Microfluidic Chip
By designing Tesla valve pipelines and corresponding cavity structures in the microfluidic chip, the problem of difficulty in stably opening and closing of microfluidic valves is solved, and precise control of reagent flow and the complexity of chemical reactions are achieved.
Patent Information
- Application Number
- CN202211006592.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-08-22
- Publication Date
- 2025-03-14
- Estimated Expiration
- 2042-08-22
AI Technical Summary
Microfluidic valves in related technologies are difficult to open and close stably, affecting the control of the liquid circuit.
A microfluidic chip is designed, including a Tesla valve pipeline and a corresponding liquid inlet and reaction chamber. By setting the one end of the Tesla valve pipeline close to the rotation center shaft, the one end away from the rotation center shaft has a liquid outlet, and is configured to form a preset resistance, so that the microfluidic valve can achieve stable opening and closing by changing the speed of the chip about the rotation center shaft.
The stable opening and closing of microfluidic valves is realized, and the reagent addition sequence and reaction steps can be accurately controlled, which improves the complexity and stability of chemical reactions in microfluidic chips.
Smart Images

Figure CN115518698B_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of microfluidics technology, and in particular to a microfluidics chip. Background Art
[0002] Microfluidic chip is a hot area in the development of miniaturized total analysis systems. It refers to a series of experiments involved in various biological, chemical, medical and other fields, including sample pretreatment, sample reaction and result reading, integrated into a chip with micro-nano size structure. Among them, centrifugal microfluidic chip refers to a type of chip that uses centrifugal force as a power to drive samples or reagents to move in the microchannels of the chip for detection. In order to control the on-off of the liquid path on the centrifugal microfluidic chip, a microfluidic valve is provided in the related technology. Through the special structural design on the microfluidic chip, such as capillaries, surface modification, thin films and other structures, the flow of fluid is inhibited, thereby controlling the opening and closing of the microfluidic valve to achieve the on-off of the liquid path.
[0003] However, the microfluidic valve in the related art has the problem of being difficult to open and close stably. Summary of the invention
[0004] Based on this, it is necessary to provide a microfluidic chip that enables microfluidic valves to open and close stably in order to address the problem that microfluidic valves in related technologies are difficult to open and close stably.
[0005] According to one aspect of the present application, a microfluidic chip is provided, comprising:
[0006] A chip body having a central axis of rotation;
[0007] at least one microfluidic valve, the microfluidic valve comprising a Tesla valve circuit, the Tesla valve circuit having a liquid inlet and a liquid outlet at opposite ends thereof, the distance between the liquid inlet and the rotation center axis is smaller than the distance between the liquid outlet and the rotation center axis, and the Tesla valve circuit is configured to form a preset resistance to a fluid flowing from the liquid inlet to the liquid outlet; and
[0008] The liquid inlet chamber and the reaction chamber correspond to the microfluidic valve one by one respectively, the liquid inlet chamber is connected with the liquid inlet of the Tesla valve pipeline of the corresponding microfluidic valve, and the reaction chamber is connected with the liquid outlet of the Tesla valve pipeline of the corresponding microfluidic valve.
[0009] The above-mentioned microfluidic chip, by setting a microfluidic valve including a Tesla valve pipeline, the Tesla valve pipeline has a liquid inlet at one end close to the rotation center axis, and the Tesla valve pipeline has a liquid outlet at one end away from the rotation center axis, so that when the chip body rotates around the rotation center axis, the flow direction of the fluid under the action of centrifugal force is from the liquid inlet to the liquid outlet. Since the Tesla valve pipeline is configured to form a preset resistance to the fluid flowing from the liquid inlet to the liquid outlet, the microfluidic chip needs to rotate around the rotation center axis at a higher speed, so that the centrifugal force exerted on the fluid is greater than the preset resistance, so that the fluid at the liquid inlet can overcome the preset resistance and flow to the liquid outlet, that is, the microfluidic valve is opened. When the centrifugal force exerted on the fluid is less than the preset resistance, the fluid cannot flow from the liquid inlet to the liquid outlet, and the microfluidic valve is closed. Therefore, the size of the centrifugal force can be changed by changing the speed of the chip body rotating around the rotation center axis, so as to achieve stable opening and closing of the microfluidic valve.
[0010] In one embodiment, the Tesla valve pipeline includes a plurality of Tesla valve unit groups arranged along its extension direction and connected to each other, and the Tesla valve unit group includes at least one Tesla valve unit;
[0011] Each of the Tesla valve units has a reverse inlet end and a reverse outlet end at both ends along the direction from the liquid inlet to the liquid outlet, and each of the Tesla valve units is configured to block the fluid from flowing from the reverse inlet end to the reverse outlet end, so that the Tesla valve pipeline is configured to form a preset resistance to the fluid flowing from the liquid inlet to the liquid outlet.
[0012] In one embodiment, the Tesla valve unit includes a first channel and a second channel located on one side of the first channel, and the outlet of the first channel and the outlet of the second channel extend toward a side close to each other and merge to form a confluent channel.
