Microfluidic chip

Abstract

The invention provides a micro-fluidic chip. A first inlet, a second inlet and an outlet are formed in the micro-fluidic chip; the micro-fluidic chip is also provided with a first conveying flow channel, a micro-flow channel and a second conveying flow channel; the second conveying flow channel comprises a first conveying flow channel, an intersection flow channel and a second conveying flow channel which are communicated in sequence. The first inlet is communicated with the first conveying runner; the second inlet is communicated with one end of the second conveying runner, and the outlet is communicated with the other end of the second conveying runner; the number of the micro-channels is multiple, the inlet end of each micro-channel is communicated with the first conveying channel, and the outlet end of each micro-channel is communicated with the second conveying channel in an intersection manner; the multiple micro-channels are sequentially arranged between the first conveying channel and the second conveying channel. According to the micro-fluidic chip provided by the invention, the second conveying flow channel is configured to convey the continuous-phase fluid so as to convey the generated liquid drops to the outlet, so that the generation efficiency of the liquid drops and the particle size uniformity of the liquid drops are improved.

Description

Technical Field

[0001] The present application relates to microfluidic technology, and in particular to a microfluidic chip. Background Art

[0002] Microfluidics is a technology that studies and controls the behavior of fluids at the micrometer scale based on the principles of microfluidics. By precisely controlling the flow in microchannels, microfluidics enables manipulation, mixing, separation, and analysis of test samples. As the core platform of microfluidics, microfluidic chips are prepared using micromachining technology, which can manufacture micrometer-scale channels, valves, mixers, and other functional structures on the chip surface.

[0003] However, in the microfluidic chips of related technologies, the dispersed phase fluid generates droplets in the microchannels at different positions, and the droplets will accumulate at the outlet of the microchannel where the droplets are generated. The resistance generated will hinder the subsequent droplet generation and cause the generated droplets to squeeze each other, which will not only reduce the droplet generation efficiency, but also lead to droplet fusion, fewer effective droplets, and worse droplet size CV. Summary of the invention

[0004] The present invention aims to solve one of the technical problems in the related art at least to a certain extent.

[0005] An embodiment of the present application provides a microfluidic chip, characterized in that: a microfluidic chip is provided with a first inlet, a second inlet and an outlet; the microfluidic chip is also provided with a first delivery channel, a microchannel and a second delivery channel; the second delivery channel includes a first transmission channel, an intersection channel and a second transmission channel connected in sequence; wherein the first inlet is connected to the first delivery channel; the second inlet is connected to the first transmission channel, and the outlet is connected to the second transmission channel; the number of the microchannels is multiple, the inlet end of each microchannel is connected to an end of the first delivery channel away from the first inlet, and the outlet end of each microchannel is connected to the side wall of the intersection channel; the multiple microchannel outlet ends are arranged in sequence on one side wall of the intersection channel.

[0006] In one embodiment, the depth of the micro channel is smaller than the depth of the confluent channel.

[0007] In one embodiment, the microchannel and the intersection channel have a set depth difference, and the set depth difference is 15 μm to 1000 μm; or, the set depth difference is greater than the diameter of the droplets generated at the intersection.

[0008] In one embodiment, the depth of the micro channel is less than the depth of the first transport channel; and / or the depth of the first transport channel is the same as the depth of the intersection channel.

[0009] In one embodiment, the first delivery channel includes a main transmission channel and a distribution channel connected in sequence, the main transmission channel is connected to the first inlet, and one end of the main transmission channel away from the first inlet is connected to the distribution channel; the inlet end of each of the microchannels is respectively connected to the side wall of the distribution channel; the inlet ends of the microchannels are arranged in sequence along a side wall of the distribution channel.

[0010] In one embodiment, the intersection angle between the microchannel and the side wall of the intersection channel is 80-100°, and / or the intersection angle between the microchannel and the side wall of the distribution channel is 80-100°.

[0011] In one embodiment, the chip body includes a first carrier and a second carrier, and the first carrier and the second carrier are fixedly connected; wherein the first transport channel, the microchannel and the second transport channel are all arranged on a side surface of the first carrier facing the second carrier.

[0012] In one embodiment, the first inlet and the second inlet are both located on a side surface of the first carrier plate facing away from the second carrier plate, and / or the outlet is located on a side surface of the second carrier plate facing away from the first carrier plate.

[0013] In one embodiment, the second delivery channel extends to a side surface of the first carrier plate to form the outlet.

[0014] In one embodiment, the second carrier plate has a fourth through hole penetrating the second carrier plate, the outlet is located on a side surface of the second carrier plate facing away from the first carrier plate, and the fourth through hole connects the second delivery channel and the outlet.

