 are in the open state (the micro valves are filled with gray to indicate that they are in the open state), at this time, the buffer in the buffer flow channel 134 can send the single first target object A and the single second target object B in the pairing flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet C. In this way, the single first target object A and the single second target object B are temporarily stored in the separate pairing flow channel 136, and the separate buffer flow channel 134 is provided, and the single first target object A and the single second target object B are pushed into the oil liquid by the buffer, without the need to push the single first target object A and the single second target object B by the first liquid and the second liquid, so that the first flow channel 131 and the second flow channel 132 can be kept in the closed state during packaging, thereby completely avoiding other first target objects and / or other second target objects from entering the droplet C, which is beneficial to improve the success rate of packaging and reduce cell loss caused by multiple packaging.
[0145] On this basis, the maximum height of the oil liquid flow channel 133 in the present embodiment is 80 microns to 200 microns. In the actual packaging process, the packaged droplet may come into contact with the flow channel wall of the oil liquid flow channel 133 in a large area, causing the droplet to adhere to the flow channel wall and be pulled apart with the flow of the oil liquid. By setting the maximum height of the oil liquid flow channel 133, the probability of the droplet contacting the flow channel wall of the oil liquid flow channel 133 can be reduced, thereby reducing the risk of droplet breakage. For example, the maximum height of the oil liquid 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.
[0146] On the basis of the second embodiment, in some embodiments of the present application, the upper inner wall surface and the lower inner wall surface of the oil liquid flow channel 133 are parallel planes, which can further reduce the probability of the droplet contacting the flow channel wall of the oil liquid flow channel 133. In some specific embodiments, the cross section of the oil liquid flow channel 133 is provided as a rectangle, facilitating the preparation of the flow channel.
[0147] The utility model discloses a third embodiment discloses a kind of microfluidic system for target object pairing, refer to Figures 1 to 3 Including first flow passage 131, second flow passage 132, oil liquid flow passage 133, buffer flow passage 134 and pairing flow passage 136, wherein, first flow passage 131 is for containing first liquid by first target object, second flow passage 132 is for containing second liquid by second target object, buffer flow passage 134 is for buffer through, oil liquid flow passage 133 is for not with first liquid, second liquid, buffer phase fusion oil liquid through, pairing flow passage 136 is for single first target object A and single second target object B stay.Pairing flow passage 136 is connected to oil liquid flow passage 133, and first flow passage 131, second flow passage 132 and buffer flow passage 134 are all connected to pairing flow passage 136.In this embodiment, with first target object as cell, second target object is microsphere and is explained, and those skilled in the art can understand that first target object can be cell, and second target object can also be cell.
[0148] The microfluidic system of the embodiment further includes a plurality of microvalves, specifically including pairing microvalve 126 arranged corresponding to pairing flow passage 136, first microvalve 121 arranged corresponding to first flow passage 131, second microvalve 122 arranged corresponding to second flow passage 132 and buffer microvalve 124 arranged corresponding to buffer flow passage 134, wherein, pairing microvalve 126 is used to control the on-off of pairing flow passage 136, first microvalve 121 is used to control the on-off of first flow passage 131, second microvalve 122 is used to control the on-off of second flow passage 132, and buffer microvalve 124 is used to control the on-off of buffer flow passage 134, with first flow passage 131 and first microvalve 121 as an example, the on-off of first flow passage 131 by the so-called first microvalve 121 controller is that: first microvalve 121 has opening state and closing state, when first microvalve 121 is in opening state, first flow passage 131 is in free state, and first liquid can flow in first flow passage 131, when first microvalve 121 is in closing state, first flow passage 131 is in cut-off state, and first liquid cannot flow in first flow passage 131.
[0149] For ease of understanding, first refer to Figure 4 、 Figure 5 The overall structure of microfluidic system and the specific structure of microvalve are described, such as Figure 4As shown, the microfluidic system comprises a microfluidic chip 100, which comprises a base layer 110, a control layer 120 and a flow channel layer 130 arranged 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). The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste flow channel 135 and the pairing flow channel 136 as described above. The control layer 120 has the first micro valve 121, the second micro valve 122, the buffer micro valve 124, the waste micro valve 125 and the pairing micro valve 126, and a micro valve control flow channel corresponding to each micro valve. For reference Figure 5 Taking the first micro valve 121 as an example, the first micro valve 121 comprises a diaphragm 1211 arranged between the first flow channel 131 (specifically, the first micro valve section 1311 described below) and the first micro valve control flow channel 139. When the first micro valve 121 is in the open state as shown in a of Figure 5 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first micro valve section 1311. When the diaphragm 1211 is driven by the liquid or gas in the first micro valve control flow channel 139 to protrude towards the first flow channel 131 to be in the closed state as shown in b of Figure 5 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first micro valve section 1311, and the first liquid cannot pass through the first micro valve section 1311. In the embodiment shown in Figure 5 , the upper inner wall surface of the first micro valve section 1311 is arranged as an arc surface facing away from the protrusion of the first micro valve 121, specifically a semicircular arc surface, which facilitates the close fit with the diaphragm 1211 protruding towards the first micro valve section 1311, thereby ensuring the cutoff effect. The second micro valve section 1321 of the second flow channel 132 can be understood with reference to the first micro valve section 1311.