[0013] In one embodiment, each of the Tesla valve unit groups includes at least two Tesla valve units arranged along a first direction, and two adjacent Tesla valve units in the same Tesla valve unit group are connected to each other;
[0014] The first direction is arranged to intersect with an extension direction of the Tesla valve pipeline.
[0015] In one embodiment, the Tesla valve pipeline includes a plurality of Tesla valve units arranged along its extension direction and connected to each other;
[0016] Each of the Tesla valve units comprises two pipes arranged opposite to each other and staggered in a direction from the liquid inlet to the liquid outlet, and the two pipes each have a first end and a second end in a direction from the liquid inlet to the liquid outlet;
[0017] The two pipelines include a first pipeline and a second pipeline, the second end of the first pipeline of the Nth Tesla valve unit extends toward the second pipeline of the Nth Tesla valve unit and is connected to the first pipeline of the N+1th Tesla valve unit; the first end of the second pipeline of the Nth Tesla valve unit is connected to a portion of the first pipeline of the Nth Tesla valve unit located between the first end and the second end, the second end of the second pipeline of the Nth Tesla valve unit extends toward the first pipeline of the N+1th Tesla valve unit and is connected to a portion of the second pipeline of the N+1th Tesla valve unit located between the first end and the second end; the first end of the first pipeline of the N+1th Tesla valve unit is connected to the second pipeline of the Nth Tesla valve unit.
[0018] In one embodiment, the second end of the first conduit of the Nth Tesla valve unit is located between the first end of the first conduit of the N+1th Tesla valve unit and the first end of the second conduit of the N+1th Tesla valve unit;
[0019] The second end of the second conduit of the Nth Tesla valve unit is located between the first end of the second conduit of the N+1th Tesla valve unit and the first end of the first conduit of the N+2th Tesla valve unit.
[0020] In one embodiment, the pipeline includes a liquid inlet section and a liquid outlet section which are connected to each other, the first end of the pipeline is arranged at an end of the liquid inlet section away from the liquid outlet section, and the second end of the pipeline is arranged at an end of the liquid outlet section away from the liquid inlet section, the liquid inlet section is constructed to be straight, and the liquid outlet section is constructed to be arc-shaped.
[0021] In one embodiment, the microfluidic valve extends along the radial direction of the chip body.
[0022] In one embodiment, the number of the microfluidic valves is multiple;
[0023] The plurality of microfluidic valves are arranged around the central axis of rotation and spaced apart from each other.
[0024] In one embodiment, the microfluidic valve includes a capillary valve or a hydrophobic valve. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Figure 1 This is a schematic diagram of the structure of a microfluidic chip in one embodiment of the present application;
[0026] Figure 2 for Figure 1A schematic diagram of the structure of the microfluidic valve, the liquid inlet chamber and the reaction chamber in the illustrated embodiment;
[0027] Figure 3 for Figure 2 A schematic diagram of the structure of a Tesla valve unit in the embodiment shown;
[0028] Figure 4 for Figure 2 A schematic diagram of the structures of the Nth to N+2nd Tesla valve units in the illustrated embodiment;
[0029] Figure 5 This is a schematic diagram of the structure of a microfluidic valve in another embodiment of the present application;
[0030] Figure 6 for Figure 5 A schematic diagram of the structure of a Tesla valve unit in the embodiment shown;
[0031] Figure 7 This is a schematic diagram of the structure of a microfluidic valve in another embodiment of the present application;
[0032] Figure 8 This is a schematic diagram of the structure of a microfluidic valve in yet another embodiment of the present application.
[0033] Description of reference numerals:
[0034] 1. Chip body; 2. Microfluidic valve; 20. Tesla valve pipeline; 21. Liquid inlet; 22. Liquid outlet; 23. Tesla valve unit group; 24. Tesla valve unit; 231. Reverse inlet end; 232. Reverse outlet end; 233. First channel; 234. Second channel; 235. Converging channel; 240. Pipeline; 241. First pipeline; 242. Second pipeline; 2401. First end; 2402. Second end; 2403. Liquid inlet section; 2404. Liquid outlet section; 30. Liquid inlet chamber; 40. Reaction chamber; 50. Distribution pipeline; 60. Sample loading chamber; 70. Siphon valve; 80. Waste liquid channel; A. First direction. DETAILED DESCRIPTION
[0035] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.
[0036] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.
[0037] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of this application, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.
[0038] In this application, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.
[0039] In the present application, unless otherwise clearly specified and limited, a first feature being “above” or “below” a second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, a first feature being “above”, “above”, and “above” a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being “below”, “below”, and “below” a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.
[0040] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used herein are for illustrative purposes only and are not intended to be the only implementation method.
[0041] Figure 1 This is a schematic diagram of the structure of a microfluidic chip in one embodiment of the present application; Figure 2 for Figure 1 Schematic diagram of the structure of the microfluidic valve, liquid inlet chamber and reaction chamber in the embodiment shown.
[0042] See also Figure 1-2 The microfluidic chip provided in one embodiment of the present application includes a chip body 1, at least one microfluidic valve 2, and a liquid inlet chamber 30 and a reaction chamber 40 corresponding to the microfluidic valve 2 respectively.
