Fishbone-tesla valve micro-mixing chip and preparation method and application thereof

Abstract

The application discloses a fishbone-Tesla valve micro-mixing chip and a preparation method and application thereof. The micro-mixing chip comprises a chip body, a Tesla valve and at least two mixing inlets. The Tesla valve comprises at least one mixing unit. The mixing inlets are communicated with the unit inlets of the outermost mixing units. At least one mixing unit in the Tesla valve is provided with at least one fishbone structure. The sharp corners of the fishbone structure face the mixing inlets. At least one fishbone structure is arranged in the Tesla valve. The sharp corners of the fishbone structure face the mixing inlets. When fluid flows through the fishbone structure in the Tesla valve, the fishbone structure disperses the fluid in the Tesla valve to flow to both sides, promotes the lateral flow of the fluid, and thus improves the mixing efficiency of the micro-mixing chip.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of micro mixing, and particularly relates to a fishbone-Tesla valve micro mixing chip and a preparation method thereof. BACKGROUND

[0002] As an important part of microfluidic technology, micro mixing chips are widely used in chemical reactions, medical detection, environmental monitoring, material synthesis, etc. due to their excellent mixing efficiency. Compared with macroscopic reaction systems, micro mixing chips require less fluid volume, which can significantly reduce the use of reagents and the generation of waste, reduce experimental costs and environmental impact. In addition, micro mixing chips can achieve mixing in a short time, which is suitable for the demand of rapid reaction, shortens the reaction time and improves the experimental efficiency. Due to the small size of micro mixing chips, they can be integrated into portable devices, and can also be combined with other microfluidic devices to form an integrated and multifunctional reaction system.

[0003] Due to the micron or nanoscale limitations, the fluid in the micro mixing chip flows in a laminar flow manner, so the mixing between different fluids is mainly completed by molecular diffusion. In order to improve the mixing efficiency, different mixing methods and micro mixing chip structures have been proposed. At present, micro mixing chips are divided into active and passive micro mixing chips according to whether they need external energy input. Active micro mixing chips need external energy input, including electricity, magnetic field, acoustics, heat and pressure, etc. to improve the mixing efficiency. Although the active micro mixing chip has more precise control over the fluid, its structure is complex, and the introduced energy field has an additional effect on the flow state of the fluid. Passive micro mixing chips complete the mixing of different types of fluids through special structure flow channels, and have been widely studied due to the advantages of low cost, easy integration and no need for external energy input. According to the different mixing principles, passive micro mixing chips are divided into micro mixing chips relying on Dean vortex mixing, micro mixing chips based on contraction and expansion effect mixing, micro mixing chips with split and recombination (SAR) structure and micro mixing chips relying on spiral flow mixing, etc. The mixing mechanism includes introducing laminar and forming chaotic advection in the channel.

[0004] The Tesla micro mixing chip belongs to the micro mixing chip with SAR structure, and each mixing unit is composed of two unbalanced sub-channels. Due to the Coanda effect, the fluid in the curved sub-channel is split and then recombined with the fluid in the other sub-channel. The transverse flow and chaotic convection generated by the collision between the fluids promote the mixing. In the prior art, genetic algorithm is used for shape and structure optimization design, and better performance than the original Tesla micro mixing chip is obtained. However, the mixing efficiency of the Tesla micro mixing chip in the prior art still needs to be further improved.

[0005] Therefore, the prior art still needs to be improved and developed. SUMMARY

[0006] The technical problem solved by the present application is to provide a fishbone-Tesla valve micro mixing chip and its preparation method and application aiming at solving the problem of further improving the mixing efficiency of the Tesla micro mixing chip in the prior art.

[0007] The technical solution adopted by the present application to solve the technical problem is as follows:

[0008] A fishbone-Tesla valve micro mixing chip comprises a chip body, a Tesla valve and at least two mixing inlets, the Tesla valve comprises at least one mixing unit, the mixing inlets are in communication with the unit inlets of the outermost mixing units, wherein at least one mixing unit in the Tesla valve is provided with at least one fishbone structure, and the sharp corners of the fishbone structure face the mixing inlets.