[0150] In this embodiment, with reference to Figure 3When there is a single first target A and a single second target B in the pairing flow channel 136, the first micro valve 121 and the second micro valve 122 are in the closed state (the micro valve is filled with black to indicate that it is in the closed state), and the pairing micro valve 126 and the buffer micro valve 124 are in the open state (the micro valve is filled with gray to indicate that it is in the open state), at this time, the buffer in the buffer flow channel 134 can send the single first target A and the single second target B in the pairing flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet C, so that the single first target A and the single second target B are temporarily stored in the separate pairing flow channel 136, and the separate buffer flow channel 134 is provided, and the single first target A and the single second target B are pushed into the oil liquid by the buffer, without the need to push the single first target A and the single second target B by the first liquid and the second liquid, so that the first flow channel 131 and the second flow channel 132 can be kept in the cutoff state during packaging, so that other first targets and / or other second targets can be completely avoided to enter the droplet C, which is beneficial to improve the success rate of packaging and reduce cell loss caused by multiple packaging.
[0151] On this basis, the microfluidic system in the embodiment further includes a first sheath flow channel 137 in communication with the first flow channel 131 for inputting a first sheath flow wrapping the first liquid into the first flow channel 131. By setting the sheath liquid to constrain the first liquid, the first liquid can flow in the central region of the flow channel in the embodiment, so as to avoid that the first targets in the first liquid are too close to the inner wall of the flow channel, thereby causing a large flow rate difference between different first targets.
[0152] In some specific embodiments, referring to Figure 1 The first sheath flow channel 137 includes two first branch flow channels 1371 in communication with the first flow channel 131 from both sides of the first flow channel 131, so as to constrain the first liquid between the two sheath flows.
[0153] In some specific embodiments, referring to Figure 1 The microfluidic system further includes a second sheath flow channel 138 in communication with the second flow channel 132 for inputting a second sheath flow wrapping the second liquid into the second flow channel 132. By setting the sheath liquid to constrain the second liquid, the second liquid can flow in the central region of the flow channel in the embodiment, so as to cause a large flow rate difference between different second targets.
[0154] In some specific embodiments, referring to Figure 1The second sheath liquid flow channel 138 includes two second branch flow channels 1381, which are respectively communicated with the second flow channel 132 from two sides of the second flow channel 132, so that the second liquid can be constrained between the two sheath flows.
[0155] The fourth embodiment of the utility model discloses a microfluidic system for target object pairing, referring to Figures 1 to 3 , including first flow channel 131, second flow channel 132, oil liquid flow channel 133, buffer solution flow channel 134 and pairing flow channel 136, wherein, first flow channel 131 is used for containing first liquid that has first target object passes through, second flow channel 132 is used for containing second liquid that has second target object passes through, buffer solution flow channel 134 is used for buffer solution to pass through, oil liquid flow channel 133 is used for not with first liquid, second liquid, buffer solution melts oil liquid to pass through, pairing flow channel 136 is used for single first target object A and single second target object B to stay.Pairing flow channel 136 is communicated to oil liquid flow channel 133, and first flow channel 131, second flow channel 132 and buffer solution flow channel 134 are all communicated to pairing flow channel 136.In this embodiment, with first target object as cell, second target object is microsphere and is explained, and those skilled in the art can understand that first target object can be cell, and second target object can also be cell.
[0156] The microfluidic system of the embodiment further includes a plurality of microvalves, specifically including a pairing microvalve 126 corresponding to the pairing flow channel 136, a first microvalve 121 corresponding to the first flow channel 131, a second microvalve 122 corresponding to the second flow channel 132, and a buffer solution microvalve 124 corresponding to the buffer solution flow channel 134. The pairing microvalve 126 is used to control the on-off of the pairing 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 buffer solution flow channel 134. Taking the first flow channel 131 and the first microvalve 121 as an example, the first microvalve 121 controls the on-off of the first flow channel 131, which means that the first microvalve 121 has an open state and a closed state. When the first microvalve 121 is in the open state, the first flow channel 131 is in a free-flowing state, and the first 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.
[0157] For ease of understanding, first refer to Figure 4 , Figure 5 The overall structure of the microfluidic system and the specific structure of the microvalve are described as follows Figure 4As shown, the microfluidic system comprises a microfluidic chip 100, which comprises a base layer 110, a control layer 120 and a flow channel layer 130 arranged 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). The flow channel layer 130 has the first flow channel 131, the second flow channel 132, the oil flow channel 133, the buffer flow channel 134, the waste flow channel 135 and the pairing flow channel 136 as described above. The control layer 120 has the first micro valve 121, the second micro valve 122, the buffer micro valve 124, the waste micro valve 125 and the pairing micro valve 126, and a micro valve control flow channel corresponding to each micro valve. For reference Figure 5 Taking the first micro valve 121 as an example, the first micro valve 121 comprises a diaphragm 1211 arranged between the first flow channel 131 (specifically, the first micro valve section 1311 described below) and the first micro valve control flow channel 139. When the first micro valve 121 is in the open state as shown in a of Figure 5 , the diaphragm 1211 is in a horizontal state, and the first liquid can pass through the first micro valve section 1311. When the diaphragm 1211 is driven by the liquid or gas in the first micro valve control flow channel 139 to protrude towards the first flow channel 131 to be in the closed state as shown in b of Figure 5 , the diaphragm 1211 is close to the inner wall of the first flow channel 131 to cut off the first micro valve section 1311, and the first liquid cannot pass through the first micro valve section 1311. In the embodiment shown in Figure 5 , the upper inner wall surface of the first micro valve section 1311 is arranged as an arc surface facing away from the protrusion of the first micro valve 121, specifically a semicircular arc surface, which facilitates the close fit with the diaphragm 1211 protruding towards the first micro valve section 1311, thereby ensuring the cutoff effect. The second micro valve section 1321 of the second flow channel 132 can be understood with reference to the first micro valve section 1311.
