A centrifugal microfluidic chip and its preparation method

Abstract

The present invention provides a centrifugal microfluidic chip and a preparation method thereof, belonging to the technical field of microfluidics, including a chip body; a first reaction chamber, the first reaction chamber is located on the chip body and close to the rotation center of the chip body; a second reaction chamber, the second reaction chamber is located on the chip body and is farther from the rotation center than the first reaction chamber; a fluid switching valve, the fluid switching valve is connected to the first reaction chamber and the second reaction chamber, and the fluid switching valve can repeatedly close or communicate the first reaction chamber and the second reaction chamber under the conditions of the rotation and heating of the chip body. The present invention can conveniently realize the controllable batch release and precise quantitative release of the upstream liquid, and has a simple structure, which is convenient for reducing the production and manufacturing cost and the complexity of fluid controlled release.

Description

Technical Field

[0001] This application relates to the field of microfluidic technology, and particularly relates to a centrifugal microfluidic chip and a preparation method thereof. Background Art

[0002] In order to meet the detection requirements, a microfluidic chip kit needs to perform various operations such as processing, mixing, separating, and releasing liquid components such as samples and reagents. Various microvalves inside the chip kit (such as mechanical valves, pneumatic valves, solenoid valves, capillary valves, and phase change valves, etc.) are key components used to guide the liquid flow or determine the liquid movement pattern. The paraffin valve, as one of the most typical and commonly used phase change valves, controls the melting and solidification of paraffin by heating and cooling, and then realizes the opening and closing of the valve. Its characteristics are simple structure and convenient opening and closing. Generally, no additional complex component modules are required except for the heating module required for the detection itself, and it hardly affects the activity of various biochemical reagents and detection reactions (such as PCR, LAMP, and RPA, etc.). It is an ideal microfluidic valve.

[0003] However, there are still some problems in the application of paraffin valves in the current microfluidic chip field. The most prominent one is that most paraffin valves are for single use only and cannot achieve a controllable multiple-switching function, and cannot meet the controllable batch-by-batch release and precise quantitative release of upstream liquids. This has greatly restricted the further application of paraffin valves in the microfluidic field. In addition, the overly complex structural design of paraffin valve components also leads to an increase in the cost during the manufacturing or use of microfluidic products, and even affects the stability and reliability of microfluidic products themselves.

[0004] The Chinese invention patent with publication number CN114561283A discloses a fully automatic nucleic acid extraction and constant temperature amplification detection integrated machine, in which the paraffin valve designed at the liquid outlet is composed of a heat-conducting metal ring filled with paraffin, and the outer wall of the heat-conducting metal ring contacts the heat-conducting part. The metal ring structure that contacts the external heat-conducting component is used for heat conduction to ensure that the paraffin melts quickly, but this increases the complexity of the components of the microfluidic chip or detection system and other problems that may arise, such as the assembly and matching process of the metal ring and the surrounding component materials, sealing problems, and cost problems. A Chinese invention patent with publication number CN114591812A discloses a bioreactor chip and a centrifugal microfluidic system. Some chambers of the chip involved are connected by paraffin valves, and the paraffin valves are opened under heating and centrifugal force. In order to effectively reduce the conditions required for centrifugal release and ensure that the liquid in the upstream chamber can smoothly break through the paraffin valve that still has a certain viscosity after melting, the scheme designs and loads auxiliary steel balls in the upstream chamber of the corresponding paraffin valve. After the auxiliary steel balls are electromagnetically heated by the additional built-in coil of the system, they can break through the paraffin valve under a smaller centrifugal force. However, the design of the auxiliary steel balls and coil components also increases the complexity and manufacturing cost of the microfluidic chip system. The Chinese invention patent with the publication number CN111269826A discloses a fully enclosed microfluidic test kit, which has multiple hot-melt paraffin valves located on the liquid channel and the gas channel inside, which are used for mutual isolation and liquid controlled release between the chambers. The chip test kit as a whole is a fully enclosed structure formed by the integrated bonding and sealing of three channel layers, wherein the organic high molecular polymer film layer located in the middle forms a sealing bond with the gas channel layer located on the outside and the liquid channel layer located on the innermost side, respectively, to ensure the good isolation between the chambers and the channels before the paraffin valve melts, and the complete sealing of the chip as a whole after the paraffin valve melts. The three-layer channel bonding and sealing design of this scheme is extremely important to ensure the reliable isolation of the paraffin valve and the sealing of the chip, so it has high requirements for the interlayer bonding process. At the same time, since the paraffin is easy to shrink when it cools and solidifies to produce a certain degree of cavity or bubble, which leads to the weakening of the airtightness of the paraffin valve, the design of multiple paraffin valves for sealing and isolation in this design is also very easy to cause crosstalk between chambers, leakage and other problems.