[0043] The chip body 1 has a central axis of rotation, and the microfluidic valve 2 includes a Tesla valve pipeline 20, and the opposite ends of the Tesla valve pipeline 20 respectively have a liquid inlet 21 and a liquid outlet 22, and the distance between the liquid inlet 21 and the central axis of rotation is smaller than the distance between the liquid outlet 22 and the central axis of rotation, and the Tesla valve pipeline 20 is configured to form a preset resistance to the fluid flowing from the liquid inlet 21 to the liquid outlet 22. The liquid inlet cavity 30 is connected to the liquid inlet 21 of the Tesla valve pipeline 20 of the corresponding microfluidic valve 2, and the reaction cavity 40 is connected to the liquid outlet 22 of the Tesla valve pipeline 20 of the corresponding microfluidic valve 2.
[0044] The above-mentioned microfluidic chip, by setting the microfluidic valve 2, includes a Tesla valve pipeline 20, and the Tesla valve pipeline 20 has a liquid inlet 21 at one end close to the rotation center axis, and a liquid outlet 22 at one end away from the rotation center axis, so that when the chip body 1 rotates around the rotation center axis, the flow direction of the fluid under the action of centrifugal force is from the liquid inlet 21 to the liquid outlet 22. Since the Tesla valve pipeline 20 is configured to form a preset resistance to the fluid flowing from the liquid inlet 21 to the liquid outlet 22, the chip body 1 needs to rotate around the rotation center axis at a higher speed, so that the centrifugal force on the fluid is greater than the preset resistance, so that the fluid at the liquid inlet 21 can overcome the preset resistance and flow to the liquid outlet 22, that is, the microfluidic valve 2 is opened. When the centrifugal force on the fluid is less than the preset resistance, the fluid cannot flow from the liquid inlet 21 to the liquid outlet 22, and the microfluidic valve 2 is closed. Therefore, the microfluidic valve 2 can be opened or closed by changing the rotation speed of the chip body 1 around the rotation center axis and the magnitude of the centrifugal force, and the microfluidic valve 2 can be stably maintained in an open state or a closed state within a certain rotation speed range.
[0045] In actual use, the reagent is first added to the liquid inlet chamber 30, and then the opening or closing of the microfluidic valve 2 is controlled by controlling the rotation speed of the chip body 1 around the central axis of rotation, that is, whether the reagent can enter the reaction chamber 40. Therefore, the microfluidic chip in the above embodiment can more accurately control the order of adding reagents and the reaction steps on the chip body 1, control the incubation time, and thus realize a complex multi-step chemical reaction.
[0046] The Tesla valve pipeline 20 based on different structures provides the following embodiments:
[0047] Embodiment 1:
[0048] Figure 3 for Figure 2 A schematic diagram of the structure of a Tesla valve unit in the embodiment shown; Figure 4 for Figure 2 A schematic diagram of the structures of the Nth to N+2nd Tesla valve units in the illustrated embodiment.
[0049] In some embodiments, in combination Figure 2-3 As shown, the Tesla valve pipeline 20 includes a plurality of Tesla valve units 24 arranged along its extension direction and connected to each other. Each Tesla valve unit 24 includes two pipes 240 arranged opposite to each other and staggered along the direction from the liquid inlet 21 to the liquid outlet 22. Both pipes 240 have a first end 2401 and a second end 2402 along the direction from the liquid inlet 21 to the liquid outlet 22. Figure 4As shown, the two pipes 240 include a first pipe 241 and a second pipe 242. The second end 2412 of the first pipe 241 of the Nth Tesla valve unit 24 extends toward the second pipe 242 of the Nth Tesla valve unit 24 and is connected to the first pipe 241 of the N+1th Tesla valve unit 24. The first end 2421 of the second pipe 242 of the Nth Tesla valve unit 24 is connected to a portion of the first pipe 241 of the Nth Tesla valve unit 24 between the first end 2411 and the second end 2412. The second end 2422 of the second pipe 242 of the Nth Tesla valve unit 24 extends toward the first pipe 241 of the N+1th Tesla valve unit 24 and is connected to a portion of the second pipe 242 of the N+1th Tesla valve unit 24 between the first end 2421 and the second end 2422. The first end 2411 of the first pipe 241 of the N+1th Tesla valve unit 24 is connected to the second pipe 242 of the Nth Tesla valve unit 24.