[0158] In this embodiment, with reference to Figure 3When a single first target A and a single second target B exist in the pairing flow channel 136, the first micro valve 121 and the second micro valve 122 are in the closed state (the micro valves are filled with black to indicate that they are in the closed state), and the pairing micro valve 126 and the buffer micro valve 124 are in the open state (the micro valves are filled with gray to indicate that they are in the open state), at this time, the buffer in the buffer flow channel 134 can send the single first target A and the single second target B in the pairing flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet C, in this way, the single first target A and the single second target B are temporarily stored in the separate pairing flow channel 136, and the separate buffer flow channel 134 is provided, and the single first target A and the single second target B are pushed into the oil liquid by the buffer, without the need to push the single first target A and the single second target B by the first liquid and the second liquid, so that the first flow channel 131 and the second flow channel 132 can be kept in the cutoff state during packaging, thereby completely avoiding other first targets and / or other second targets from entering the droplet C, which is beneficial to improve the success rate of packaging and reduce cell loss caused by multiple packaging.
[0159] In addition, the microfluidic system further comprises a waste liquid flow channel 135 for discharging the first liquid and the second liquid, the waste liquid flow channel 135 being in communication with the pairing flow channel 136. In addition, the microfluidic system further comprises a waste liquid micro valve 125 arranged corresponding to the waste liquid flow channel 135, the waste liquid micro valve 125 being used for controlling the opening and closing of the waste liquid flow channel 135. When the pairing micro valve 126 is in the closed state and the first micro valve 121 and the waste liquid micro valve 125 are in the open state, the first liquid in the first flow channel 131 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135. In other embodiments, when the pairing micro valve 126 is in the closed state and the second micro valve 122 and the waste liquid micro valve 125 are in the open state, the liquid in the second flow channel 132 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135. It should be noted that the first target and the second target will gradually approach and reach the pairing flow channel 136 along with the flow of the first liquid and the second liquid, and when the first target and the second target have not reached the pairing flow channel 136, the first flow channel 131 and the second flow channel 132 will continue to discharge the first liquid and the second liquid, which need to be discharged as waste liquid.
[0160] On this basis, with reference to Figure 1 、 Figure 2 , along the flow direction of the buffer in the pairing flow channel 136, for example Figure 1 、 Figure 2In the top-to-bottom direction, the waste liquid flow channel 135 in the embodiment is located between the first flow channel 131 and the second flow channel 132. The microfluidic system further comprises a first stop micro valve 127 for controlling the opening and closing of a matched flow channel 136 between the waste liquid flow channel 135 and the first flow channel 131. Exemplarily, the matched flow channel 136 is located between the first flow channel 131 and the waste liquid flow channel 135. Figure 1 、 Figure 2 In the top-to-bottom direction, the first stop micro valve 127 is arranged on the matched flow channel 136 between the waste liquid flow channel 135 and the first flow channel 131. By arranging the first stop micro valve 127, the embodiment can avoid the first target object that has entered the matched flow channel 136 from being washed out of the matched flow channel 136 by the second liquid, so that only the second target object is left in the encapsulated droplet, thereby ensuring the success rate of encapsulation. It should be noted that when the first target object is a target object such as a tumor cell, the number of the target object in the sample is small, and the cost is also high. By arranging the first stop micro valve 127, the embodiment can also reduce the waste of the first target object.
[0161] On the basis of the fourth embodiment, some embodiments of the utility model can be understood in combination with Figure 1 、 Figure 2 The microfluidic system is configured to: when a single first target object A is located in the matched flow channel 136, the first stop micro valve 127 is switched from an open state to a closed state, at which time the matched flow channel 136 in which the single first target object A is located is isolated from the matched flow channel 136 through which the second liquid flows by the first stop micro valve 127, and the flow of the second liquid will not carry the first target object.
[0162] The microfluidic system is further configured to: when there is a single first target object A and a single second target object B in the matched flow channel 136, the first micro valve 121, the second micro valve 122 and the waste liquid micro valve 125 are in a closed state, and the matched micro valve 126, the buffer micro valve 124 and the first stop micro valve 127 are in an open state, so that the buffer in the buffer flow channel 134 sends the single first target object A and the single second target object B in the matched flow channel 136 into the oil in the oil flow channel 133 to form a droplet C.
[0163] In the embodiment, by controlling the opening and closing of the first stop micro valve 127, the first target object can be saved in the matched flow channel 136 during the pairing waiting process, and the pairing and encapsulation of the first target object and the second target object will not be affected.