[0015] In the microfluidic chip provided by the present application, by configuring the first delivery channel, the microchannel and the second delivery channel on the microfluidic chip, the first fluid passes through the first delivery channel and the microchannel, and generates droplets at the intersection of the microchannel and the second delivery channel, and the second delivery channel is configured to transport the second fluid of the continuous phase to transport the generated droplets to the outlet of the microfluidic chip. Therefore, after the droplets are generated, they will not accumulate inside the microfluidic chip, which solves the problems of droplet fusion, less effective droplets, and worse droplet particle size CV, and improves the droplet generation efficiency and droplet particle size uniformity. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the specific embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0017] Figure 1 A schematic diagram of the structure of a microfluidic chip provided in an embodiment of the present invention;

[0018] Figure 2 An exploded view of a microfluidic chip provided in an embodiment of the present invention;

[0019] Figure 3 for Figure 1 A schematic diagram of the microfluidic chip;

[0020] Figure 4 for Figure 1 Schematic diagram of the flow channel structure of the microfluidic chip shown;

[0021] Figure 5 for Figure 1 A schematic diagram of the structure of the second carrier plate of the microfluidic chip shown;

[0022] Figure 6 A schematic diagram of a PCR detection device provided in an embodiment of the present invention.

[0023] Description of reference numerals:

[0024] 1-first carrier plate; 111-first delivery channel; 111a-main delivery channel; 111b-distribution channel; 112-microchannel; 113-second delivery channel; 1131-droplet generation channel; 1132-droplet transport channel; 113a-first delivery channel; 113b-intersection channel; 113c-second delivery channel; 114-depth difference structure; 12-first inlet; 13-second inlet; 14-first through hole; 15-second through hole; 16-accommodating groove; 2-second carrier plate; 21-outlet; 22-fourth through hole; 501-microfluidic chip; 502-amplification unit; 503-droplet reading unit. Specific embodiments

[0025] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0027] In addition, the technical features involved in different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0028] See also Figure 1-4 The embodiment of the present application provides a microfluidic chip, which is provided with a first inlet 12, a second inlet 13 and an outlet 21; the microfluidic chip is also provided with a first delivery channel 111, a microchannel 112 and a second delivery channel 113. The first delivery channel 111 includes a main delivery channel 111a and a distribution channel 111b, and the second delivery channel 113 includes a first delivery channel 113a, a junction channel 113b and a second delivery channel 113c that are connected in sequence. The first inlet 12 is connected to the first delivery channel 111; the second inlet is connected to one end of the first delivery channel 113a; and the outlet 21 is connected to the second delivery channel 113c. There are multiple microchannels 112, the inlet end of each microchannel 112 is connected to the end of the first delivery channel 111 away from the first inlet 12, and the outlet end of each microchannel 112 is connected to the side wall of the intersection channel 113b; the outlet ends of multiple microchannels 112 are arranged in sequence on a side wall of the intersection channel 113b.

[0029] The microfluidic chip of the present application is mainly used to generate droplets. In actual use, the first fluid is delivered to the first delivery channel 111 through the first inlet 12; the second fluid is injected into the second delivery channel 113 through the second inlet, and the second fluid flows continuously along the first delivery channel 113a, the intersection channel 113b and the second delivery channel 113c in sequence, and flows out from the outlet 21; the inlet end of the microchannel 112 is connected to the end of the first delivery channel 111 away from the first inlet 12, and the outlet end of the microchannel 112 is connected to the side wall of the intersection channel 113b; the outlet ends of multiple microchannels 112 are arranged in sequence on one side wall of the intersection channel 113b. The first fluid in the first delivery channel 111 flows into the microchannel 112, and the second fluid flowing in the microchannel 112 and the intersection channel 113b intersect to generate droplets; the generated droplets are transported to the outlet 21 by the second fluid flowing in the intersection channel 113b and the second delivery channel 113c.

[0030] Specifically, in the above-mentioned microfluidic chip, the first fluid is a dispersed phase liquid, which enters the first delivery channel 111 from the first inlet 12, then enters the microchannel 112, and finally generates droplets at the intersection of the microchannel 112 and the intersection channel 113b. The second fluid is a continuous phase liquid, which continuously enters the first transmission channel 113a from the second inlet 13, and successively enters the intersection channel 113b and the second transmission channel 113c, and finally flows out from the outlet 21. Among them, a liquid driving device can be set at the first inlet 12 and the second inlet 13 to drive the first fluid and the second fluid to flow in the flow channel structure inside the microfluidic chip. It is worth noting that the "dispersed phase fluid" mentioned in the specification of this application is a fluid that is dispersed in the microfluidic chip to form droplets, and the "continuous phase fluid" is a fluid that flows continuously and uninterruptedly in the microfluidic chip. Specifically, the first fluid generates droplets at the intersection of the microchannel 112 and the intersection channel 113b, and the droplets will pass through the second transmission channel 113c together with the continuously flowing second fluid, and finally flow out from the outlet 21, thereby avoiding the risk of droplets merging due to accumulation inside the microfluidic chip and improving the uniformity of the droplet size. Specifically, by controlling the flow rate of the first fluid entering the first delivery channel 111, the droplet generation rate can be controlled; by controlling the flow rate of the second fluid entering the second delivery channel 113, the speed of droplets flowing out of the microfluidic chip can be controlled; by regulating the flow rate of the first fluid liquid entering the microchannel 112, the droplets generated in the second delivery channel 113 can be timely transmitted to the outside of the microfluidic chip, avoiding the risk of droplets accumulating inside the microfluidic chip, thereby improving the droplet generation efficiency and the droplet size uniformity.