[0050] Thus, in the above embodiment, each Tesla valve unit 24 includes two pipes 240, and both pipes 240 have a first end 2401 and a second end 2402 along the direction of the liquid inlet 21 to the liquid outlet 22 (see Figure 3), so that when the chip body 1 rotates around the central axis of rotation, the flow direction of the fluid is from the first end 2401 of each pipeline 240 to the second end 2402 of the same pipeline 240. By setting the second end 2412 of the first pipeline 241 of the Nth Tesla valve unit 24 to extend toward the second pipeline 242 of the Nth Tesla valve unit 24, when the fluid flows from the liquid inlet 21 to the liquid outlet 22, the flow rate of the fluid flowing into the second end 2412 of the first pipeline 241 of the Nth Tesla valve unit 24 is different from the flow rate of the fluid flowing into the second pipeline 242 of the Nth Tesla valve unit 24. And because the first end 2411 of the first pipe 241 of the N+1th Tesla valve unit 24 is connected to the second pipe 242 of the Nth Tesla valve unit 24, when the fluid flows from the liquid inlet 21 to the liquid outlet 22, a part of the fluid entering the second pipe 242 of the Nth Tesla valve unit 24 flows out from the second end 2422 of the same second pipe 242, and the other part enters the first end 2411 of the first pipe 241 of the N+1th Tesla valve unit 24. Furthermore, since the second end 2412 of the first pipe 241 of the Nth Tesla valve unit 24 is connected to the first pipe 241 of the N+1th Tesla valve unit 24, the flow rate of the fluid that meets the connection point between the second end 2412 of the first pipe 241 of the Nth Tesla valve unit 24 and the first pipe 241 of the N+1th Tesla valve unit 24 is reversed, so that when the fluid flowing out of the second end 2412 of the first pipe 241 of the Nth Tesla valve unit 24 meets the fluid in the first pipe 241 of the N+1th Tesla valve unit 24, the fluid in the first pipe 241 of the N+1th Tesla valve unit 24 is blocked from flowing. Similarly, when the fluid flowing out of the second end 2422 of the second pipe 242 of the Nth Tesla valve unit 24 meets the fluid in the second pipe 242 of the N+1th Tesla valve unit 24, the fluid in the second pipe 242 of the N+1th Tesla valve unit 24 is blocked from flowing. Therefore, by setting the Tesla valve pipeline 20 to include multiple Tesla valve units 24 arranged along its extension direction and connected to each other, when the fluid flows from the Nth Tesla valve unit 24 into the N+1th Tesla valve unit 24, the connection between the Nth Tesla valve unit 24 and the N+1th Tesla valve unit 24 forms resistance to the fluid, so that the Tesla valve pipeline 20 forms a preset resistance to the fluid flowing from the liquid inlet 21 to the liquid outlet 22.
[0051] Specifically, N is a positive integer.
[0052] It should be noted that the flow velocities of the two fluids are in the same direction, which means that the two fluids move in the same direction, and the flow velocities of the two fluids are in opposite directions, which means that the two fluids move in opposite directions.
[0053] Specifically, Figure 4As shown, the second end 2412 of the first conduit 241 of the Nth Tesla valve unit 24 is located between the first end 2411 of the first conduit 241 of the N+1th Tesla valve unit 24 and the first end 2421 of the second conduit 242 of the N+1th Tesla valve unit 24. The second end 2422 of the second conduit 242 of the Nth Tesla valve unit 24 is located between the first end 2421 of the second conduit 242 of the N+1th Tesla valve unit 24 and the first end 2411 of the first conduit 241 of the N+2th Tesla valve unit 24. In this way, by arranging the second end 2412 of the first conduit 241 of the Nth Tesla valve unit 24 between the first end 2411 of the first conduit 241 of the N+1th Tesla valve unit 24 and the first end 2421 of the second conduit 242 of the N+1th Tesla valve unit 24, when the fluid flows into the first end 2411 of the first conduit 241 of the N+1th Tesla valve unit 24, it is blocked by the fluid flowing out of the second end 2412 of the first conduit 241 of the N+1th Tesla valve unit 24. That is, before the fluid in the first conduit 241 of the N+1th Tesla valve unit 24 is diverted into the second conduit 242 of the N+1th Tesla valve unit 24, the flow rate of the fluid in the first conduit 241 of the N+1th Tesla valve unit 24 is reduced, thereby reducing the flow rate of the fluid diverted into the second conduit 242 of the N+1th Tesla valve unit 24, and further increasing the preset resistance formed by the Tesla valve pipeline 20 to the fluid flowing from the liquid inlet 21 to the liquid outlet 22.
[0054] It can be understood that when the preset resistance formed by the Tesla valve pipeline 20 to the fluid flowing from the liquid inlet 21 to the liquid outlet 22 is increased, a larger centrifugal force is required to make the fluid flow from the liquid inlet 21 to the liquid outlet 22. Therefore, when the rotation speed of the chip body 1 around the rotation center axis is greater than the critical speed corresponding to the preset resistance, the microfluidic valve 2 is opened, and when the rotation speed of the chip body 1 around the rotation center axis is greater than the critical speed corresponding to the preset resistance, the microfluidic valve 2 is opened. It can be seen that in the above embodiment, by increasing the preset resistance formed by the Tesla valve pipeline 20 to the fluid flowing from the liquid inlet 21 to the liquid outlet 22, the stability and reliability of the closing of the microfluidic valve 2 when the chip body 1 works under high speed conditions are improved.
[0055] The critical speed is the speed value at which the chip body 1 rotates around the central axis of rotation when the microfluidic valve 2 is opened.