[0164] It should be noted that before the first shut-off microvalve 127 is closed, the second microvalve 122 can remain open, allowing the second liquid to continuously discharge from the waste liquid channel 135 (i.e., without capturing the second target B). Alternatively, the second microvalve 122 can be closed initially, and then opened again after the first shut-off microvalve 127 is closed to capture the subsequent single second target B.
[0165] Based on the fourth embodiment, in some embodiments of this utility model, when there is no single first target A in the paired flow channel 136, the paired micro valve 126 is in a closed state and the first micro valve 121, the first shut-off micro valve 127 and the waste liquid micro valve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the paired flow channel 136 and the waste liquid flow channel 135, thereby causing the first target to flow into the paired flow channel 136.
[0166] In other embodiments, when there is no single second target object B in the paired flow channel 136, the paired micro valve 126 is in a closed state and the second micro valve 122 and the waste liquid micro valve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the paired flow channel 136 and the waste liquid flow channel 135, thereby causing the second target object to flow into the paired flow channel 136.
[0167] The fifth embodiment of this utility model discloses a microfluidic system for target pairing, which differs from the fourth embodiment in that: the fourth embodiment is provided with a first shut-off microvalve 127, which is used to control the opening and closing of the pairing channel 136 located between the waste liquid channel 135 and the first channel 131; this embodiment is provided with a second shut-off microvalve 128, which is used to control the opening and closing of the pairing channel 136 located between the waste liquid channel 135 and the second channel 132. For example, along... Figure 7 From top to bottom, the second shut-off microvalve 128 is disposed on the mating channel 136 between the waste liquid channel 135 and the second channel 132. In this embodiment, by setting the second shut-off microvalve 128, the second target object that has entered the mating channel 136 can be driven out of the mating channel 136 by the first liquid, so that the encapsulated droplet contains only the first target object, thereby ensuring the success rate of encapsulation.
[0168] In some specific embodiments, combined with Figure 7 To understand this, the microfluidic system is configured such that when a single second target object B is located in the paired flow channel 136, the second shut-off microvalve 128 switches from the open state to the closed state. At this time, the paired flow channel 136 where the single second target object B is located is isolated from the paired flow channel 136 through which the first liquid flows by through the second shut-off microvalve 128, and the flow of the first liquid will not carry the second target object.
[0169] The microfluidic system is further configured to: when a single first target object A and a single second target object B exist in the pairing flow channel 136, the first micro valve 121, the second micro valve 122 and the waste liquid micro valve 125 are in a closed state, and the pairing micro valve 126, the buffer liquid micro valve 124 and the second stop micro valve 128 are in an open state, so that the buffer liquid in the buffer liquid flow channel 134 sends the single first target object A and the single second target object B in the pairing flow channel 136 into the oil liquid in the oil liquid flow channel 133 to form a droplet C.
[0170] In the embodiment, by controlling the opening and closing of the second stop micro valve 128, the second target object can be stored in the pairing flow channel 136 during the pairing waiting process, and the pairing and packaging of the first target object and the second target object are not affected.
[0171] On the basis of the fifth embodiment, in some embodiments of the utility model, when the single first target object A does not exist in the pairing flow channel 136, the pairing micro valve 126 is in a closed state and the first micro valve 121 and the waste liquid micro valve 125 are in an open state, so that the liquid in the first flow channel 131 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135, and then the first target object flows to the pairing flow channel 136.
[0172] In other embodiments, when the single second target object B does not exist in the pairing flow channel 136, the pairing micro valve 126 is in a closed state and the second micro valve 122, the second stop micro valve 128 and the waste liquid micro valve 125 are in an open state, so that the liquid in the second flow channel 132 can flow out through the pairing flow channel 136 and the waste liquid flow channel 135, and then the second target object flows to the pairing flow channel 136.
[0173] The sixth embodiment of the utility model discloses a microfluidic system for target object pairing, which is different from the fourth embodiment in that the waste liquid flow channel 135 in the fourth embodiment is located between the first flow channel 131 and the second flow channel 132, and is provided with a first stop micro valve 127, the first stop micro valve 127 is used for controlling the opening and closing of the pairing flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131, and in the embodiment, no stop micro valve is arranged, but the single first target object A is maintained through the positional relationship of the flow channel.
[0174] Specifically, referring to Figure 8 , along the flow direction of the buffer liquid in the pairing flow channel 136, for example Figure 8In the direction from top to bottom, the waste liquid flow channel 135, the second flow channel 132 and the first flow channel 131 are sequentially arranged. On this basis, the microfluidic system is configured such that when the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is in the closed state again to enable the single second target object B to be located in the pairing flow channel 136, that is, the embodiment needs to ensure that the single first target object A is located in the pairing flow channel 136 first (at this time, the first micro valve 121 is already in the closed state), and then enable the single second target object B to be located in the pairing flow channel 136. For example, the second micro valve 122 is in the closed state before the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is opened again after the single first target object A is located in the pairing flow channel 136, and the second micro valve 122 is closed again after the detection module detects the single second target object B, so that the single second target object B can be stopped in the pairing flow channel 136.