[0005] At the same time, the paraffin valve structures disclosed in the above-mentioned prior art all face the same problem - they can only be used once from closed to open, and cannot realize controllable multiple switching functions, which results in the liquid in its upstream chamber being released only once, thus limiting the application prospects of the paraffin valve in controllable batch release, precise quantitative release, etc., making the paraffin valve still have greater limitations in functional expansion compared to other active control valves. Summary of the invention

[0006] To solve the above problems, the object of the present invention is to provide a centrifugal microfluidic chip and a preparation method thereof. It mainly consists of a "three-way" switching pipeline, a phase change material and an energy storage device connected thereto, which can conveniently realize the controllable batch release and accurate quantitative release of the upstream liquid. Its structural composition is simple, which is convenient for reducing the production and manufacturing costs and simplifying the complexity of fluid controlled release.

[0007] The present invention adopts the following technical solutions.

[0008] A centrifugal microfluidic chip, comprising: a chip body; a first reaction chamber, the first reaction chamber is located on the chip body and close to the rotation center of the chip body; a second reaction chamber, the second reaction chamber is located on the chip body and farther from the rotation center than the first reaction chamber; a fluid switching valve, the fluid switching valve is connected to the first reaction chamber and the second reaction chamber, and the fluid switching valve can repeatedly close or communicate the first reaction chamber and the second reaction chamber under the conditions of the rotation and heating of the chip body.

[0009] Further, the fluid switching valve includes: an energy storage device; a switching pipeline, the distal end of the switching pipeline is communicated with the energy storage device, and the proximal ends of the switching pipeline are respectively communicated with the first reaction chamber and the second reaction chamber; a phase change material, the phase change material is filled in the switching pipeline for sealing the energy storage device.

[0010] Further, the switching pipeline includes: a first flow channel, one end of the first flow channel is communicated with the first reaction chamber; a second flow channel, the distal end of the second flow channel is communicated with the energy storage device, the proximal end of the second flow channel is communicated with the first flow channel, and the angle between the second flow channel and the radial direction with the rotation center as the center of the circle is greater than 30°; a third flow channel, one end of the third flow channel is communicated with the second reaction chamber, the other end of the third flow channel is communicated with the second flow channel, and the middle part of the third flow channel is bent toward the rotation center.

[0011] Further, the switching pipeline includes: a connecting pipeline, one end of the connecting pipeline is communicated with the distal end of the second flow channel, and the other end of the connecting pipeline is communicated with the side of the energy storage device away from the rotation center.

[0012] Further, the energy storage device includes: an energy storage cavity; an elastic diaphragm, the elastic diaphragm and part or all of the energy storage cavity form a sealed cavity.

[0013] Further, a buffer portion is provided on one side of the switching pipeline close to the energy storage device; the buffer portion is in the shape of a flow channel, the buffer portion communicates with the second flow channel, and the included angle between the end of the buffer portion close to the energy storage device and the second flow channel towards the rotation center is smaller than the included angle between the end of the buffer portion far from the energy storage device and the second flow channel towards the rotation center; the included angle between the end of the buffer portion far from the energy storage device and the second flow channel towards the rotation center is not greater than 90°.

[0014] Further, the relationship between the diameter D1 of the buffer portion and the diameter D2 of the second flow channel satisfies:

[0015] ;

[0016] The included angle between the end of the buffer portion far from the energy storage device and the second flow channel towards the rotation center and the included angle between the end of the buffer portion close to the energy storage device and the second flow channel towards the rotation center satisfy the following relationship:

[0017] .

[0018] Further, a storage cavity is further included, and the storage cavity is used for placing phase change materials. The storage cavity communicates with the first flow channel or the third flow channel through a fourth flow channel; the end of the fourth flow channel close to the rotation center communicates with the distal end of the storage cavity; the end of the fourth flow channel far from the rotation center communicates with the first flow channel or the third flow channel; the connection position of the fourth flow channel and the first flow channel or the third flow channel forms an obtuse angle with the radial direction centered on the rotation center on the projection of the flow channel on the side far from the rotation center towards the fluid switching valve.

[0019] Further, the shortest distance between the connection point of the first flow channel and the first reaction chamber and the rotation center is greater than the shortest distance at the bottom of the bent portion of the third flow channel far from the rotation center.

[0020] Further, the diameter of the fourth flow channel is smaller than the diameters of the first flow channel, the second flow channel, and the third flow channel.

[0021] Further, the diameter of the fourth flow channel is more than 5% smaller than the diameter of the smallest flow channel among the first flow channel, the second flow channel, and the third flow channel.

[0022] Further, a heating portion is further included, and the heating portion is arranged below the fluid switching valve, the fourth flow channel, and the storage cavity; the heating portion includes: a first heating portion arranged below the fluid switching valve; a second heating portion arranged below the storage cavity and the fourth flow channel connected thereto.

[0023] The present invention also provides a method for preparing a centrifugal microfluidic chip, wherein a closable opening is provided at a preset position of the energy storage cavity; the method includes the following steps: heating the first heating part and the second heating part, rotating the centrifugal microfluidic chip, and melting a part of the phase change material to flow into the energy storage cavity corresponding to the first heating part or a part of the switching pipeline communicating with the energy storage cavity; stopping heating the second heating part, after the excess part of the melted phase change material is thrown out from the closable opening, closing the closable opening; heating the first heating part and the second heating part to fill the other parts of the fluid switching valve; after the filling is completed, stopping heating the second heating part, stopping heating the first heating part when there are no bubbles in the melted phase change material, and stopping rotation after the melted phase change material solidifies, and that's it.