[0056] In some embodiments, such as Figure 2-4As shown, the pipeline 240 includes a liquid inlet section 2403 and a liquid outlet section 2404 that are connected to each other, the first end 2401 of the pipeline 240 is arranged at one end of the liquid inlet section 2403 away from the liquid outlet section 2404, the second end 2402 of the pipeline 240 is arranged at one end of the liquid outlet section 2404 away from the liquid inlet section 2403, the liquid inlet section 2403 is configured to be straight, and the liquid outlet section 2404 is configured to be arc-shaped. In this way, by setting the liquid outlet section 2404 to be arc-shaped, the extension direction of the liquid outlet section 2404 of the same pipeline 240 is different from the extension direction of the liquid inlet section 2403, so that the second end 2412 of the first pipeline 241 can extend toward the second pipeline 242 of the same Tesla valve unit 24.
[0057] Embodiment 2:
[0058] Figure 5 This is a schematic diagram of the structure of a microfluidic valve in another embodiment of the present application; Figure 6 for Figure 5 A schematic diagram of the structure of a Tesla valve unit in the embodiment shown; Figure 7 This is a schematic diagram of the structure of a microfluidic valve in another embodiment of the present application.
[0059] In some embodiments, such as Figure 5-6 As shown, the Tesla valve pipeline 20 includes a plurality of Tesla valve unit groups 23 arranged along its extension direction and connected to each other, and the Tesla valve unit group 23 includes at least one Tesla valve unit 24. Each Tesla valve unit 24 has a reverse inlet end 231 and a reverse outlet end 232 at both ends along the direction from the liquid inlet 21 to the liquid outlet 22, respectively. Each Tesla valve unit 24 is configured to be able to block the fluid from the reverse inlet end 231 to the reverse outlet end 232, so that the Tesla valve pipeline 20 is configured to be able to form a preset resistance to the fluid flowing from the liquid inlet 21 to the liquid outlet 22. In this way, when the fluid flows from the liquid inlet 21 to the liquid outlet 22, the fluid flows through the plurality of Tesla valve unit groups 23, and when the fluid flows through each Tesla valve unit group 23, the fluid flows from the reverse inlet end 231 of the Tesla valve unit 24 of the Tesla valve unit group 23 to the reverse outlet end 232, so that the fluid is blocked by the Tesla valve unit 24, so that the flow rate of the fluid is reduced. Since the fluid needs to pass through multiple groups of Tesla valve units 23 before flowing to the liquid outlet 22 after flowing into the Tesla valve pipeline 20 from the liquid inlet 21, the Tesla valve pipeline 20 forms a larger preset resistance to the fluid, so that when the chip body 1 works under high speed conditions, the microfluidic valve 2 can be stably and reliably closed.
[0060] In addition, in the above embodiment, the Tesla valve pipeline 20 includes a plurality of Tesla valve unit groups 23 arranged along the extension direction thereof and connected to each other, so that after the fluid passes through the Tesla valve pipeline 20 for the first time, the fluid remaining in the Tesla valve pipeline 20 is deposited to a section of the Tesla valve pipeline 20 near the liquid outlet 22 under the action of centrifugal force. At this time, the section of the Tesla valve pipeline 20 near the liquid inlet 21 remains unobstructed, so no occluded droplets are formed in the Tesla valve pipeline 20, so that the gas at both ends of the microfluidic valve 2 moves freely, and the air pressure at both ends of the microfluidic valve 2 is balanced. In this way, when the fluid needs to pass through the microfluidic valve 2 for the second time, the centrifugal force for opening the microfluidic valve 2 is the same as the centrifugal force of the previous time, so that the centrifugal force for opening the microfluidic valve 2 multiple times is kept constant, thereby facilitating the repeated use of the microfluidic valve 2 and enabling multi-step chemical reactions. For example, in actual use, different types of reagents can be added to the liquid inlet chamber 30 in the order required by the experimental reaction, and after each addition of one or more reagents to the liquid inlet chamber 30, the microfluidic valve 2 is opened, so that different types of reagents can enter the reaction system in the order required by the experimental reaction, and the incubation time is controlled to accurately control the order of liquid flow and the reaction process, thereby increasing the complexity of chemical reactions in the microfluidic chip and expanding the categories of chemical reactions in the microfluidic chip.
[0061] Specifically, Figure 6 As shown, the Tesla valve unit 24 includes a first channel 233 and a second channel 234 located on one side of the first channel 233. The outlet of the first channel 233 and the outlet of the second channel 234 extend toward the side close to each other and intersect to form a converging channel 235. In this way, the flow rate of the fluid flowing out of the outlet of the first channel 233 is reversed to the flow rate of the fluid flowing out of the outlet of the second channel 234, thereby reducing the flow rate of the fluid flowing out of the outlet of the first channel 233 and the flow rate of the fluid flowing out of the outlet of the second channel 234, respectively. Therefore, when the fluid flows through each Tesla valve unit 24 in the direction from the reverse inlet end 231 to the reverse outlet end 232, it is blocked, so that the flow rate of the fluid is reduced.
[0062] Figure 8 This is a schematic diagram of the structure of a microfluidic valve in yet another embodiment of the present application.