[0175] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the second flow channel 132, the second liquid will flow towards the waste liquid flow channel 135 and will not flow towards the first flow channel 131 which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0176] The seventh embodiment of the utility model discloses a kind of microfluidic systems for target object pairing, which is different from the fourth embodiment in that: waste liquid flow channel 135 in the fourth embodiment is located between first flow channel 131 and second flow channel 132, and is provided with first cut-off micro valve 127, and first cut-off micro valve 127 is used to control the on-off of pairing flow channel 136 between waste liquid flow channel 135 and first flow channel 131, and in the embodiment, cut-off micro valve is not arranged, but the position relationship of flow channel is used to realize the retention of single first target object A.
[0177] Specifically, referring to Figure 9 , along the flow direction of buffer in pairing flow channel 136, for example Figure 9 In the direction from top to bottom, the waste liquid flow channel 135, the first flow channel 131 and the second flow channel 132 are sequentially arranged. On this basis, the microfluidic system is configured such that when the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is in the closed state again to enable the single first target object A to be located in the pairing flow channel 136, that is, the embodiment needs to ensure that the single second target object N is located in the pairing flow channel 136 first (at this time, the second micro valve 122 is already in the closed state), and then enable the single first target object A to be located in the pairing flow channel 136. For example, the first micro valve 121 is in the closed state before the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is opened again after the single second target object B is located in the pairing flow channel 136, and the first micro valve 121 is closed again after the detection module detects the single first target object A, so that the single first target object A can be stopped in the pairing flow channel 136.
[0178] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the first flow channel 131, the first liquid will flow towards the waste liquid flow channel 135 and will not flow towards the second flow channel 132 which has been cut off, so that the single second target object B can be prevented from being taken away by the first liquid.
[0179] The eighth embodiment of the utility model discloses a microfluidic system for target object pairing, which is different from the fourth embodiment in that the waste liquid flow channel 135 in the fourth embodiment is located between the first flow channel 131 and the second flow channel 132, and is provided with a first cut-off micro valve 127, and the first cut-off micro valve 127 is used for controlling the on-off of a pairing flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131, and in the embodiment, no cut-off micro valve is arranged, but the single first target site A is kept through the positional relationship of the flow channels.
[0180] Specifically, referring to Figure 10 , along the flow direction of the buffer in the pairing flow channel 136, for example Figure 10 From top to bottom, the second flow channel 132, the first flow channel 131 and the waste liquid flow channel 135 are sequentially arranged. On this basis, the microfluidic system is configured such that when the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is in the closed state to make the single first target object A located in the pairing flow channel 136, that is, the embodiment needs to first ensure that the single second target object N is located in the pairing flow channel 136 (at this time, the second micro valve 122 is already in the closed state), and then make the single first target object A located in the pairing flow channel 136. For example, the first micro valve 121 is in the closed state before the single second target object B is located in the pairing flow channel 136, the first micro valve 121 is opened again after the single second target object B is located in the pairing flow channel 136, and the first micro valve 121 is closed again after the detection module detects the single first target object A, so that the single first target object A can be stopped in the pairing flow channel 136.
[0181] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the first flow channel 131, the first liquid will flow towards the waste liquid flow channel 135 and will not flow towards the second flow channel 132 which has been cut off, so that the single second target object B can be prevented from being taken away by the first liquid.
[0182] The ninth embodiment of the utility model discloses a microfluidic system for target object pairing, which is different from the fourth embodiment in that: the waste liquid flow channel 135 in the fourth embodiment is located between the first flow channel 131 and the second flow channel 132, and is provided with a first stop micro valve 127, the first stop micro valve 127 is used for controlling the on-off of the pairing flow channel 136 located between the waste liquid flow channel 135 and the first flow channel 131, no stop micro valve is arranged in the embodiment, and the single first target site A is kept through the positional relationship of the flow channel.
[0183] Specifically, referring to Figure 11 , along the flow direction of the buffer in the pairing flow channel 136, for example Figure 11 From top to bottom, the first flow channel 131, the second flow channel 132 and the waste liquid flow channel 135 are sequentially arranged. On this basis, the microfluidic system is configured: when the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is in the closed state to make the single second target object B located in the pairing flow channel 136, that is, the embodiment needs to ensure that the single first target object A is located in the pairing flow channel 136 first (at this time, the first micro valve 121 has been in the closed state), and then make the single second target object B located in the pairing flow channel 136, for example, the second micro valve 122 is in the closed state before the single first target object A is located in the pairing flow channel 136, the second micro valve 122 is opened again when the single first target object A is located in the pairing flow channel 136, and the second micro valve 122 is closed again when the detection module detects the single second target object B, so that the single second target object B can stop in the pairing flow channel 136.
[0184] In the embodiment, since the waste liquid flow channel 135 is arranged on the side close to the second flow channel 132, the second liquid will flow towards the waste liquid flow channel 135 and will not flow towards the first flow channel 131 which has been cut off, so that the single first target object A can be prevented from being taken away by the second liquid.
[0185] The embodiments of the utility model are described in detail above in combination with the drawings, but the utility model is not limited to the above-mentioned embodiments, and various changes can be made within the knowledge range possessed by ordinary skilled persons in the technical field without departing from the purpose of the utility model. In addition, the embodiments of the utility model and the features in the embodiments can be combined with each other without conflict.