[0009] The fishbone-Tesla valve micro mixing chip, wherein the mixing unit comprises:

[0010] a first gradually expanding channel having a unit inlet;

[0011] a second gradually expanding channel in communication with the side of the first gradually expanding channel;

[0012] a gradually tapering bend in communication with the outlet of the first gradually expanding channel and the side of the second gradually expanding channel;

[0013] wherein the end of the second gradually expanding channel away from the first gradually expanding channel is a unit outlet.

[0014] The fishbone-Tesla valve micro mixing chip, wherein the fishbone structure is arranged in the first gradually expanding channel, and the fishbone structure comprises at least one of an outward convex fishbone structure and an inward concave fishbone structure.

[0015] The fishbone-Tesla valve micro mixing chip, wherein the mixing unit comprises a first type of unit, a second type of unit, a third type of unit and a fourth type of unit; the first type of unit, the second type of unit, the third type of unit and the fourth type of unit are sequentially connected to form a repeating unit group;

[0016] The second gradually expanding channels of the first type of unit and the third type of unit are located on the same side of the second gradually expanding channel of the second type of unit, respectively.

[0017] The second gradually expanding channels of the second type of unit and the fourth type of unit are located on different sides of the second gradually expanding channel of the third type of unit, respectively.

[0018] The fishbone-Tesla valve micro-mixing chip, wherein the fishbone structure is located in the first diverging channel corresponding to the second diverging channel in the first type of unit or in the first diverging channel corresponding to the second diverging channel in the third type of unit.

[0019] The fishbone-Tesla valve micro-mixing chip, wherein the fishbone structure comprises:

[0020] a first branch part and a second branch part;

[0021] The first branch part and the second branch part are connected to form an acute angle.

[0022] The second branch part is located between the first branch part and the second diverging channel.

[0023] The length of the second branch part is less than the length of the first branch part.

[0024] The fishbone-Tesla valve micro-mixing chip, wherein the cross-sectional width of the Tesla valve is microns.

[0025] The Reynolds number of the fluid in the mixing inlet is 0-10000.

[0026] A preparation method of the fishbone-Tesla valve micro-mixing chip according to any one of the preceding items, comprising the steps of:

[0027] providing a cover plate;

[0028] preparing a layer structure; wherein the layer structure forms a Tesla valve and at least two mixing inlets, and the preparation method of the layer structure comprises at least one of photolithography, etching, hot pressing, molding, injection molding, laser burning, milling, and 3D printing;

[0029] connecting the layer structure and the cover plate to obtain the fishbone-Tesla valve micro-mixing chip.

[0030] The preparation method of the fishbone-Tesla valve micro-mixing chip, wherein the fishbone structure adopts an outward convex fishbone structure or an inward concave fishbone structure; and the preparation of the layer structure comprises:

[0031] after one-time spin coating of photoresist on a substrate and covering a first mask plate, performing one-time exposure and one-time development on the photoresist;

[0032] after twice spin coating of photoresist and covering a second mask plate, performing twice exposure and twice development on the photoresist to obtain a mold of the Tesla valve and the mixing inlet combination, and preparing a layer structure based on the mold of the Tesla valve and the mixing inlet combination; or

[0033] The fishbone structure includes: an outward convex fishbone structure and an inward concave fishbone structure; the preparation layer structure includes:

[0034] After the substrate is spin-coated with a photoresist and covered with a first mask, the photoresist is exposed and developed once;

[0035] After secondary spin coating of the photoresist and covering the second mask, the photoresist is subjected to secondary exposure and secondary development;

[0036] After the photoresist is spin-coated three times and covered with a third mask, the photoresist is exposed and developed three times to obtain a mold of a Tesla valve and a mixed inlet combination, and a layer structure is prepared based on the mold of the Tesla valve and the mixed inlet combination.

[0037] Application of the above-mentioned fishbone-Tesla valve micro-mixing chip in drug or liposome mixing and drug or liposome synthesis.

[0038] Beneficial effect: At least one fishbone structure is provided in the Tesla valve, and the sharp corner of the fishbone structure faces the mixing inlet. When the fluid in the Tesla valve flows through the fishbone structure, the fishbone structure disperses the fluid in the Tesla valve to both sides, promoting the lateral flow of the fluid, thereby improving the mixing efficiency of the micro-mixing chip. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Schematic diagram of the structure of the micro-hybrid chip of the fishbone-Tesla valve in an embodiment of the present invention.