[0031] In one embodiment, the first fluid is an aqueous phase and the second fluid is an oil phase, and the droplets obtained at this time are "water-in-oil" droplets. In this case, the aqueous phase is wrapped in the oil phase, forming tiny water droplets dispersed in the oil phase. In other embodiments, the first fluid is an oil phase and the second fluid is an aqueous phase, and the droplets obtained at this time are "oil-in-water" droplets. In this case, the oil phase is wrapped in the aqueous phase, forming tiny oil droplets dispersed in the aqueous phase. In other embodiments, the second fluid and the first fluid can also be two other immiscible liquids, such as an aqueous phase and an organic solvent, two different organic solvents, etc., which are not limited here one by one.

[0032] In the microfluidic chip of the embodiment of the present application, by configuring the first delivery channel 111, the microchannel 112 and the second delivery channel 113 on the microfluidic chip, the first fluid passes through the first delivery channel 111 and the microchannel 112, and generates droplets at the intersection of the microchannel 112 and the second delivery channel 113, and the second delivery channel 113 is configured to transport the second fluid of the continuous phase to transport the generated droplets to the outlet 21 of the microfluidic chip. Therefore, after the droplets are generated, they will not accumulate inside the microfluidic chip, which solves the problems of droplet fusion, less effective droplets, and worse droplet size CV, and improves the droplet generation efficiency and droplet size uniformity.

[0033] In one embodiment, the bottom of the microchannel 112 is flush with the bottom of the intersection channel 113b of the second delivery channel 113. Since the depth of the microchannel 112 is less than the depth of the intersection channel 113b, the bottom surface of the microchannel 112 intersects with the side wall of the intersection channel 113b, and a depth difference structure 114 is formed at the intersection. Specifically, as Figure 3 As shown, since the depth of the microchannel 112 is less than the depth of the intersection channel 113b, the bottom surface of the microchannel 112, the bottom surface of the intersection channel 113b and the side wall surface of the intersection channel (i.e., the connection surface connecting the bottom surface of the microchannel 112 and the bottom surface of the intersection channel 113b) together form a depth difference structure 114. In this embodiment, the first fluid is an oil phase, the second fluid is an aqueous phase, the density of the first fluid is less than the density of the second fluid, and at the depth difference structure 114 at the intersection, the first fluid generates a pressure gradient due to the buoyancy and the height difference of the depth difference structure 114, thereby generating droplets. In other embodiments, the first fluid may be an aqueous phase, the second fluid may be an oil phase, and at the depth difference structure at the intersection, the first fluid generates a pressure gradient due to the gravity and the height difference of the depth difference structure, thereby generating droplets. The principle is roughly the same as that of the above embodiment and will not be elaborated in detail. This droplet generation method is also called step emulsification. Droplets are generated by step emulsification. The liquid will generate a pressure gradient during the floating or falling process. This pressure gradient can drive the liquid through the depth difference structure to generate droplets.

[0034] Unlike traditional emulsification methods, pressure fluctuations within a certain range in the step emulsification method will not significantly affect the particle size of the generated droplets. This is because the step emulsification method mainly relies on the pressure gradient generated by the height difference to drive the emulsification process, rather than relying on precise control of pressure. Therefore, compared with traditional emulsification methods that require precise pressure control, the step emulsification method has lower requirements for the pressure control system and has higher fault tolerance during operation. Even if there are pressure fluctuations within a certain range, the particle size of the generated droplets can still remain relatively stable without significant deviation. This reduces the requirements for pressure control equipment and simplifies the design and operation of the system.