[0024] Further, a vent hole is provided at a preset position of the energy storage cavity, and the method includes the following steps: heating the first heating part and the second heating part, rotating the centrifugal microfluidic chip, and melting the phase change material to flow into the fluid switching valve; after the filling is completed, stopping heating the second heating part, stopping heating the first heating part when there are no bubbles in the melted phase change material, and stopping rotation after the melted phase change material solidifies, and that's it.

[0025] The present invention provides a centrifugal microfluidic chip and a method for preparing the same. Compared with the prior art, the present invention has the following beneficial technical effects:

[0026] (1) First, by controlling two conditions of centrifugal force and heating, the repeated connection and closing of the fluid switching valve are realized. The sequential dropping of the reaction solution ensures the normal progress of the reaction process. And by closing the fluid switching valve, it is ensured that the reaction in the second reaction chamber will not be affected by the liquid in the first reaction chamber. The controllable batch release and precise quantitative release of the upstream liquid make the detection result more accurate.

[0027] (2) Second, the stable centrifugal force at a certain rotation speed and the constant gas pressure generated by the volume change are used to control the opening and closing of the valve, making the valve control method more efficient, stable and reliable; based on the balance relationship between the centrifugal force and the gas pressure, the paraffin valve structure can be opened and closed multiple times, and then the batch release and precise quantitative release of the liquid reagent can be controlled, making the microfluidic chip design more functional and meeting various microfluidic control requirements; the paraffin valve structure that can be opened and closed multiple times has a simple composition and an efficient and concise operation process, with extremely low requirements for operators and the hardware system, avoiding the complex components and operation processes of other active valve control methods. Description of the Drawings

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the accompanying drawings required for the description of the embodiments. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can be obtained based on these drawings.

[0029] Figure 1 Structural diagram of a centrifugal microfluidic chip provided for Embodiment 1 of the present invention;

[0030] Figure 2 Schematic diagram of a switching pipeline structure provided for Embodiment 1 of the present invention;

[0031] Figure 3 Schematic diagram of a buffer part structure provided for Embodiment 1 of the present invention;

[0032] Figure 4 Structural diagram of a centrifugal microfluidic chip with a storage cavity provided for Embodiment 1 of the present invention;

[0033] Figure 5 For Figure 4 Partial enlarged view;

[0034] Figure 6 Schematic diagram of a structure with a heating part provided for Embodiment 1 of the present invention;

[0035] Figure 7 First state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 2 of the present invention;

[0036] Figure 8 Second state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 2 of the present invention;

[0037] Figure 9 Third state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 2 of the present invention;

[0038] Figure 10 Fourth state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 2 of the present invention;

[0039] Figure 11 First state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 3 of the present invention;

[0040] Figure 12 Second state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 3 of the present invention;

[0041] Figure 13 Third state diagram of a centrifugal microfluidic chip during filling provided for Embodiment 3 of the present invention;

[0042] Figure 14It is the first state diagram during the filling of the centrifugal microfluidic chip provided in Embodiment 4 of the present invention.

[0043] Figure 15 It is the second state diagram during the filling of the centrifugal microfluidic chip provided in Embodiment 4 of the present invention;

[0044] Figure 16 It is the third state diagram during the filling of the centrifugal microfluidic chip provided in Embodiment 4 of the present invention.

[0045] Reference numerals: 20, first reaction chamber; 21, second reaction chamber; 22, fluid switching valve; 220, energy storage device; 2200, energy storage chamber; 2201, piston; 2202, elastic diaphragm; 2203, closable opening; 2204, ventilation hole; 23, buffer part; 24, storage chamber; 240, fourth flow channel; 2210, first flow channel; 2211, second flow channel; 2212, third flow channel; 221, switching pipeline; 222, phase change material; 223, connecting pipeline; 250, first heating part; 251, second heating part. Detailed implementation manners

[0046] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. Usually, the components of the embodiments of the present invention described and illustrated in the accompanying drawings here can be arranged and designed in various different configurations.

[0047] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed present invention, but merely represents the selected embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0048] It should be noted that: similar reference numerals and letters denote similar items in the following drawings. Therefore, once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings.

[0049] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by terms such as "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, or the orientation or positional relationship in which the inventive product is customarily placed during use. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation to the present invention. In addition, terms such as "first", "second", "third", etc. are only used for distinguishing descriptions and cannot be construed as indicating or implying relative importance.