[0040] Figure 2 Schematic diagram of the structure of the Tesla valve in an embodiment of the present invention.

[0041] Figure 3 Schematic diagram of the structure of four micro-hybrid chips in the embodiment of the present invention.

[0042] Figure 4 1 is a diagram showing the grid independence test results of the micro-hybrid chip in an embodiment of the present invention.

[0043] Figure 5 1 is a local mixing streamline diagram of three micro-hybrid chips in an embodiment of the present invention when Re=20.

[0044] Figure 6 1 is a local velocity cross-sectional diagram of three micro-hybrid chips at Re=20 in an embodiment of the present invention.

[0045] Figure 7 1 is a mixing streamline diagram of three micro-hybrid chips in an embodiment of the present invention when Re=20.

[0046] Figure 8 1 is a velocity cross-sectional diagram of three micro-hybrid chips in an embodiment of the present invention when Re=20.

[0047] Figure 9 is the mixing index diagram of four micro mixing chips in the embodiment of the present application.

[0048] Figure 10 is the mixing streamline diagram of four micro mixing chips in the embodiment of the present application under different Reynolds numbers.

[0049] Figure 11 is the schematic diagram of the cross-section interception position of the micro mixing chip in the embodiment of the present application.

[0050] Figure 12 is the concentration diagram of each interception position of four micro mixing chips in the embodiment of the present application under different Reynolds numbers.

[0051] Figure 13 is the performance analysis diagram of four micro mixing chips in the embodiment of the present application.

[0052] Figure 14 is the experimental result diagram of four micro mixing chips in the embodiment of the present application.

[0053] Explanation of reference signs:

[0054] 10, chip body; 11, Tesla valve; 111, first diverging channel; 112, second diverging channel; 113, converging bend; 12, mixing inlet; 13, first type unit; 14, second type unit; 15, third type unit; 16, fourth type unit; 20, fishbone structure; 21, outer convex fishbone structure; 22, inner concave fishbone structure. DETAILED DESCRIPTION

[0055] In order to make the purpose, technical scheme and advantages of the present application more clear and definite, the present application is further described in detail below with reference to the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application.

[0056] Please also refer to Figures 1-3 , some embodiments of the fishbone-Tesla valve micro mixing chip are provided.

[0057] As shown in Figures 1-2 , the fishbone-Tesla valve micro mixing chip of the present application comprises: a chip body 10, a Tesla valve 11 and at least two mixing inlets 12 are formed, the Tesla valve 11 comprises at least one mixing unit, the mixing inlets 12 are communicated with the unit inlets of the outermost mixing unit, at least one mixing unit in the Tesla valve 11 is provided with at least one fishbone structure 20, and the sharp corners of the fishbone structure 20 are directed towards the mixing inlets 12.

[0058] Specifically, the Tesla valve 11 and the mixing inlet 12 are formed in the interior of the chip body 10, the mixing unit has a unit inlet and a unit outlet, when the Tesla valve 11 has multiple mixing units, the multiple mixing units are connected in sequence, the unit outlet of the previous mixing unit is connected with the unit inlet of the next mixing unit, and the unit inlet of the outermost mixing unit is communicated with the mixing inlet 12. Different fluids flow into the unit inlet of the mixing unit from the corresponding mixing inlet 12, and then flow out of the unit outlet of the mixing unit, and then enter the next mixing unit, until passing through all the mixing units, and then flow out of the unit outlet of the last mixing unit, so as to complete the mixing of different fluids.

[0059] At least one fishbone structure 20 is arranged in the Tesla valve 11, and the sharp corners of the fishbone structure 20 are directed towards the mixing inlet 12. When the fluid in the Tesla valve 11 flows through the fishbone structure 20, the fishbone structure 20 disperses the fluid in the Tesla valve 11 to flow to both sides, promotes the lateral flow of the fluid, and thus improves the mixing efficiency of the micro-mixing chip.