[0035] In one embodiment, the microchannel 112 and the intersection channel 113b have a set depth difference, and the set depth difference is 15μm to 1000μm. For example, the set depth difference can be 15μm, 25μm, 50μm, 100μm, 150μm, 200μm, 250μm, 300μm, 400μm, 500μm, 600μm, 700μm, 800μm, 900μm or 1000μm, etc. The height difference is set to be greater than the diameter of the generated droplets to avoid the generated droplets from clogging the droplet generation outlet at the intersection, further improving the droplet generation efficiency and the droplet particle size uniformity. In addition, the height difference can also be set to be less than 10 times the diameter of the generated droplets. In this way, not only is it avoided that the generated droplets clog the droplet generation outlet at the intersection, but also the amount of the second fluid is controlled, improving the use efficiency of the second fluid. More preferably, the height difference may be set to be greater than or equal to 2 times the diameter of the generated droplet and less than or equal to 3 times the diameter of the generated droplet.

[0036] Specifically, Figure 3 As shown, the intersection channel 113b can be divided into a droplet generation channel 1131 and a droplet transport channel 1132 along the depth direction of the microfluidic chip. The first fluid generates droplets in the droplet generation channel 1131 due to the buoyancy and the height difference. The droplets continue to float to the droplet transport channel 1132 (i.e., the bottom surface of the second transport channel 113) under the buoyancy, and flow to the outlet 21 in the droplet transport channel 1132. In other words, the droplet generation channel 1131 and the droplet transport channel 1132 are separated from each other, and the droplet generation process and the droplet transport process do not affect each other. It should be noted that the droplet generation channel 1131 and the droplet transport channel 1132 introduced here are not physically structured divisions. They all belong to the intersection channel 113b, and are only artificially divided for the purpose of clarifying the specification. Since the height difference is set to be greater than or equal to the diameter of the generated droplets, the droplets floating up or sinking to the bottom of the flow channel will not hinder or block the droplet generation flow channel 1131. In addition, in the case of multiple microchannels 112, the transportation process of the droplets generated by the previous microchannel on the droplet transport flow channel 1132 will not hinder or block the subsequent droplet generation flow channel 1131, thereby improving the droplet generation efficiency and the droplet particle size uniformity. However, if the depth difference is too large, the thickness of the first carrier plate 1 will inevitably be too large, otherwise the structural stability of the microfluidic chip cannot be guaranteed, which is not conducive to the miniaturization of the microfluidic chip; at the same time, the depth-to-width ratio of the microchannel obtained by the existing preparation process is limited to a certain range. If the depth difference is too large, the depth of the second transport flow channel 113 is too large, and the width of the second transport flow channel 113 is also too large, which will greatly reduce the flow resistance of the second transport flow channel 113, which is not conducive to the pressure control of the step emulsification. The depth difference between the microchannel 112 and the intersection channel 113b is preferably 50 μm to 250 μm.

[0037] In one embodiment, the depth of the second delivery channel 113 can be 20 μm to 1050 μm, and the depth of the microchannel 112 can be 5 μm to 50 μm. Exemplarily, the depth of the second delivery channel 113 can be 20 μm, 50 μm, 100 μm, 125 μm, 150 μm, 175 μm, 200 μm, 225 μm, 250 μm, 275 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm or 1050 μm, and the depth of the microchannel 112 is 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm or 50 μm. The depth of the second delivery channel 113 is preferably 100μm to 500μm, more preferably 150μm to 250μm; the depth of the microchannel 112 is preferably 10μm to 30μm, more preferably 15 to 25μm. Preferably, the depth of the first delivery channel 111 is the same as the depth of the second delivery channel 113, that is, the depth of the first delivery channel 111 is preferably 100μm to 500μm, more preferably 150μm to 250μm. At this time, there are only two depth dimensions of the microchannel inside the entire microfluidic chip, which reduces the difficulty of mold manufacturing process and injection molding, thereby reducing the difficulty of preparing the microfluidic chip. It should be noted that the channel depth of the three-section channel structure of the second delivery channel (i.e., the first delivery channel 113a, the intersection channel 113b and the second delivery channel 113c) can be set to the same value according to actual use requirements, or it can be set to different values, as long as its depth value meets the above-mentioned setting range, and it is not limited here one by one.

[0038] In one embodiment, the depth of the microchannel 112 is less than the depth of the first delivery channel 111. Since the depth of the microchannel 112 is small, when the depth of the first delivery channel 111 is the same as that of the microchannel 112, the flow resistance of the first delivery channel 111 is large, and a large pressure is required to allow the dispersed phase liquid to enter the first delivery channel 111 and flow smoothly in the first delivery channel 111. At this time, the microfluidic chip is subjected to a large force, which is easy to damage the overall structure of the microfluidic chip, which is not conducive to the service life of the microfluidic chip. By making the depth of the microchannel 112 less than the depth of the first delivery channel 111, the first fluid is easier to enter the first delivery channel 111 and flow smoothly in the first delivery channel 111, reducing the required pressure, which reduces the force applied to the microfluidic chip and is conducive to maintaining the overall structure of the microfluidic chip.