[0050] In the description of the present invention, it should also be noted that unless otherwise clearly specified and defined, the terms "set", "installed", "connected", "coupled" 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 directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0051] Embodiment 1

[0052] An embodiment of the present invention discloses a centrifugal microfluidic chip, as Figure 1 shown, comprising: a chip body; a first reaction chamber 20, the first reaction chamber 20 is located on the chip body and close to the rotation center O of the chip body; a second reaction chamber 21, the second reaction chamber 21 is located on the chip body and farther from the rotation center O than the first reaction chamber 20; a fluid switching valve 22, the fluid switching valve 22 is connected to the first reaction chamber 20 and the second reaction chamber 21, and the fluid switching valve 22 can repeatedly close or communicate the first reaction chamber 20 and the second reaction chamber 21 under the conditions of the rotation and heating of the chip body.

[0053] An installation hole is provided on the chip body for connection with the device. Under the drive of the device, the chip body is driven to rotate. The first reaction chamber 20 and the second reaction chamber 21 are in an upstream-downstream relationship. The liquid in the first reaction chamber 20 is dropped into the second reaction chamber 21 multiple times to complete the relevant reaction. The first reaction chamber 20 and the second reaction chamber 21 can be any step in the steps required in the biochemical reaction for the transfer or reaction of the liquid. The first reaction chamber 20 and the second reaction chamber 21 can be provided with corresponding reagents or magnetic beads for accelerating the reaction inside based on specific reaction conditions, which will not be elaborated here.

[0054] The centrifugal microfluidic chip provided by the present invention, first, realizes the repeated connection and closing of the fluid switching valve 22 by controlling two conditions of centrifugal force and heating, and the sequential dropping of the reaction solution ensures the normal progress of the reaction process. Moreover, by closing the fluid switching valve 22, it is ensured that the reaction in the second reaction chamber 21 will not be affected by the liquid in the first reaction chamber 20. The controllable batch release and precise quantitative release of the upstream liquid make the detection result more accurate. Secondly, the stable centrifugal force at a certain rotational speed and the constant gas pressure generated by the volume change are used to control the opening and closing of the valve, making the valve control method more efficient, stable and reliable; based on the balance relationship between the centrifugal force and the gas pressure, the paraffin valve structure can be switched on and off multiple times, and then the batch release and precise quantitative release of the liquid reagent can be controlled, making the design of the microfluidic chip more functional and meeting various microfluidic control requirements; the paraffin valve structure that can be switched on and off multiple times has a simple composition, an efficient and concise operation process, and extremely low requirements for operators and the hardware system, avoiding the complex components and operation processes of other active valve control methods.

[0055] Specifically, as Figure 1 shown, the fluid switching valve 22 includes: an energy storage device 220; a switching pipeline 221, the distal end of the switching pipeline 221 is communicated with the energy storage device 220, and the proximal end of the switching pipeline 221 is respectively communicated with the first reaction chamber 20 and the second reaction chamber 21; a phase change material 222, and the phase change material 222 is filled in the switching pipeline 221 for sealing the energy storage device 220.

[0056] In the present invention, the "distal end" and "proximal end" are defined with respect to the rotation center O. In the present invention, the energy storage device 220 is an energy storage structure, and its function is that after the phase change material 222 is heated and transformed into a liquid state, the chip body rotates, and the liquid phase change material is extruded by the centrifugal force to form potential energy; when the rotational speed of the microfluidic chip decreases, the potential energy of the energy storage device is released to push the liquid phase change material 222 to move in the direction close to the rotation center O.

[0057] The energy storage device has various structures, such as Figure 2 shown, the energy storage device 220 includes an energy storage chamber 2200 and a piston 2201. Under the action of centrifugal force, the liquid phase change material 222 directly or indirectly extrudes the piston 2201, thereby compressing the sealed space formed by the energy storage chamber 2200 and the piston 2201 to form potential energy; it should be noted that the piston 2201 can be replaced by an elastic diaphragm. Specifically, the periphery of the elastic diaphragm is fixedly and hermetically connected to the inner wall of the energy storage chamber 2200, and the elastic diaphragm and the energy storage chamber 2200 form a sealed space for subsequent energy storage.

[0058] In another embodiment, as Figure 1As shown, the fluid switching valve 22 further includes a bent connecting pipe 223. One end of the connecting pipe 223 communicates with the distal end of the second flow channel 2211, and the other end of the connecting pipe 223 is connected to the side of the energy storage device 220 away from the rotation center O. The energy storage device 220 may be an energy storage cavity 2200. At this time, there is no need to provide a piston in the energy storage cavity 2200, and the structure is simple, saving manufacturing costs. Under the action of centrifugal force, the liquid phase change material 222 enters the energy storage cavity 2200, and forms a sealed cavity with the energy storage cavity 2200. Under the action of centrifugal force, the energy storage chamber is compressed to store energy. Preferably, an elastic diaphragm is provided in the energy storage cavity 2200. Specifically, the periphery of the elastic diaphragm is fixedly and sealingly connected to the inner wall of the energy storage cavity 2200, and the elastic diaphragm and the energy storage cavity 2200 form a sealed space for subsequent energy storage.