[0063] In some embodiments, such as Figure 7-8As shown, each Tesla valve unit group 23 includes at least two Tesla valve units 24 arranged along a first direction, and two adjacent Tesla valve units 24 in the same Tesla valve unit group 23 are connected to each other. The first direction is arranged to intersect with the extension direction of the Tesla valve pipeline 20. In this way, by setting each Tesla valve unit group 23 to include at least two Tesla valve units 24 arranged along the first direction, the number of connection points of adjacent groups of Tesla valve units 24 in the Tesla valve pipeline 20 is increased, so that when the fluid flows through the Tesla valve pipeline 20 from the liquid inlet 21 to the liquid outlet 22, the number of bifurcations and confluences passed by the fluid increases. It should be noted that when the fluid flows in the flow channel, the sudden increase or decrease of the flow channel area at the front end thereof will generate resistance, so when the fluid passes through the bifurcations and confluences, a large liquid resistance is generated. Therefore, by arranging each Tesla valve unit group 23 to include at least two Tesla valve units 24 arranged along the first direction, the fluid passes through a plurality of staggered bifurcations and confluences, thereby further improving the preset resistance formed by the Tesla valve pipeline 20 to the fluid flowing from the liquid inlet 21 to the liquid outlet 22, and further improving the stability and reliability of the closing of the microfluidic valve 2 when the chip body 1 works under high speed conditions.
[0064] Specifically, Figure 7-8 As shown, two adjacent Tesla valve units 24 in the same Tesla valve unit group 23 are staggered along a first direction so that when the fluid flows from a Tesla valve unit 24 in one Tesla valve unit group 23 into a Tesla valve unit 24 in an adjacent Tesla valve unit group 23, the flow channel area at the front end of the fluid can suddenly increase or decrease.
[0065] Alternatively, if Figure 5 and Figure 7-8 As shown, the number of Tesla valve units 24 included in each Tesla valve unit group 23 can be 1 to 3. In other embodiments, the number of Tesla valve units 24 included in each Tesla valve unit group 23 can also be set according to the use requirements, as long as it can meet the requirements of the preset resistance size formed by the Tesla valve pipeline 20 to the fluid flowing from the liquid inlet 21 to the liquid outlet 22, and is not limited here.
[0066] In some embodiments, the microfluidic valve 2 includes a capillary valve.
[0067] In other embodiments, the microfluidic valve 2 includes a hydrophobic valve. It should be noted that when the microfluidic valve 2 adopts a hydrophobic valve, the surface of the microfluidic valve 2 is hydrophobically modified. Since the height of the flow channel in the microfluidic valve 2 directly affects the resistance of the microfluidic valve 2, when the critical speed for opening the microfluidic valve 2 needs to be set to be extremely high, the height of the corresponding flow channel is extremely low, resulting in increased processing difficulty. At this time, by performing hydrophobic modification, the height of the flow channel of the microfluidic valve 2 can be appropriately increased, reducing the processing difficulty.
[0068] based on Figure 7 Table 1 shows the critical speeds corresponding to different heights of Tesla valve lines 20 obtained by testing the microfluidic valve 2 at a given center distance position. The critical speed is the speed value at which the chip body 1 rotates around the central axis of rotation when the microfluidic valve 2 is opened. For ease of presentation, the given center distance is the distance between the central axis of rotation and the liquid inlet 21 of the Tesla valve line 20, which is 3 cm. The material of the chip body 1 is PMMA (polymethylmethacrylate), and the thickness of the chip body 1 is 1 mm, which does not mean that the microfluidic valve 2 can only be arranged in a space with a center distance of 3 cm, nor does it mean that the microfluidic valve 2 can only be used on PMMA, nor does it mean that the chip thickness can only be 1 mm.
[0069] Table 1
[0070] Tesla valve line 20 height Critical speed (rpm) 50 microns >3000 100 microns 1500 200 microns 600 400 microns 300 600 microns 200 1000 microns 100
[0071] based on Figure 7 Table 2 shows the critical speeds corresponding to different center distances obtained by testing the microfluidic valve 2 provided in the embodiment shown, given the height of the Tesla valve pipeline 20. For ease of presentation, the height of the Tesla valve pipeline 20 is 100 microns, the material of the chip body 1 is PMMA, and the thickness of the chip body 1 is 1 mm.
[0072] Table 2
[0073]
[0074]
[0075] based on Figure 7 Table 3 shows the stability of six microfluidic valves 2 provided in the microfluidic valve 2 of the embodiment shown in the figure, given the center distance and the height of the Tesla valve pipeline 20. For ease of presentation, the center distance is 3 cm, the height of the Tesla valve pipeline 20 is 100 μm, the material of the chip body 1 is PMMA, and the thickness of the chip body 1 is 1 mm.
[0076] Table 3
[0077] Speed (rpm) Stability of microfluidic valve 2 1000 All 6 valves are closed 2000 All 6 valves are open
[0078] It can be seen from Table 3 that the microfluidic valve 2 in the above embodiment has high stability, that is, it can remain stably closed or stably opened at different rotation speeds.
[0079] In some embodiments, such as Figure 1 As shown, there are multiple microfluidic valves 2, and the multiple microfluidic valves 2 are arranged at intervals around the rotation center axis. In this way, reagents as different samples can be respectively placed in the multiple liquid inlet cavities 30 corresponding to the multiple microfluidic valves 2, so that when the chip body 1 rotates around the rotation center axis, multiple samples can be detected.