Claims
1. A microfluidic 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 pairing flow channel, the pairing flow channel is communicated to the oil flow channel, the first flow channel, the second flow channel and the buffer flow channel are all communicated to the pairing 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 pairing micro valve arranged corresponding to the pairing flow channel, a first micro valve arranged corresponding to the first flow channel, a second micro valve arranged corresponding to the second flow channel and a buffer micro valve arranged corresponding to the buffer flow channel, the pairing micro valve is used for controlling the opening and closing of the pairing flow channel, the first micro valve is used for controlling the opening and closing of the first flow channel, the second micro valve is used for controlling the opening and closing of the second flow channel, and the buffer micro valve is used for controlling the opening and closing of the buffer flow channel; The microfluidic system is configured to: when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve and the second micro valve are in a closed state, and the pairing micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet; The first flow channel comprises a first micro valve section arranged corresponding to the first micro valve, and a first flow section different from the first micro valve section, the upper side inner wall surface and the lower side inner wall surface of the first flow section are mutually parallel planes; The second flow channel comprises a second micro valve section arranged corresponding to the second micro valve, and a second flow section different from the second micro valve section, the upper side inner wall surface and the lower side inner wall surface of the second flow section are mutually parallel planes.
2. The microfluidic system for target pairing of claim 1, wherein, The cross section of the first flow section is rectangular, and / or the cross section of the second flow section is rectangular.
3. The microfluidic system for target pairing of claim 2, wherein, The width of the first flow section is 50 microns to 150 microns, and / or the width of the second flow section is 50 microns to 150 microns.
4. The microfluidic system for target pairing of claim 1, wherein, The upper side inner wall surface of the first micro valve section is arranged as an arc surface protruding away from the first micro valve, and / or the upper side inner wall surface of the second micro valve section is arranged as an arc surface protruding away from the second micro valve.
5. The microfluidic system for target pairing of claim 4, wherein, The cross section of the first micro valve section is semicircular, and / or the cross section of the second micro valve section is semicircular.
6. The microfluidic system for target pairing of claim 1, wherein, The maximum height of the oil flow channel is 80 microns to 200 microns.
7. The microfluidic system for target pairing of claim 1, wherein, The microfluidic system further comprises a first sheath flow channel, the first sheath flow channel is communicated to the first flow channel, and is used for inputting a first sheath flow wrapping the first liquid to the first flow channel; The microfluidic system further comprises a second sheath flow channel, the second sheath flow channel is communicated to the second flow channel, and is used for inputting a second sheath flow wrapping the second liquid to the second flow channel.
8. The microfluidic system for target pairing of claim 1, wherein, 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 to the pairing flow channel, and the waste liquid micro valve is used for controlling the opening and closing of the waste liquid flow channel; wherein, when the pair micro valve is in a closed state and the first micro valve and the waste liquid micro valve are in an open state, the liquid in the first flow channel can flow out through the pair flow channel and the waste liquid flow channel; and / or, when the pair micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, the liquid in the second flow channel can flow out through the pair flow channel and the waste liquid flow channel.
9. The microfluidic system for target pairing of claim 8, wherein, The waste liquid flow channel is located between the first flow channel and the second flow channel in the flow direction of the buffer in the pair flow channel, and the microfluidic system further comprises a first stop micro valve for controlling the opening and closing of the pair flow channel located between the waste liquid flow channel and the first flow channel.
10. The microfluidic system for target pairing of claim 9, wherein, The microfluidic system is configured to switch the first stop micro valve from an open state to a closed state when the single first target object is located in the pair flow channel, and when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pair micro valve, the buffer micro valve and the first stop micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form a droplet.
11. The microfluidic system for target pairing of claim 8, wherein, The waste liquid flow channel is located between the first flow channel and the second flow channel in the flow direction of the buffer in the pair flow channel, and the microfluidic system further comprises a second stop micro valve for controlling the opening and closing of the pair flow channel located between the waste liquid flow channel and the second flow channel.
12. The microfluidic system for target pairing of claim 11, wherein, The microfluidic system is configured to switch the second stop micro valve from an open state to a closed state when the single second target object is located in the pair flow channel, and when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pair micro valve, the buffer micro valve and the second stop micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form a droplet.
13. The microfluidic system for target pairing of claim 8, wherein, The waste liquid flow channel, the second flow channel and the first flow channel are arranged in sequence in the flow direction of the buffer in the pair flow channel, and the microfluidic system is configured to switch the second micro valve to a closed state again so that the single second target object is located in the pair flow channel when the single first target object is located in the pair flow channel; Alternatively, the waste liquid flow channel, the first flow channel and the second flow channel are arranged in sequence in the flow direction of the buffer in the pair flow channel, and the microfluidic system is configured to switch the first micro valve to a closed state again so that the single first target object is located in the pair flow channel when the single second target object is located in the pair flow channel; Alternatively, the second flow channel, the first flow channel and the waste liquid flow channel are sequentially arranged along the flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single second target is located in the pairing flow channel, the first micro valve is in the closed state again to make the single first target located in the pairing flow channel. Alternatively, the first flow channel, the second flow channel and the waste liquid flow channel are sequentially arranged along the flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single first target is located in the pairing flow channel, the second micro valve is in the closed state again to make the single second target located in the pairing flow channel.