[0059] The phase change material 222 in the present invention may be wax. For example, the wax may be paraffin wax, microcrystalline wax, synthetic wax or natural wax. Alternatively, the phase change material 222 may also be a gel or a thermoplastic resin. The gel may be polyacrylamide, polyacrylate, polymethacrylate, or polyvinylamine. The thermoplastic resin may be cyclic olefin copolymer (COC), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS), polyoxymethylene (POM), perfluoroalkoxy (PFA), polyvinyl chloride (PVC), polypropylene (PP), polyethylene terephthalate (PET), polyetheretherketone (PEEK), polyacrylate (PA), polysulfone (PSU) or polyvinylidene fluoride (PVDF), etc.

[0060] Specifically, as Figure 2As shown in the figure, the switching pipeline 221 includes: a first flow channel 2210, one end of the first flow channel 2210 is communicated with the first reaction chamber 20; a second flow channel 2211, the distal end of the second flow channel 2211 is communicated with the energy storage device 220, the proximal end of the second flow channel 2211 is communicated with the first flow channel 2210, and the included angle γ between the second flow channel 2211 and the radial direction R with the rotation center O as the center of the circle is greater than 30°; a third flow channel 2212, one end of the third flow channel 2212 is communicated with the second reaction chamber 21, and the other end of the third flow channel 2212 is communicated with the second flow channel 2211, and the middle part of the third flow channel 2212 is bent towards the rotation center O. By making the included angle γ between the second flow channel 2211 and the radial direction R with the rotation center O as the center of the circle greater than 30°, it is ensured that the impact force of the liquid flowing out of the first reaction chamber 20 is mainly applied to the inner wall of the flow channel, buffering and weakening the impact force, preventing the liquid from directly applying the impact force to the phase change material, resulting in part of the phase change material being transported to the second reaction chamber 21, reducing the amount of phase change material in the fluid switching valve 22, and reducing the number of repeated uses during subsequent use. Secondly, the middle part of the third flow channel 2212 is bent towards the rotation center O, which can ensure that when the centrifugal microfluidic chip is subsequently prepared, the excess phase change material enters the first reaction chamber 20 instead of the second reaction chamber 21. The beneficial technical effects will be described in detail later.

[0061] It should be noted that there are still some problems in the above technical solution, that is, after the energy storage device 220 finishes energy storage, when the chip body stops rotating or the rotation speed decreases, and the phase change material is in a liquid state, there is a possibility that the energy stored in the energy storage device 220 is fully released in a short time, resulting in the liquid phase change material fluctuating back and forth at the preset position of the liquid phase change material at the equilibrium air pressure. If the energy release speed is too short and the fluctuation is large, part of the phase change material will enter the first reaction chamber 20 or the second reaction chamber 21. On the one hand, the present invention sets the third flow channel communicated with the second reaction chamber 21 to be bent towards the rotation center O to prevent the fluctuating liquid phase change material from entering the second reaction chamber 21 and not being recoverable. The closest distance from the bottom of the bent part of the third flow channel 2212 to the rotation center is less than the closest distance from the connection position of the first reaction chamber 20 and the first flow channel 2210 to the rotation center O. The overshoot liquid phase change material enters the first reaction chamber 20 and is then recovered by the fluid switching valve 22.

[0062] In order to suppress the influence brought by the above overshoot, such as Figure 3As shown, a buffer portion 23 is provided on one side of the switching pipeline 221 close to the energy storage device 220; the buffer portion 23 is in the shape of a flow channel, the buffer portion 23 communicates with the second flow channel 2211, and the included angle between one end of the buffer portion 23 close to the energy storage device 220 and the second flow channel 2211 toward the rotation center O side is smaller than the included angle between one end of the buffer flow channel far from the energy storage device and the second flow channel toward the rotation center side ; the included angle between one end of the buffer portion 23 far from the energy storage device 220 and the second flow channel 2211 toward the rotation center side is not greater than 90°. By defining less than it is ensured that when the liquid phase change material flows through the buffer portion 23, it preferentially flows in from one end close to the energy storage device 220 and flows out from one end far from the energy storage device 220, and not being greater than 90° ensures that the flow direction S2 of the liquid phase change material in the buffer portion buffers the oncoming flow direction S1 in the second flow channel 2211, reduces the energy release peak value of the energy storage device 220, and prevents the reduction of the reuse times of the fluid switching valve 22 caused by the overshoot of the liquid phase change material.

[0063] It should be noted that the buffer wave peak of the liquid phase change material can be reduced by setting the buffer portion, but it cannot be reduced too much, resulting in a long occupation time for the closing and connection of the fluid switching valve 22 and low efficiency. To solve the above problems, the relationship between the diameter D1 of the buffer portion and the diameter D2 of the second flow channel 2211 satisfies:

[0064] ;

[0065] The included angle between one end of the buffer portion far from the energy storage device and the second flow channel toward the rotation center side and the included angle between one end of the buffer portion close to the energy storage device and the second flow channel toward the rotation center side satisfies the following relationship:

[0066] .

[0067] It should be noted that when the cross-section of the buffer portion 23 or the second flow channel 2211 is not circular, the equivalent diameter can be calculated through its cross-sectional area.