[0039] In one embodiment, the number of microchannels 112 is multiple. Preferably, the number of microchannels is greater than or equal to 2. More preferably, the number of microchannels is greater than or equal to 15. Further, the number of microchannels is 15-50. In this embodiment, multiple microchannels 112 can generate droplets at the same time, thereby improving the generation efficiency of droplets. The number of microchannels 112 can be selected according to actual needs.

[0040] Each microchannel 112 is connected to the intersection channel 113b to form an intersection, and the intersections are arranged on the side wall of the intersection channel 113b in sequence. Figure 2 and Figure 4 , multiple intersections are also arranged in sequence along the flow channel extension direction of the intersection flow channel 113b, and the first fluid generates droplets in the depth difference structure 114 at the multiple intersections, that is, it is formed in the droplet generation flow channel 1131, and due to the buoyancy or gravity, it floats or sinks into the droplet transport flow channel 1132, and is transported to the outlet 21 by the continuously flowing second fluid.

[0041] In one embodiment, the first delivery channel 111 includes a main delivery channel 111a and a distribution channel 111b that are connected in sequence. The main delivery channel 111a is connected to the first inlet 12, and the end of the main delivery channel 111a away from the first inlet 12 is connected to the distribution channel 111b. The inlet end of each microchannel 112 is respectively connected to the side wall of the distribution channel 111b. The inlet ends of the microchannels are arranged along a side wall of the distribution channel in sequence. . Specifically, the first delivery channel 111 includes a main delivery channel 111a and a distribution channel 111b that are connected to each other, and the end of the main delivery channel 111a away from the distribution channel 111b is connected to the first inlet 12, and the end of the microchannel 112 away from the intersection channel 113b is connected to the side wall of the distribution channel 111b. The end of the main delivery channel 111a away from the first inlet 12 is connected to the side wall of the distribution channel 111b. Preferably, the end of the main transmission channel 111a away from the first inlet 12 is connected to any point in the middle 1 / 3 section of the distribution channel 111b (that is, the distribution channel 111b is equally divided into 3 sections along the length direction, and the middle section is taken). More preferably, the end of the main transmission channel 111a away from the first inlet 12 is connected to the midpoint of the distribution channel 111b along the length direction. Figure 4 As shown, the inlet end of each microchannel 112 is respectively connected to the distribution channel 111b, and the inlet ends of the microchannels are sequentially arranged along the channel extension direction (i.e., the length direction) of the distribution channel 112. Through such a design, the first fluid can enter the distribution channel 111b from the main transmission channel 111a, and then flow into each microchannel 112 respectively, and form droplets at the outlet end of the microchannel 112, thereby improving the droplet generation efficiency.

[0042] In another embodiment, the first delivery channel 111 only includes the main delivery channel 111a, but does not have the distribution channel 111b. In this case, the inlet ends of each microchannel 112 overlap, that is, each microchannel 112 is connected to the same position of the end of the main delivery channel 111a in the first delivery channel 111 away from the first inlet 12. Multiple microchannels 112 converge at the same inlet end, and their outlet ends are respectively arranged along the channel extension direction of the intersection channel 113b, so the structure of the multiple microchannels 112 is radial. At this time, the first fluid flows to the same microchannel inlet end through the first delivery channel 111, and then disperses into multiple microchannels 112, and then forms droplets at the outlet end of the microchannel 112.

[0043] Furthermore, the dimensions of the multiple microchannels 112 are the same, that is, the length, width, depth, and other dimensions of the multiple microchannels 112 are the same. By limiting the dimensions of the multiple microchannels 112 to be the same, the flow resistances of different microchannels 112 are made the same, thereby ensuring that all microchannels 112 can be activated to generate droplets, and ensuring the uniformity of the particle size of the generated droplets.

[0044] In one embodiment, the spacing between the outlet ends of two adjacent microchannels 112 is greater than or equal to the diameter of the droplets generated. When multiple microchannels generate droplets at the same time, the droplets will not squeeze and accumulate each other during transportation, thereby reducing the risk of droplet fusion due to droplet accumulation in the second delivery channel 113, and improving the uniformity of the droplet particle size. In other embodiments, the multiple microchannels 112 can also be arranged in other forms, and the spacing between the multiple microchannels 112 can be equal or unequal. Furthermore, the multiple microchannels 112 are arranged in the same direction, so that the droplets generated at the outlet ends of the multiple microchannels 112 can be subjected to the same lateral shear force, thereby ensuring the uniformity of the particle size of the droplets generated.