[0060] The Tesla valve 11 is a hollow channel structure, and the fishbone structure 20 is arranged on the inner wall of the Tesla valve 11. When different fluids flow into the Tesla valve 11, they are located in different layer zones, and the fluid in the Tesla valve 11 flows in a laminar flow manner, and the fluids in different layer zones flow respectively and are not easily mixed quickly. The fishbone structure 20 can destroy the laminar flow of the fluid in the Tesla valve 11, and the fluid has more lateral flow, so that the fluids in different layer zones are mixed quickly, and the mixing efficiency is improved.

[0061] In a preferred implementation manner of the embodiment of the present application, as shown in Figures 1-2 the mixing unit comprises:

[0062] a first diverging channel 111 having a unit inlet;

[0063] a second diverging channel 112 communicated with a side of the first diverging channel 111;

[0064] a converging bend 113 communicated with an outlet of the first diverging channel 111 and a side of the second diverging channel 112;

[0065] wherein an end of the second diverging channel 112 away from the first diverging channel 111 is a unit outlet.

[0066] Specifically, the mixing unit divides the fluid flowed into the unit inlet into two parts, one part of the fluid flows into the first diverging channel 111, and the other part of the fluid flows into the second diverging channel 112. The fluid in the first diverging channel 111 flows into the converging elbow 113 and returns to the second diverging channel 112, and since the flowing direction of the fluid in the converging elbow 113 is opposite to the flowing direction of the fluid in the second diverging channel 112, the two parts of the fluid are mixed with each other. The diverging channels are beneficial to reduce the pressure and the flow rate of the fluid, the first diverging channel 111 is also beneficial to more fluid flowing into the converging elbow 113, which is beneficial to increase the pressure of the fluid in the converging elbow 113, and the second diverging channel 112 is also beneficial to reduce the possibility of the fluid returning. The converging elbow 113 is beneficial to increase the pressure and the flow rate of the fluid flowing out of the converging elbow 113, and is beneficial to improve the mixing efficiency of the two parts of the fluid.

[0067] In a preferred implementation of the embodiment of the present application, as shown in Figure 1 and Figure 3 , the fishbone structure 20 is arranged in the first diverging channel 111, and the fishbone structure 20 includes at least one of an outward convex fishbone structure 21 and an inward concave fishbone structure 22.

[0068] Specifically, the fishbone structure 20 is arranged in the first diverging channel 111, and the fishbone structure 20 can also be arranged in the converging elbow 113 and the second diverging channel 112. Since the fluid in the first diverging channel 111 is mainly in a laminar flow, arranging the fishbone structure 20 in the first diverging channel 111 is beneficial to the mixing of the fluid in the first diverging channel 111. Compared with the converging elbow 113, the first diverging channel 111 has a larger size, and it is more convenient to arrange the fishbone structure 20 in the first diverging channel 111. The second diverging channel 112 is the mixing area of the two parts of the fluid, and compared with the second diverging channel 112, the improvement of the mixing efficiency is more significant when the fishbone structure 20 is arranged in the first diverging channel 111.

[0069] The fishbone structure 20 can be the outward convex fishbone structure 21 or the inward concave fishbone structure 22, the outward convex fishbone structure 21 increases the cross-sectional size of the channel structure, and the inward concave fishbone structure 22 reduces the cross-sectional size of the channel structure. The two kinds of fishbone structures 20 can be used alone or in combination.

[0070] In a preferred implementation of the embodiment of the present application, as shown in Figure 1 and Figure 3 , the fishbone structure 20 is arranged in the first diverging channel 111 corresponding to the position of the second diverging channel 112.

[0071] Specifically, since the fluid in the first diverging channel 111 adopts the flow mode of laminar flow, the flow division of the second diverging channel 112 is to divide the fluid in the partial laminar region, and the two parts of the divided fluid are respectively limited in the first diverging channel 111 and the second diverging channel 112, therefore, it is necessary to mix the undivided fluid by the fishbone structure 20 before the division, which is more conducive to improving the mixing efficiency.