14. A microfluidic system for target pairing, characterized by, The microfluidic system comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer flow channel and a pairing flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel and the buffer flow channel are all communicated to the pairing flow channel, the first flow channel is used for passing the first liquid containing the first target, and the second flow channel is used for passing the second liquid containing the second target. The microfluidic system further comprises a pairing micro valve corresponding to the pairing flow channel, a first micro valve corresponding to the first flow channel, a second micro valve corresponding to the second flow channel and a buffer micro valve corresponding to the buffer flow channel, the pairing micro valve is used for controlling the opening and closing of the pairing flow channel, the first micro valve is used for controlling the opening and closing of the first flow channel, the second micro valve is used for controlling the opening and closing of the second flow channel, and the buffer micro valve is used for controlling the opening and closing of the buffer flow channel. The microfluidic system is configured to: when there is a single first target and a single second target in the pairing flow channel, the first micro valve and the second micro valve are in the closed state, and the pairing micro valve and the buffer micro valve are in the open state, so that the buffer in the buffer flow channel sends the single first target and the single second target in the pairing flow channel into the oil liquid in the oil liquid flow channel to form a droplet. The maximum height of the oil liquid flow channel is 80 microns to 200 microns.
15. The microfluidic system for target pairing of claim 14, wherein, The upper side inner wall surface and the lower side inner wall surface of the oil liquid flow channel are mutually parallel planes.
16. The microfluidic system for target pairing of claim 15, wherein, The cross section of the oil liquid flow channel is rectangular.
17. A microfluidic system for target pairing, characterized by, The microfluidic system comprises a first flow channel, a second flow channel, an oil liquid flow channel, a buffer flow channel and a pairing flow channel, the pairing flow channel is communicated to the oil liquid flow channel, the first flow channel, the second flow channel and the buffer flow channel are all communicated to the pairing flow channel, the first flow channel is used for passing the first liquid containing the first target, and the second flow channel is used for passing the second liquid containing the second target. The microfluidic system further comprises a pairing micro valve corresponding to the pairing flow channel, a first micro valve corresponding to the first flow channel, a second micro valve corresponding to the second flow channel, and a buffer micro valve corresponding to the buffer flow channel, the pairing micro valve being used to control the opening and closing of the pairing flow channel, the first micro valve being used to control the opening and closing of the first flow channel, the second micro valve being used to control the opening and closing of the second flow channel, and the buffer micro valve being used to control the opening and closing of the buffer flow channel; The microfluidic system is configured to: when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve and the second micro valve are in a closed state, and the pairing micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet; The microfluidic system further comprises a first sheath flow channel, which is in communication with the first flow channel and is used to input a first sheath flow wrapping the first liquid into the first flow channel. The microfluidic system further comprises a second sheath flow channel, which is in communication with the second flow channel and is used to input a second sheath flow wrapping the second liquid into the second flow channel.
18. The microfluidic system for target pairing of claim 17, wherein, The first sheath flow channel comprises two first branch flow channels, which are in communication with the first flow channel from both sides of the first flow channel, respectively. The second sheath flow channel comprises two second branch flow channels, which are in communication with the second flow channel from both sides of the second flow channel, respectively.
19. A microfluidic system for target pairing, characterized by, 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 being in communication with the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel, and the waste flow channel all being in communication with the pairing flow channel, the first flow channel being used for the first liquid containing a first target object to pass through, and the second flow channel being used for the second liquid containing a second target object to pass through; The microfluidic system further comprises a pairing micro valve corresponding to the pairing flow channel, a first micro valve corresponding to the first flow channel, a second micro valve corresponding to the second flow channel, a buffer micro valve corresponding to the buffer flow channel, and a waste micro valve corresponding to the waste flow channel, the pairing micro valve being used to control the opening and closing of the pairing flow channel, the first micro valve being used to control the opening and closing of the first flow channel, the second micro valve being used to control the opening and closing of the second flow channel, the buffer micro valve being used to control the opening and closing of the buffer flow channel, and the waste micro valve being used to control the opening and closing of the waste flow channel; The microfluidic system is configured to: when the pairing micro valve is in a closed state and the first micro valve and the waste liquid micro valve are in an open state, liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel; when the pairing micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel; when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pairing micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet. Wherein, along the flow direction of the buffer in the pairing flow channel, the waste liquid flow channel is located between the first flow channel and the second flow channel, and the microfluidic system further comprises a first cutoff micro valve for controlling the opening and closing of the pairing flow channel located between the waste liquid flow channel and the first flow channel.
20. The microfluidic system for target pairing of claim 19, wherein, The microfluidic system is configured to: when the single first target object is located behind the pairing flow channel, the first cutoff micro valve is switched from an open state to a closed state, and when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste liquid micro valve are in a closed state, and the pairing micro valve, the buffer micro valve and the first cutoff micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet.
21. The microfluidic system for target pairing of claim 20, wherein, When the single first target object is not present in the pairing flow channel, the pairing micro valve is in a closed state and the first micro valve, the first cutoff micro valve and the waste liquid micro valve are in an open state, so that liquid in the first flow channel can flow out through the pairing flow channel and the waste liquid flow channel; And / or, when the single second target object is not present in the pairing flow channel, the pairing micro valve is in a closed state and the second micro valve and the waste liquid micro valve are in an open state, so that liquid in the second flow channel can flow out through the pairing flow channel and the waste liquid flow channel.