[0045] In one embodiment, the intersection angle of the multiple microchannels 112 and the side wall of the intersection channel 113b of the second delivery channel 113 is in the range of 80-100°. Similarly, the intersection angle of the multiple microchannels 112 and the side wall of the distribution channel 111b of the first delivery channel 111 is also in the range of 80-100°. Through this intersection angle setting, during the droplet generation process, the droplets can be subjected to greater lateral shear force, thereby increasing the generation rate of the droplets. Specifically, the intersection angle of each microchannel 112 with the distribution channel 111b and the intersection channel 113b can be set to different angles or the same angle. Preferably, the intersection angle of each microchannel 112 with the first delivery channel 111 and the second delivery channel 113 is set to the same angle. At this time, the multiple microchannels are arranged in parallel, so that the droplets generated by each microchannel are subjected to the same lateral shear force, thereby ensuring the uniformity of the particle size of the generated droplets.

[0046] In one embodiment, the microchannel 112 and the distribution channel 111b intersect and communicate with each other in a vertical manner (i.e., the intersection angle between the microchannel 112 and the distribution channel 111b is 90°), and / or the microchannel 112 and the intersection channel 113b intersect and communicate with each other in a vertical manner (i.e., the intersection angle between the microchannel 112 and the intersection channel 113b is 90°). Specifically, Figure 4 As shown, the microchannel 112 intersects and connects with the intersection channel 113b in a vertical manner, so that the first fluid in the microchannel 12 enters the intersection channel 113b in a direction perpendicular to the intersection channel 113b, and generates droplets at the depth difference structure 114 at the intersection. The droplets are output to the outlet 21 along the second transmission channel 113c under the fluid driving force in the vertical direction, thereby reducing the flow resistance of the droplets. And the droplet generation direction and the droplet transportation direction are at a vertical angle, which is convenient for droplet control and operation. Further, the microchannel 112 intersects and connects with the first delivery channel 111 in a vertical manner, specifically, the microchannel 112 intersects and connects with the distribution channel 111b of the first delivery channel in a vertical manner.

[0047] In one embodiment, along the extension direction of the distribution channel 111b, the distribution channel 111b has an intermediate position, and the main transmission channel 111a is connected to the intermediate position to divide the distribution channel 111b into two branches, the two branches are respectively a first branch and a second branch, and in the extension direction perpendicular to the first transmission channel 111, the cross-sectional area of ​​the main transmission channel is greater than or equal to the sum of the cross-sectional areas of the first branch and the second branch, so that the dispersed phase liquid enters the two branches from the main transmission channel 111a. Specifically, when the depth of the main transmission channel 111a is the same as that of the two branches, the width of the main transmission channel 111a is greater than or equal to the sum of the widths of the first branch and the second branch. If the cross-sectional area of ​​the main transmission channel 111a is smaller than the sum of the cross-sectional areas of the two branches, it is not conducive to the continuous and stable entry of the dispersed phase liquid into the two branches, and thus is not conducive to the continuous and stable formation of droplets.

[0048] In one embodiment, the width of the microchannel 112 may be 10 μm-500 μm, such as 10 μm, 20 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm or 500 μm, preferably 20 μm-250 μm, more preferably 40 μm-80 μm. The width of the intersecting channel 113b can be 20μm-5mm, such as 20μm, 50μm, 75μm, 100μm, 150μm, 200μm, 300μm, 400μm, 500μm, 600μm, 700μm, 800μm, 900μm, 1mm, 2mm, 3mm, 4mm or 5mm, preferably 100μm-1mm, more preferably 250μm-500μm.

[0049] In one embodiment, the microfluidic chip includes a first carrier plate 1 and a second carrier plate 2, and the first carrier plate 1 and the second carrier plate 2 are fixedly connected. Specifically, the first carrier plate 1 and the second carrier plate 2 can be bonded and fixed by an adhesive. In one embodiment, the first delivery channel 111, the microchannel 112 and the second delivery channel 113 are all arranged on the side of the first carrier plate 1 facing the second carrier plate 2. Specifically, the first carrier plate 1 and the second carrier plate 2 are arranged opposite to each other, and the first carrier plate 1 is bonded to the surface of one side of the first carrier plate 1 having the first delivery channel 111, the microchannel 112 and the second delivery channel 113, so that the channel structure is arranged inside the microfluidic chip, and by setting the first delivery channel 111, the microchannel 112 and the second delivery channel 113 all on the first carrier plate 1, the alignment of the channels is not involved in the process of bonding the first carrier plate 1 and the second carrier plate 2, thereby reducing the difficulty of alignment, thereby reducing the difficulty of manufacturing the microfluidic chip, improving the yield of the microfluidic chip, and reducing the manufacturing cost. In another embodiment, the first carrier plate 1 and the second carrier plate 2 are both provided with a first delivery channel 111, a microchannel 112, and a second delivery channel 113, and the positions of the same channel structure on the two carrier plates correspond one to one, so in the process of bonding the first carrier plate 1 and the second carrier plate 2, the channels need to be aligned before bonding and fixing. In this embodiment, since the channel structure is distributed on the two carrier plates, compared with the solution in which the channel structure is only provided on the same carrier plate, the depth dimension of the microfluidic chip can be set smaller, thereby reducing the volume of the microfluidic chip and facilitating the miniaturization and integration of the microfluidic chip.