[0068] It can be understood that one or more buffer portions 23 can be provided in the present invention to increase the buffering of the liquid phase change material and prevent its overshoot. It can be provided at any position of the second flow channel 2211. As a preferred embodiment of the present invention, one buffer portion 23 is provided, and the opening and closing times of the prepared fluid switching valve 22 are ensured to be within 1 second through the above size limitation, and no overshoot problem will occur.

[0069] Further, as shown in Figure 4 and 5 , the centrifugal microfluidic chip further includes a storage cavity 24 for placing a phase change material. The storage cavity 24 communicates with the first flow channel 2210 or the third flow channel 2212 through a fourth flow channel 240. One end of the fourth flow channel 240 close to the rotation center O communicates with the distal end of the storage cavity 24. One end of the fourth flow channel 240 away from the rotation center O communicates with the first flow channel 2210 or the third flow channel 2212. The included angle α between the connection position of the fourth flow channel 240 and the first flow channel 2210 or the third flow channel 2212 and the radial direction R with the rotation center O as the center point, projected onto the flow channel on the side away from the rotation center O by the rotation center O, is an obtuse angle towards the fluid switching valve. Through the above settings, it is ensured that the phase change material in the storage cavity 24 fills the switching pipeline 221 in the fluid switching valve 22 under the action of heating and centrifugation, preventing the liquid phase change material from flowing into the second reaction chamber 21 and causing waste.

[0070] It should be noted that the storage cavity 24 in this application is used to store the phase change material. Before the centrifugal microfluidic chip performs detection, the phase change material needs to be filled into the fluid switching valve 22 to empower the fluid switching valve 22. After the filling is completed, biochemical reactions and operations can be carried out, etc.

[0071] Specifically, as shown in Figure 5 , the shortest distance S4 between the connection point of the first flow channel 2210 and the first reaction chamber 20 and the rotation center O is greater than the shortest distance S5 at the bottom of the bent portion of the third flow channel 2212 away from the rotation center. If the phase change material in the storage cavity 24 is excessive, the excess phase change material flows through the first flow channel 2210 to the first reaction chamber 20, and finally flows through the second flow channel 2211 to the second reaction chamber 21. The phase change material flowing into the first reaction chamber 20 can supplement the phase change material in the subsequent fluid switching valve 22, increasing the number of times the fluid switching valve 22 can be reused.

[0072] Specifically, the diameter of the fourth flow channel 240 is smaller than those of the first flow channel 2210, the second flow channel 2211, and the third flow channel 2212. When the phase change material in the storage cavity 24 is heated and melted, it enters the second flow channel 2211 through the fourth flow channel 240 and flows towards the distal end along the side wall of the second flow channel 2211 away from the center of the circle. If the diameter of the fourth flow channel is the same as that of the second flow channel, the gas accumulated in the switching pipe 22 and the energy storage device 220 cannot be completely discharged, resulting in the inability of the liquid phase change material to completely fill the switching pipe 22. Additionally, it will cause excessive air pressure inside the energy storage cavity 2200, affecting the valve control effect. The diameter of the fourth flow channel 240 being smaller than those of the first flow channel 2210, the second flow channel 2211, and the third flow channel 2212 can ensure that the fine liquid flow of the liquid phase change material flows towards the distal end along the side wall of the second flow channel 2211 away from the center of the circle. Meanwhile, it is beneficial for the gas in the fluid switching valve 22 to be discharged along the side wall of the second flow channel 2211 closer to the center of the circle.

[0073] Specifically, the diameter of the fourth flow channel is more than 5% smaller than that of the flow channel with the smallest diameter among the first flow channel, the second flow channel, and the third flow channel. Through the above size limitation, the gas discharge efficiency in the fluid switching valve 22 is high, and the preparation time of the fluid switching valve 22 is short.

[0074] As Figure 6 shown, the centrifugal chip proposed by the present invention further includes a heating part, which is arranged below the fluid switching valve 22, the fourth flow channel 240, and the storage cavity 24, and includes: a first heating part 250, arranged below the fluid switching valve 22; a second heating part 251, which is arranged below the storage cavity 24 and the connected fourth flow channel 240.

[0075] The heating part is made of a material with a relatively high thermal conductivity, such as copper and silver, or directly uses a heating element.

[0076] Embodiment 2

[0077] The embodiment of the present invention further provides a preparation method for the above-mentioned centrifugal microfluidic chip, including:

[0078] A closable opening 2203 is provided at a preset position in the energy storage cavity; it should be noted that the closable opening is an opening that can be opened or closed under manual or automatic control. In engineering practice, it is difficult to fill the U-shaped structure at the bottom of the fluid switching valve 22, especially on one side of the U-shaped structure far from the second flow channel 2211. To solve the above problem, a closable opening 2203 can be provided on the energy storage cavity 2200. The setting position of the closable opening can be based on the required pressure value, calculate the volume that needs to be sealed, and thus determine the position of the opening.