[0072] In a preferred implementation form of the embodiment of the application, as shown in Figure 1 and Figure 3 the mixing unit comprises: a first type unit 13, a second type unit 14, a third type unit 15 and a fourth type unit 16; the first type unit 13, the second type unit 14, the third type unit 15 and the fourth type unit 16 are sequentially connected to form a repeating unit group; the second diverging channel 112 of the first type unit 13 and the second diverging channel 112 of the third type unit 15 are respectively located on the same side of the second diverging channel 112 of the second type unit 14; the second diverging channel 112 of the second type unit 14 and the second diverging channel 112 of the fourth type unit 16 are respectively located on different sides of the second diverging channel 112 of the third type unit 15.

[0073] Specifically, the mixing unit has four types, which are the first type unit 13, the second type unit 14, the third type unit 15 and the fourth type unit 16. The four types of mixing units are sequentially connected to form a repeating unit group, and the repeating unit groups can be connected to form the entire Tesla valve 11. The structure of each repeating unit group is the same, and can be repeatedly arranged and connected. The directions and positions of the four types of mixing units in a single repeating unit group are different.

[0074] With reference to the second diverging channel 112, the four types of mixing units are distinguished. The second diverging channel 112 of the first type unit 13, the second diverging channel 112 of the second type unit 14 and the second diverging channel 112 of the third type unit 15 form a trapezoid, so that the second diverging channel 112 of the first type unit 13 and the second diverging channel 112 of the third type unit 15 are located on the same side of the second diverging channel 112 of the second type unit 14. The second diverging channel 112 of the second type unit 14, the second diverging channel 112 of the third type unit 15 and the second diverging channel 112 of the fourth type unit 16 form a step shape, so that the second diverging channel 112 of the second type unit 14 and the second diverging channel 112 of the fourth type unit 16 are located on both sides of the second diverging channel 112 of the third type unit 15. Of course, the number of mixing units in a single repeating unit group can be increased, and the directions and positions of the mixing units can be adjusted.

[0075] In a preferred implementation form of the embodiment of the application, as shown inFigure 1 and Figure 3 As shown in FIG. 1 and FIG. 2, the fishbone structure 20 is located in the first diverging channel 111 of the first type unit 13 corresponding to the second diverging channel 112, or is located in the first diverging channel 111 of the third type unit 15 corresponding to the second diverging channel 112.

[0076] Specifically, there is at least one fishbone structure 20 in each repeating unit group, and the fishbone structure 20 can be arranged in the mixing unit or not. For example, in a single repeating unit group, the first type unit 13 and the third type unit 15 are arranged with the fishbone structure 20, and the second type unit 14 and the fourth type unit 16 are not arranged with the fishbone structure 20. Since the extension direction of the first diverging channel 111 of the first type unit 13 and the extension direction of the first diverging channel 111 of the third type unit 15 are consistent with the length direction of the Tesla valve 11, and the extension direction of the first diverging channel 111 of the second type unit 14 and the extension direction of the first diverging channel 111 of the fourth type unit 16 are not consistent with the length direction of the Tesla valve 11, arranging the fishbone structure 20 in the first type unit 13 and the third type unit 15 is more conducive to improving the mixing efficiency.

[0077] In a preferred implementation manner of the embodiment of the present application, as shown in FIG. 1 and FIG. 2, the fishbone structure 20 comprises: Figure 1 and Figure 2 As shown in FIG. 1 and FIG. 2, the fishbone structure 20 comprises:

[0078] a first branch part and a second branch part;

[0079] Wherein, the first branch part and the second branch part are connected to form a sharp angle; the second branch part is located between the first branch part and the second diverging channel 112; the length of the second branch part is less than the length of the first branch part.

[0080] Specifically, the fishbone structure 20 is V-shaped, the first branch part and the second branch part are connected to form the V-shaped fishbone structure 20, and the connection of the first branch part and the second branch part forms the sharp angle of the fishbone structure 20. The length of the first branch part is longer, and the length of the second branch part is shorter. The first branch part is away from the second diverging channel 112, and the second branch part is close to the second diverging channel 112, so that the sharp angle of the fishbone structure 20 is closer to the second diverging channel 112, which is more conducive to disturbing and mixing the fluid before the fluid is divided into the second diverging channel 112.