[0050] In one embodiment, the first inlet 12 and the second inlet 13 are both located on a side surface of the first carrier 1 away from the second carrier 2. At this time, the first carrier 1 has a first through hole 14 and a second through hole 15 penetrating the first carrier 1, the first inlet 12 is connected to one end of the first delivery channel 111 through the first through hole 14, and the second inlet 13 is connected to one end of the second delivery channel 113 through the second through hole 15. In another embodiment, one end of the first delivery channel 111 extends transversely to the side of the first carrier 1 to form the second inlet 13, and the first delivery channel 113a of the second delivery channel 113 extends transversely to the side of the first carrier 1 to form the first inlet 12. In other embodiments, the second inlet 13 can be located on a side surface of the first carrier 1 away from the second carrier 2, and the first inlet 12 is located on the side of the first carrier 1, or the second inlet 13 is located on the side of the first carrier 1, and the first inlet 12 is located on a side surface of the first carrier 1 away from the second carrier 2. The setting positions of the first inlet 12 and the second inlet 13 can be selected as needed.

[0051] In one embodiment, the outlet 21 is located on a side surface of the first carrier 1 facing away from the second carrier 2. At this time, the first carrier 1 has a third through hole penetrating the first carrier 1, and the outlet 21 is connected to an end of the second delivery channel 113 facing away from the first inlet 12 through the third through hole. At this time, the first carrier 1 and the second carrier 2 can be directly bonded, and there is no need to align the first carrier 1 and the second carrier 2, which effectively reduces the manufacturing difficulty of the microfluidic chip, effectively improves the yield of the microfluidic chip, and effectively reduces the manufacturing cost.

[0052] In another embodiment, see Figure 2 , the outlet 21 is located on the side surface of the second carrier plate 2 away from the first carrier plate 1. At this time, see Figure 5 The second carrier plate 2 has a fourth through hole 22 that penetrates the second carrier plate 2, and the outlet 21 is connected to the end of the second transmission channel 113c away from the second inlet 13 through the fourth through hole; when the first carrier plate 1 and the second carrier plate 2 are bonded, the fourth through hole needs to be aligned with the end of the second transmission channel 113c away from the second inlet 13, and because it has a larger size than the fourth through hole, the alignment accuracy requirement is relatively low, as long as the orthographic projection of the end of the second transmission channel 113c away from the second inlet 13 on the second carrier plate 2 is located in the fourth through hole, so the manufacturing difficulty of the microfluidic chip is also relatively low. Optional, see Figure 2 A receiving groove 16 is also provided on one side surface of the first carrier plate 1 provided with the microchannel 112. The receiving groove 16 is located at one end of the second transmission channel 113c away from the second inlet 13 and is connected to the second transmission channel 113c. The depth of the receiving groove 16 can be the same as the depth of the second transmission channel 113c. The area of ​​the fourth through hole is greater than or equal to the area of ​​the receiving groove 16. When the first carrier plate 1 and the second carrier plate 2 are adhered to each other, it is only necessary that the orthographic projection of the receiving groove 16 on the second carrier plate 2 is located in the fourth through hole or coincides with the fourth through hole. The alignment accuracy is low, which effectively reduces the manufacturing cost.

[0053] In other embodiments, the end of the second transmission channel 113c away from the first inlet 12 extends laterally to the side of the first carrier to form an outlet. In this case, the first carrier 1 and the second carrier 2 can be directly bonded, without involving the alignment step of the first carrier 1 and the second carrier 2, which effectively reduces the manufacturing difficulty of the microfluidic chip, effectively improves the yield of the microfluidic chip, and effectively reduces the manufacturing cost. The location of the outlet can be selected as needed.

[0054] It should be noted that the "side surface of the first carrier" mentioned in the present application refers to the surface perpendicular to the extension direction of the first carrier; the first delivery channel, the microchannel and the second delivery channel are all grooves with smaller width and depth, and the depth mentioned in the present application refers to the depth of the groove, and the width of the groove refers to the average distance between the surfaces on both sides of the groove.

[0055] Below Figure 1-5 The process of generating droplets in the microfluidic chip shown is described as follows:

[0056] The first fluid enters the main transmission channel 111a of the first delivery channel from the first inlet 12, and then enters the distribution channel 111b and multiple microchannels 112 in sequence; the second fluid enters the first transmission channel 113a from the second inlet 13, and then enters the intersection channel 113b; at the intersection of the microchannel 112 and the intersection channel 113b, the first fluid is subjected to different gradient shear forces, thereby generating droplets, and the generated droplets are transmitted to the outside of the microfluidic chip through the second transmission channel 113c and the outlet 21 along with the flowing continuous phase liquid, and are collected in a storage container.