[0079] As Figure 7As shown, the initial state is that the storage cavity 24 is filled with solid phase change material;

[0080] It includes the following steps:

[0081] Heat the first heating part 250 and the second heating part 251, rotate the centrifugal microfluidic chip, and part of the phase change material melts and flows into the energy storage cavity corresponding to the first heating part 250 or the partial switching pipeline communicating with the energy storage cavity, as Figure 8 shown;

[0082] Stop heating the second heating part 251. After the excess part of the partially melted phase change material is thrown out from the closable opening, close the closable opening 2203, as Figure 9 shown;

[0083] Heat the first heating part 250 and the second heating part 251 to fill the other parts of the fluid switching valve 22; after the filling is completed, stop heating the second heating part 251. When there are no bubbles in the melted phase change material, stop heating the first heating part 250. After the melted phase change material solidifies, stop rotating, and that's it, as Figure 10 shown.

[0084] Embodiment 3

[0085] In this embodiment, as Figure 11 shown, the energy storage device 220 includes: an energy storage cavity 2200; an elastic diaphragm 2202, and the elastic diaphragm 2202 and part or all of the energy storage cavity 2200 form a sealed chamber.

[0086] The preparation method of the centrifugal microfluidic chip prepared in this embodiment is as follows:

[0087] As Figure 11 shown, the initial state is that the storage cavity 24 is filled with solid phase change material;

[0088] Heat the first heating part 250 and the second heating part 251. When the liquid phase change material completely fills the fluid switching valve 22, close the second heating part 251, as Figure 12 shown;

[0089] When there are no bubbles in the melted phase change material, stop heating the first heating part 250. After the melted phase change material solidifies, stop rotating, and that's it, as Figure 13 shown.

[0090] Embodiment 4

[0091] The embodiment of the present invention also provides a preparation method for the above-mentioned centrifugal microfluidic chip, including:

[0092] The energy storage cavity is provided with a vent hole 2204 at a preset position; the vent hole 2204 only allows gas to pass through while preventing the phase change material from passing through, for the same reason as in Embodiment 2, that is, in engineering practice, it is difficult to fill the U-shaped structure at the bottom of the fluid switching valve 22, especially on one side of the U-shaped structure far from the second flow channel 2211. To solve the above problems, it is only necessary to set a vent hole 2204 on the energy storage cavity 2200. The setting position of the vent hole can be based on the required pressure value to calculate the volume that needs to be sealed, so as to determine the opening position.

[0093] As Figure 14 shown, the initial state is that the storage cavity 24 is filled with a solid phase change material;

[0094] It includes the following steps:

[0095] Heat the first heating part 250 and the second heating part 251, and rotate the centrifugal microfluidic chip. The phase change material melts and flows into the fluid switching valve. As Figure 15 shown, since the vent hole 2204 only allows gas to pass through, there is no filling resistance when the melted phase change material is at a radius with the rotation center O as the center and the rotation center O and the vent hole 2204. When the melted phase change material crosses the vent hole 2204, potential energy is generated to push the liquid phase change material to close the switching pipeline 221;

[0096] After the filling is completed, stop heating the second heating part 251. When there are no bubbles in the melted phase change material, stop heating the first heating part 250. After the melted phase change material solidifies, stop rotating, and that's it. As Figure 16 shown.

[0097] Embodiment 5

[0098] The specific experimental process is as follows:

[0099] First, add 2 mL of tetraethyl orthosilicate (TEOS) to the first reaction chamber 20;

[0100] Secondly, uniformly disperse 0.5 g of superparamagnetic nanoparticles (Fe3O4) in a mixed solution of concentrated ammonia water (0.45 mL, 25 wt%) and absolute ethanol (9 mL, 99% purity), inject it into the second reaction chamber 21, and keep stirring evenly;

[0101] Heat the first heating part and the second heating part until the paraffin melts, rotate the chip body to 2000 rpm, connect the first flow channel 2210 and the third flow channel 2212, inject 0.2 ml of tetraethyl orthosilicate (TEOS) from the first reaction chamber 20 into the second reaction chamber 21, then reduce the rotation speed of the chip body to 500 rpm, close the communication channel between the first reaction chamber 20 and the second reaction chamber 21 with the fluid switching valve 22, after reacting for 10 min, repeat the above control;

[0102] After the dropping is completed, continuously stir thoroughly for 12 h. After sufficient reaction, superparamagnetic silica nanoparticles are generated. After washing, they can be used for nucleic acid extraction.

[0103] The above are only the embodiments of the present application and are not used to limit the protection scope of the present application. For those skilled in the art, the present application can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included within the protection scope of the present application.

Claims

1. A centrifugal microfluidic chip, characterized in that: include: Chip body; A first reaction chamber, the first reaction chamber is located on the chip body and close to the rotation center of the chip body; a second reaction chamber, the second reaction chamber being located on the chip body and being farther from the rotation center than the first reaction chamber; A fluid switching valve, the fluid switching valve is connected to the first reaction chamber and the second reaction chamber, and the fluid switching valve can repeatedly close or connect the first reaction chamber and the second reaction chamber under the conditions of rotation and heating of the chip body; The fluid switching valve comprises: Energy storage device; A switching pipeline, wherein the distal end of the switching pipeline is connected to the energy storage device, and the proximal end of the switching pipeline is connected to the first reaction chamber and the second reaction chamber respectively; Phase change material, the phase change material is filled in the switching pipe to seal the energy storage device.