[0081] In a preferred implementation manner of the embodiment of the present application, the cross-sectional width of the Tesla valve 11 is microns; and the Reynolds number of the fluid of the mixing inlet 12 is 0-10000.

[0082] Specifically, the cross-sectional width of the Tesla valve 11 is micron level, forming a micron-level Tesla valve 11, and a micron-level micro-mixing chip is obtained. The cross-sectional size of the fishbone structure 20 is micron level, and the cross-sectional size of the fishbone structure 20 is smaller than the cross-sectional size of the Tesla valve 11. The fishbone-Tesla valve micro-mixing chip of the application has a large mixing efficiency improvement effect in the application scene of low Reynolds number.

[0083] Based on the fishbone-Tesla valve micro-mixing chip of any one of the above embodiments, the application further provides a preferred embodiment of a preparation method of a fishbone-Tesla valve micro-mixing chip.

[0084] The preparation method of the fishbone-Tesla valve micro-mixing chip of the embodiment of the application comprises the following steps:

[0085] Step S100, providing a cover plate;

[0086] Step S200, preparing a layer structure; wherein the layer structure forms a Tesla valve and at least two mixing inlets, and the preparation method of the layer structure comprises at least one of photolithography, etching, hot pressing, molding, injection molding, laser burning, milling, and 3D printing;

[0087] Step S300, connecting the layer structure and the cover plate to obtain a fishbone-Tesla valve micro-mixing chip.

[0088] Specifically, the materials for manufacturing the micro-mixing chip mainly include metal materials, inorganic materials, polymer materials, and paper. The inorganic materials include silicon, glass, and ceramics. The polymer materials include elastomer materials, thermosetting materials, thermoplastic materials, and hydrogels. The metal materials are selected from stainless steel, nickel, etc. The elastomer materials are selected from polydimethylsiloxane (PDMS), etc. The thermosetting materials are selected from polyester (TPE), etc. The thermoplastic materials are selected from polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene glycol diacrylate (PEGDA), perfluorinated compounds (PFEP / PFA / PFPE), and polyurethane (PU). The glass material has excellent chemical stability and optical transparency, and is often used in high-precision or chemically inert applications. The three-dimensional structure produced has high surface finish. The metal material is suitable for applications requiring high temperature resistance or high strength. The metal mold can be made by electroforming, or the fine microstructure can be directly machined by micro-milling.

[0089] Photolithography is a process of patterning on a substrate such as silicon, glass, etc. using light imaging and photosensitive glue. The basic process includes pretreatment, glue coating, pre-baking, exposure, development, and hardening. Soft lithography can be used to cover the PDMS mold to form a three-dimensional structure, which is suitable for rapid prototyping. Molding method first makes a positive mold (the protruding part of the required channel), then pours the liquid polymer material, and then peels off the cured polymer material and the positive mold to obtain a chip with microchannels. Hot pressing method is suitable for mass production by heating plastic sheet and pressing into the mold to form microchannels. 3D printing technology based on photosensitive resin or metal powder can also manufacture complex three-dimensional structures with high flexibility. Different materials require different preparation methods, and the materials and preparation methods can be selected according to the needs.

[0090] For example, the micro-mixing chip can be prepared by molding method, first preparing a mold, then manufacturing a layer structure based on the mold, connecting the layer structure and the cover plate to obtain the micro-mixing chip. The shape of the Tesla valve and the mixing inlet is related to the shape of the mold.

[0091] If the fishbone structures are all convex or all concave, the fishbone structure is simpler and the preparation steps of the mold are less. Step S200 specifically includes:

[0092] Step S211, after one-time spin coating of photoresist on the substrate and covering the first mask plate, the photoresist is exposed and developed once.

[0093] Step S212, after twice spin coating of photoresist and covering the second mask plate, the photoresist is exposed and developed twice to obtain a mold of a Tesla valve and a mixing inlet combination, and a layer structure is prepared based on the mold of the Tesla valve and the mixing inlet combination.

[0094] Specifically, the Tesla valve and the mixing inlet combination with fishbone structures can be divided into two parts, one part does not contain fishbone structures, and the other part contains fishbone structures. Therefore, the mold can also be divided into two parts, one part of the mold contains fishbone structures, and the other part of the mold does not contain fishbone structures. When preparing the mold, first prepare the part without fishbone structures, and then prepare the part with fishbone structures.