[0080] Optionally, the plurality of microfluidic valves 2 are rotationally symmetric about the rotation center axis, so that when the chip body 1 rotates around the rotation center axis, the microfluidic valves 2 symmetrical to each other are opened or closed synchronously, so that the symmetrical units on the chip body 1 perform the same operation.
[0081] In some embodiments, such as Figure 1 As shown, the microfluidic valve 2 extends in the radial direction of the chip body 1 to better utilize the space on the chip body 1. In other embodiments, the extension direction of the microfluidic valve 2 can also be arranged to cross the radial direction of the chip body 1, as long as the distance between the liquid inlet 21 of the Tesla valve pipeline 20 and the rotation center axis is smaller than the distance between the liquid outlet 22 of the Tesla valve pipeline 20 and the rotation center axis, which is not limited here.
[0082] In some embodiments, such as Figure 1 As shown, there are multiple microfluidic valves 2, and the microfluidic chip also includes at least one distribution pipeline 50 respectively connected to multiple liquid inlet chambers 30, and sample loading chambers 60 connected to the distribution pipelines 50 one by one, and the distribution channel is located on the side of the corresponding sample loading chamber 60 away from the rotation center axis. In this way, by setting the sample loading chamber 60, reagents can be added and the reagents can enter the corresponding liquid inlet chamber 30 through the distribution pipeline 50.
[0083] Optionally, the volumes of the multiple liquid inlet chambers 30 connected to the same distribution channel are the same.
[0084] In some embodiments, such as Figure 1 As shown, the microfluidic chip further includes a siphon valve 70 connected to the reaction chamber 40 in a one-to-one correspondence, so that the fluid in the reaction chamber 40 can flow out of the reaction chamber 40 through the siphon valve 70 under the action of capillary force after the chip body 1 stops rotating.
[0085] Furthermore, if Figure 1As shown, the microfluidic chip also includes a waste liquid channel 80 corresponding to the distribution channel one by one, and the waste liquid channel 80 is connected to the corresponding reaction chamber 40 to receive the fluid flowing out of the reaction chamber 40 through the siphon valve 70 after the reaction is completed.
[0086] Based on the microfluidic chip provided in the above embodiment, a method for using the microfluidic chip is provided:
[0087] S110: Pre-place the magnetic beads and enzyme freeze-dried beads in the liquid inlet chamber 30, dilute and mix the sample plasma with the matching diluent, and then add them to the sample loading chamber 60, with the loading volume being 100-500ul;
[0088] S120: rotating the chip body 1 around the rotation center axis at a first preset rotation speed less than the critical rotation speed for a first preset rotation time;
[0089] In this way, the fluid in the sample loading chamber 60 passes through the distribution channel under the action of centrifugal force and fills the liquid inlet cavity 30. Optionally, the critical speed is 1200 rpm to 2000 rpm, the first preset speed is 500 rpm to 1000 rpm, and the first preset rotation time is 20s to 60s.
[0090] S130: rotating the chip body 1 around the rotation center axis at a second preset rotation speed greater than the critical rotation speed for a second preset rotation time;
[0091] In this way, the microfluidic valve 2 is opened, and the fluid in the liquid inlet chamber 30 flows into the corresponding reaction chamber 40 through the microfluidic valve 2 to start the reaction. Optionally, the second preset rotation speed is 1500 rpm.
[0092] S140: rotating the chip body 1 around the rotation center axis for a third preset rotation time, and the rotation speed of the chip body 1 changes alternately within the first preset rotation speed range.
[0093] In this way, the freeze-dried spheres are dissolved and mixed. Optionally, the first preset rotation speed range is 1000 rpm to 3000 rpm, and the third preset rotation time is 10 minutes to 15 minutes.
[0094] S150: Stop the chip body 1 from rotating, and the duration of the chip body 1 stopping rotating is a first preset stop time.
[0095] In this way, the fluid passes through the siphon valve 70 under the action of capillary force. Optionally, the first preset stop time is 10s to 30s.
[0096] S160 : rotating the chip body 1 around the central axis of rotation at a first preset rotation speed for 20 seconds, so that the fluid enters the waste liquid channel 80 .
[0097] Furthermore, the method for using the microfluidic chip also includes:
[0098] Add cleaning liquid to the sample loading chamber 60, with a sample volume of 100-500ul, and rotate the chip body 1 around the rotation center axis at the first preset speed for 20s to 60s, so that the cleaning liquid fills the liquid inlet chamber 30. Then rotate the chip body 1 around the rotation center axis at the second preset speed, so that the cleaning liquid enters the reaction chamber 40, and rotates clockwise alternately. The speed of the chip body 1 alternates within the first preset speed range, and the duration is 3 minutes. Stop for 10-30s to allow the cleaning liquid to pass through the siphon valve 70 under the action of capillary force. Rotate the chip body 1 around the rotation center axis at the first preset speed for 20s, so that the liquid reaches the waste liquid channel 80. Repeat 2-3 times.