2. The centrifugal microfluidic chip according to claim 1, characterized in that: The switching pipeline comprises: a first flow channel, one end of which is in communication with the first reaction chamber; a second flow channel, wherein a distal end of the second flow channel is connected to the energy storage device, a proximal end of the second flow channel is connected to the first flow channel, and an angle between the second flow channel and a radial direction with the rotation center as the center is greater than 30°; A third flow channel, one end of the third flow channel is communicated with the second reaction chamber, the other end of the third flow channel is communicated with the second flow channel, and the middle portion of the third flow channel is bent toward the rotation center.

3. The centrifugal microfluidic chip according to claim 2, characterized in that: The switching pipeline comprises: A connecting pipe, one end of which is connected to the distal end of the second flow channel, and the other end of which is connected to a side of the energy storage device away from the rotation center.

4. The centrifugal microfluidic chip according to claim 1 or 3, characterized in that: The energy storage device comprises: Energy storage chamber; An elastic diaphragm, wherein the elastic diaphragm and part or all of the energy storage chamber form a sealed chamber.

5. The centrifugal microfluidic chip according to claim 1, characterized in that: A buffer portion is provided on one side of the switching pipe close to the energy storage device; The buffer portion is in the shape of a flow channel, the buffer portion is connected to the second flow channel, and the angle between the end of the buffer portion close to the energy storage device and the second flow channel toward the rotation center is smaller than the angle between the end of the buffer portion away from the energy storage device and the second flow channel toward the rotation center; The angle between the end of the buffer portion away from the energy storage device and the second flow channel toward the rotation center is no greater than 90°.

6. The centrifugal microfluidic chip according to claim 5, characterized in that: The relationship between the diameter D1 of the buffer portion and the diameter D2 of the second flow channel satisfies: The relationship between the angle λ2 between the end of the buffer portion away from the energy storage device and the second flow channel toward the rotation center and the angle λ1 between the end of the buffer portion close to the energy storage device and the second flow channel toward the rotation center satisfies: 5°≤λ2-λ1≤30°.

7. The centrifugal microfluidic chip according to claim 2, characterized in that: It also includes a storage cavity, the storage cavity is used to place the phase change material, and the storage cavity is connected with the first flow channel or the third flow channel through the fourth flow channel; An end of the fourth flow channel close to the rotation center is connected to the distal end of the storage cavity; an end of the fourth flow channel away from the rotation center is connected to the first flow channel or the third flow channel; The angle between the projection of the connection position of the fourth flow channel with the first flow channel or the third flow channel on the flow channel away from the rotation center and the radial direction with the rotation center as the center toward the fluid switching valve is an obtuse angle.

8. The centrifugal microfluidic chip according to claim 7, characterized in that: The shortest distance between the connection point between the first flow channel and the first reaction chamber and the rotation center is greater than the shortest distance away from the bottom of the third flow channel bending portion of the rotation center.

9. The centrifugal microfluidic chip according to claim 8, characterized in that: The fourth flow channel has a smaller diameter than the first flow channel, the second flow channel, and the third flow channel.

10. The centrifugal microfluidic chip according to claim 9, characterized in that: The diameter of the fourth flow channel is smaller than the smallest diameter of the first flow channel, the second flow channel and the third flow channel by more than 5%.

11. The centrifugal microfluidic chip according to claim 9, characterized in that: It also includes a heating part, which is arranged on the fluid switching valve, the fourth flow channel and the lower part of the storage chamber; The heating part includes: a first heating part, which is arranged below the fluid switching valve; and a second heating part, which is arranged below the storage cavity and a fourth flow channel connected thereto.

12. A method for preparing a centrifugal microfluidic chip as claimed in claim 11, characterized in that: A closable opening is provided at a preset position of the energy storage chamber; The steps include: The first heating part and the second heating part are heated, and the centrifugal microfluidic chip is rotated, so that part of the phase change material melts and flows into the energy storage cavity corresponding to the first heating part or part of the switching pipeline connected to the energy storage cavity; The heating of the second heating part is stopped, and the excess part of the partially melted phase change material is thrown out from the closable opening, and then the closable opening is closed; heating the first heating part and the second heating part to fill other parts of the fluid switching valve; After the filling is completed, the heating of the second heating part is stopped. When there are no bubbles in the melted phase change material, the heating of the first heating part is stopped. After the melted phase change material solidifies, the rotation is stopped.

13. A method for preparing a centrifugal microfluidic chip as claimed in claim 11, characterized in that: The energy storage chamber is provided with a vent hole at a preset position, and the steps include: heating the first heating part and the second heating part, rotating the centrifugal microfluidic chip, and causing the phase change material to melt and flow into the fluid switching valve; After the filling is completed, the heating of the second heating part is stopped. When there are no bubbles in the melted phase change material, the heating of the first heating part is stopped. After the melted phase change material solidifies, the rotation is stopped.

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