[0095] After one-time spin coating of photoresist on the substrate, first exposure is performed using the first mask plate, and after removing the first mask plate, first development is performed to obtain the part without fishbone structures. Then, after twice spin coating of photoresist, second exposure is performed using the second mask plate, and after removing the second mask plate, second development is performed to form the part with fishbone structures on the part without fishbone structures, and the remaining photoresist is cured to obtain a mold of a Tesla valve and a mixing inlet combination.

[0096] The fishbone structure includes an outward convex fishbone structure and an inward concave fishbone structure, so that the fishbone structure is more complex and the preparation steps of the mold are more.

[0097] Step S221: after once spin-coating photoresist on the substrate and covering the first mask plate, the photoresist is exposed and developed once;

[0098] Step S222: after twice spin-coating photoresist and covering the second mask plate, the photoresist is exposed and developed twice;

[0099] Step S223: after three times of spin-coating photoresist and covering the third mask plate, the photoresist is exposed and developed three times to obtain the mold of the Tesla valve and the mixed inlet combination, and based on the mold of the Tesla valve and the mixed inlet combination, the layer structure is prepared.

[0100] Specifically, the Tesla valve and the mixed inlet combination carrying the fishbone structure can be divided into three parts, the first part does not contain the fishbone structure, the second part contains the inward concave fishbone structure, and the third part contains the outward convex fishbone structure, so that the mold can also be divided into three parts, the first part of the mold does not contain the fishbone structure, the second part of the mold contains the inward concave fishbone structure, and the third part of the mold contains the outward convex fishbone structure. When preparing the mold, first, the part without the fishbone structure is prepared, then the part with the inward concave fishbone structure is prepared, and finally, the part with the outward convex fishbone structure is prepared.

[0101] After once spin-coating photoresist on the substrate, the first mask plate is used for once exposure, and after removing the first mask plate, the photoresist is developed once to obtain the part without the fishbone structure. Then, after twice spin-coating photoresist, the second mask plate is used for twice exposure, and after removing the second mask plate, the photoresist is developed twice to form the part with the inward concave fishbone structure on the part without the fishbone structure. Then, after three times of spin-coating photoresist, the third mask plate is used for three times of exposure, and after removing the third mask plate, the photoresist is developed three times to form the part with the outward convex fishbone structure on the part with the inward concave fishbone structure, and the remaining photoresist is cured to obtain the mold of the Tesla valve and the mixed inlet combination.

[0102] In order to improve the mixing performance of the Tesla micro-mixing chip, different fishbone structures are added above the flow channel to enhance the lateral flow of the fluid and form a spiral flow. Figure 3A Tesla micromixing chip (TMSHS) with a concave fishbone structure and a Tesla micromixing chip (TMRHS) with a convex fishbone structure were designed. Numerical simulations were used to analyze the effects of different fishbone structures on fluid flow trajectory and mixing. A T-shaped micromixing chip (T-mixer) and a Tesla micromixing chip (TM) were used as control examples. The T-shaped micromixing chip does not contain a Tesla valve or fishbone structure, while the Tesla micromixing chip contains a Tesla valve but no fishbone structure. The performance of the four micromixing chips, T-mixer, TM, TMSHS, and TMRHS, was evaluated over a wide Reynolds number range (Re = 0.2-100). The micromixing chips were then fabricated using soft lithography, and the simulation results were verified by experimental results, demonstrating that the fishbone structure significantly enhances mixing.

[0103] Figure 3 Schematic diagrams of the structures of four micro-mixing chips are shown. The width of the mixing inlet and mixing outlet of the micro-mixing chip is denoted by w, which is 200 μm. The length of the mixing inlet and mixing outlet is denoted by W, which is 500 μm. The total channel length L is 8 mm. The height and width of the inlet of the second gradually diverging channel are denoted by a, which is 150 μm. The outlet of the tapered channel is denoted by b, which is 100 μm. The depth of the concave fishbone structure in the TMSHS and the height of the convex fishbone structure in the TMRHS are denoted by c, which is 50 μm. The width of the fishbone structure is denoted by e, which is 65 μm. The spacing d between adjacent fishbone structures is 60 μm. The opening angle θ of the fishbone structure is 120°.