[0057] See also Figure 6 The embodiment of the present application also provides a PCR (Polymerase Chain Reaction) detection device, including: a microfluidic chip 501 as shown in the above embodiment, used to disperse the detection sample into multiple droplets; an amplification unit 502, used to amplify the amount of nucleic acid in the droplets; and a droplet reading unit 503, used to perform droplet reading analysis on the droplets to obtain the nucleic acid content of the detection sample.

[0058] The PCR detection device of the embodiment of the present application is provided with the microfluidic chip shown in the above embodiment. In the microfluidic chip, the first fluid passes through the first delivery channel and the microfluidic channel, and generates droplets at the intersection of the microfluidic channel and the second delivery channel, and the second delivery channel is configured to transport the second fluid of the continuous phase to transport the generated droplets to the outlet of the microfluidic chip. Therefore, after the droplets are generated, they will not accumulate inside the microfluidic chip, thereby avoiding the problems of droplet fusion, less effective droplets, and worse droplet particle size CV, and improving the droplet generation efficiency and droplet particle size uniformity.

[0059] It should be understood that the application of the microfluidic chip provided in this application to a PCR detection device is only one of the main application scenarios of the microfluidic chip. In other embodiments, the microfluidic chip provided in this application can also be applied to cell sorting and other drug preparation scenarios. Since the principle and process of generating droplets are the same, it also has the technical effects produced by the above embodiments, which are not limited here one by one.

[0060] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the embodiments. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. The obvious changes or modifications derived therefrom are still within the scope of protection of the present invention.

Claims

1. A microfluidic chip, characterized in that: The microfluidic chip is provided with a first inlet, a second inlet and an outlet; the microfluidic chip is also provided with a first delivery channel, a microchannel and a second delivery channel; the second delivery channel includes a first delivery channel, a junction channel and a second delivery channel which are connected in sequence; The first inlet is connected to the first delivery channel; the second inlet is connected to the first delivery channel, and the outlet is connected to the second delivery channel; there are multiple microchannels, and the inlet end of each microchannel is connected to the first The delivery channel is connected at one end away from the first inlet, and the outlet end of each microchannel is connected to the side wall of the intersection channel; the outlet ends of multiple microchannels are arranged in sequence on one side wall of the intersection channel.

2. The microfluidic chip according to claim 1, characterized in that: The depth of the micro channel is smaller than the depth of the intersection channel.

3. The microfluidic chip according to claim 2, characterized in that: The microchannel and the intersection channel have a set depth difference, and the set depth difference is 15 μm to 1000 μm; or, the set depth difference is greater than the diameter of the droplets generated at the intersection.

4. The microfluidic chip according to claim 1, characterized in that: The depth of the micro channel is less than the depth of the first delivery channel; and / or the depth of the first delivery channel is the same as the depth of the intersection channel.

5. The microfluidic chip according to claim 1, characterized in that: The first delivery channel includes a main transmission channel and a distribution channel connected in sequence, the main transmission channel is connected to the first inlet, and the end of the main transmission channel away from the first inlet is connected to the distribution channel; the inlet end of each microchannel is respectively connected to a side wall of the distribution channel; the inlet ends of the microchannels are arranged in sequence along the side wall of the distribution channel.

6. The microfluidic chip according to claim 1 or 5, characterized in that: The intersection angle between the microchannel and the side wall of the intersection channel is 80-100°, and / or the intersection angle between the microchannel and the side wall of the distribution channel is 80-100°.

7. The microfluidic chip according to claim 1, characterized in that: The microfluidic chip includes a first carrier plate and a second carrier plate, and the first carrier plate and the second carrier plate are fixedly connected; wherein the first transport channel, the microchannel and the second transport channel are all arranged on a side surface of the first carrier plate facing the second carrier plate.

8. The microfluidic chip according to claim 7, characterized in that: The first inlet and the second inlet are both located on a side surface of the first carrier plate facing away from the second carrier plate, and / or the outlet is located on a side surface of the second carrier plate facing away from the first carrier plate.

9. The microfluidic chip according to claim 7, characterized in that: The second delivery channel extends to a side surface of the first carrier plate to form the outlet.

10. The microfluidic chip according to claim 8, characterized in that: The second carrier plate has a fourth through hole penetrating the second carrier plate, the outlet is located on a side surface of the second carrier plate facing away from the first carrier plate, and the fourth through hole connects the second delivery channel and the outlet.

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