[0099] Add the substrate to the sample loading chamber 60, with a loading volume of 100-500ul. The chip body 1 is rotated around the rotation center axis at a first preset speed for 20s to 60s, so that the substrate passes through the distribution pipe 50 and fills the liquid inlet chamber 30. The chip body 1 is then rotated around the rotation center axis at a second preset speed, so that the substrate enters the reaction chamber 40, where it is alternately accelerated clockwise, with the speed maintained at 1000-3000rpm within 1 minute, and the duration is 3 minutes. Detection is performed after stopping for 5 minutes.
[0100] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0101] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.
Claims
1. A microfluidic chip, characterized in that: include: A chip body having a central axis of rotation; at least one microfluidic valve, the microfluidic valve comprising a Tesla valve circuit, the Tesla valve circuit having a liquid inlet and a liquid outlet at opposite ends thereof, the distance between the liquid inlet and the rotation center axis is smaller than the distance between the liquid outlet and the rotation center axis, and the Tesla valve circuit is configured to form a preset resistance to a fluid flowing from the liquid inlet to the liquid outlet; and A liquid inlet chamber and a reaction chamber respectively corresponding to the microfluidic valve, the liquid inlet chamber being communicated with the liquid inlet of the Tesla valve pipeline of the corresponding microfluidic valve, and the reaction chamber being communicated with the liquid outlet of the Tesla valve pipeline of the corresponding microfluidic valve; The Tesla valve pipeline includes a plurality of Tesla valve units arranged along its extension direction and connected to each other; Each of the Tesla valve units comprises two pipes arranged opposite to each other and staggered in a direction from the liquid inlet to the liquid outlet, and the two pipes each have a first end and a second end in a direction from the liquid inlet to the liquid outlet; The two pipelines include a first pipeline and a second pipeline, the second end of the first pipeline of the Nth Tesla valve unit extends toward the second pipeline of the Nth Tesla valve unit and is connected to the first pipeline of the N+1th Tesla valve unit; the first end of the second pipeline of the Nth Tesla valve unit is connected to a portion between the first end and the second end of the first pipeline of the Nth Tesla valve unit, the second end of the second pipeline of the Nth Tesla valve unit extends toward the first pipeline of the N+1th Tesla valve unit and is connected to a portion between the first end and the second end of the second pipeline of the N+1th Tesla valve unit; the first end of the first pipeline of the N+1th Tesla valve unit is connected to the second pipeline of the Nth Tesla valve unit; The second end of the first pipeline of the Nth Tesla valve unit is located between the first end of the first pipeline of the N+1th Tesla valve unit and the first end of the second pipeline of the N+1th Tesla valve unit; The second end of the second conduit of the Nth Tesla valve unit is located between the first end of the second conduit of the N+1th Tesla valve unit and the first end of the first conduit of the N+2th Tesla valve unit; The pipeline includes a liquid inlet section and a liquid outlet section which are connected to each other, the first end of the pipeline is arranged at an end of the liquid inlet section away from the liquid outlet section, and the second end of the pipeline is arranged at an end of the liquid outlet section away from the liquid inlet section, the liquid inlet section is constructed to be straight, and the liquid outlet section is constructed to be arc-shaped.
2. The microfluidic chip according to claim 1, characterized in that: The Tesla valve pipeline includes a plurality of Tesla valve unit groups arranged along its extension direction and connected to each other, and the Tesla valve unit group includes at least one Tesla valve unit; Each of the Tesla valve units has a reverse inlet end and a reverse outlet end at both ends along the direction from the liquid inlet to the liquid outlet, and each of the Tesla valve units is configured to block the fluid from flowing from the reverse inlet end to the reverse outlet end, so that the Tesla valve pipeline is configured to form a preset resistance to the fluid flowing from the liquid inlet to the liquid outlet.
3. The microfluidic chip according to claim 2, characterized in that: The Tesla valve unit includes a first channel and a second channel located on one side of the first channel. The outlet of the first channel and the outlet of the second channel extend toward a side close to each other and meet to form a merged channel.
4. The microfluidic chip according to claim 3, characterized in that: Each of the Tesla valve unit groups includes at least two Tesla valve units arranged along a first direction, and two adjacent Tesla valve units in the same Tesla valve unit group are connected to each other; The first direction is arranged to intersect with an extension direction of the Tesla valve pipeline.
5. The microfluidic chip according to claim 1, characterized in that: The microfluidic chip also includes siphon valves connected to the reaction chambers in a one-to-one correspondence.
6. The microfluidic chip according to claim 5, characterized in that: There are multiple microfluidic control valves, and the microfluidic chip also includes at least one distribution pipe connected to the multiple liquid inlet chambers respectively, and sample loading chambers connected to the distribution pipes one by one, and the distribution channel is located on the side of the corresponding sample loading chamber away from the rotation center axis.
7. The microfluidic chip according to claim 5, characterized in that: The volumes of the plurality of liquid inlet chambers connected to the same distribution pipe are the same.
8. The microfluidic chip according to claim 1, characterized in that: The microfluidic valve extends along the radial direction of the chip body.
9. The microfluidic chip according to claim 1, characterized in that: The number of the microfluidic valves is multiple; The plurality of microfluidic valves are arranged around the central axis of rotation and spaced apart from each other.
10. The microfluidic chip according to claim 1, characterized in that: The microfluidic valve includes a capillary valve or a hydrophobic valve.
Citation Information
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