22. A microfluidic system for target pairing, characterized by, 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 liquid flow channel, the pairing flow channel is communicated 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 communicated to the pairing 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 pair micro valve corresponding to the pair flow channel, a first micro valve corresponding to the first flow channel, a second micro valve corresponding to the second flow channel, a buffer micro valve corresponding to the buffer flow channel, and a waste micro valve corresponding to the waste flow channel, the pair micro valve is used to control the opening and closing of the pair flow channel, the first micro valve is used to control the opening and closing of the first flow channel, the second micro valve is used to control the opening and closing of the second flow channel, the buffer micro valve is used to control the opening and closing of the buffer flow channel, and the waste micro valve is used to control the opening and closing of the waste flow channel. The microfluidic system is configured to: when the pair micro valve is in a closed state and the first micro valve and the waste micro valve are in an open state, the liquid in the first flow channel can flow out through the pair flow channel and the waste flow channel; when the pair micro valve is in a closed state and the second micro valve and the waste micro valve are in an open state, the liquid in the second flow channel can flow out through the pair flow channel and the waste flow channel; when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste micro valve are in a closed state, and the pair micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form a droplet. Wherein, along the flow direction of the buffer in the pair flow channel, the waste flow channel is located between the first flow channel and the second flow channel, and the microfluidic system further comprises a second stop micro valve, which is used to control the opening and closing of the pair flow channel located between the waste flow channel and the second flow channel.
23. The microfluidic system for target pairing of claim 22, wherein, The microfluidic system is configured to: when the single second target object is located in the pair flow channel, the second stop micro valve is switched from an open state to a closed state, and when there is a single first target object and a single second target object in the pair flow channel, the first micro valve, the second micro valve and the waste micro valve are in a closed state, and the pair micro valve, the buffer micro valve and the second stop micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pair flow channel into the oil in the oil flow channel to form a droplet.
24. The microfluidic system for target pairing of claim 23, wherein, When there is no single first target object in the pair flow channel, the pair micro valve is in a closed state and the first micro valve and the waste micro valve are in an open state, so that the liquid in the first flow channel can flow out through the pair flow channel and the waste flow channel; And / or, when there is no single second target object in the pair flow channel, the pair micro valve is in a closed state and the second micro valve, the second stop micro valve and the waste micro valve are in an open state, so that the liquid in the second flow channel can flow out through the pair flow channel and the waste flow channel.
25. A microfluidic system for target pairing, characterized in that, The microfluidic system comprises a first flow channel, a second flow channel, an oil flow channel, a buffer flow channel, a pairing flow channel and a waste flow channel, the pairing flow channel is communicated to the oil flow channel, the first flow channel, the second flow channel, the buffer flow channel and the waste flow channel are all communicated 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 object, and the second flow channel is used for passing a second liquid containing a second target object; the microfluidic system further comprises a pairing micro valve arranged corresponding to the pairing flow channel, a first micro valve arranged corresponding to the first flow channel, a second micro valve arranged corresponding to the second flow channel, a buffer micro valve arranged corresponding to the buffer flow channel and a waste micro valve arranged corresponding to the waste flow channel, the pairing micro valve is used for controlling the opening and closing of the pairing flow channel, the first micro valve is used for controlling the opening and closing of the first flow channel, the second micro valve is used for controlling the opening and closing of the second flow channel, the buffer micro valve is used for controlling the opening and closing of the buffer flow channel, and the waste micro valve is used for controlling the opening and closing of the waste flow channel; The microfluidic system is configured to: when the pairing micro valve is in a closed state and the first micro valve and the waste micro valve are in an open state, the liquid in the first flow channel can flow out through the pairing flow channel and the waste flow channel, when the pairing micro valve is in a closed state and the second micro valve and the waste micro valve are in an open state, the liquid in the second flow channel can flow out through the pairing flow channel and the waste flow channel, when there is a single first target object and a single second target object in the pairing flow channel, the first micro valve, the second micro valve and the waste micro valve are in a closed state, and the pairing micro valve and the buffer micro valve are in an open state, so that the buffer in the buffer flow channel sends the single first target object and the single second target object in the pairing flow channel into the oil in the oil flow channel to form a droplet; Wherein, along the flow direction of the buffer in the pairing flow channel, the waste flow channel, the second flow channel and the first flow channel are sequentially arranged, and the microfluidic system is configured to: when the single first target object is located in the pairing flow channel, the second micro valve is in a closed state again to make the single second target object located in the pairing flow channel; Or, along the flow direction of the buffer in the pairing flow channel, the waste flow channel, the first flow channel and the second flow channel are sequentially arranged, and the microfluidic system is configured to: when the single second target object is located in the pairing flow channel, the first micro valve is in a closed state again to make the single first target object located in the pairing flow channel; Or, along the flow direction of the buffer in the pairing flow channel, the second flow channel, the first flow channel and the waste flow channel are sequentially arranged, and the microfluidic system is configured to: when the single second target object is located in the pairing flow channel, the first micro valve is in a closed state again to make the single first target object located in the pairing flow channel. Alternatively, the first flow channel, the second flow channel and the waste flow channel are arranged in sequence along a flow direction of the buffer in the pairing flow channel, and the microfluidic system is configured to: when the single first target object is located in the pairing flow channel, the second micro valve is in the closed state again to make the single second target object located in the pairing flow channel.