[0104] Table 1 Parameters of micro-hybrid chip

[0105]

[0106] The numerical simulation of the micro-hybrid chip was performed using COMSOL Mutiphysics software. It was assumed that the fluid flow was incompressible laminar flow and the fluid flow process was controlled by equations (1)-(3):

[0107] Continuity equation:

[0108]

[0109] Where, Represents the velocity vector, m / s.

[0110] Navier-Stokes equations:

[0111]

[0112] Where ρ represents density, kg / m 3 ; p represents pressure, MPa; μ represents dynamic viscosity, Pa·s.

[0113] The convection-diffusion equation is:

[0114]

[0115] where c represents concentration, mol / m 3 ; D represents molecular diffusivity, m 2 / s.

[0116] The density and dynamic viscosity of the fluid used in the study are 0.998 x 10 -3 kg / m 3 and 1.002 x 10 -3 Pa-s, respectively, and the molecular diffusivity is taken as that of the ink, which is 3.23 x 10 -10 m 2 / s. The inlet is a velocity inlet, and the fluid concentrations in the two mixing inlets are 1 mol / m 3 and 0 mol / m 3 , respectively. The outlet is a pressure outlet with a static pressure of 0 MPa.

[0117] The Reynolds number (Re) is used to characterize the fluid flow condition:

[0118]

[0119] where V represents the flow velocity, m / s; and d represents the hydraulic diameter, m.

[0120] The mixing performance of the micro-mixing chip is demonstrated by the mixing index (MI):

[0121]

[0122] where σ represents the standard deviation of the outlet concentration, mol / m 3 ; c i represents the concentration at each sampling point, mol / m 3 ; represents the concentration of idealized uniform mixing, mol / m 3 .

[0123] The range of MI is from 0 (σ = σ max = 0.5) to 1 (σ = 1). The pressure drop (Δp) is the pressure difference before and after the fluid flows in the flow channel, i.e.:

[0124] Δp = p1 - p2 (8)

[0125] where p1 represents the pressure at the inlet of the main channel, MPa; and p2 represents the pressure at the outlet, MPa.

[0126] Mesh independence test. Since the numerical simulation results are affected by the mesh division, the mesh independence of the model needs to be verified. The TM model was tested at Re = 10 with the number of meshes from 536775 to 7220161. Figure 4 The outlet cross-sectional concentration distribution under different number of meshes was shown. When the number of meshes was from 5932360 to 7220161, the curve shape almost did not change. The curve shape of the number of meshes of 4459551 was also very close to the curve of the number of meshes of 7220161. The more the number of model meshes, the longer the calculation time. In order to ensure the accuracy of the calculation results and improve the calculation efficiency, the mesh division scheme of the number of meshes of 445955 was selected as the mesh division scheme of the four kinds of micro mixing chips.

[0127] The influence of fishbone structure on mixing. Figure 5 and Figure 7 The concentration streamline changes of the three kinds of micro mixing chips at Re = 20 were shown. It can be seen that the fishbone structure in TMSHS and TMRHS disperses the fluid near the middle of the channel to both sides of the flow channel, promoting the lateral flow of the fluid. In addition, the concave fishbone structure of TMSHS strengthens the lateral flow of the fluid in the part curved Tesla structure sub-channel, which is also one of the reasons why the overall concentration streamline in TMSHS is quite different from the other two kinds of micro mixing chips.

[0128] Figure 6 and Figure 8 The size of the velocity of part cross-section in the micro mixing chip at Re = 20 was shown, in which the velocity of the cross-section of TMSHS was the largest. The concave fishbone structure obviously changed the velocity distribution in the flow channel. The flow velocity in the convex fishbone was lower than that in the main channel, and did not affect the velocity distribution in the main channel.

[0129] Figure 9 and Figure 10 The MI changes of the four kinds of micro mixing chips with the mixing distance at different Re were shown. When Re was low, the mixing mainly relied on the molecular diffusion to complete. For example, Figure 9 (a), (b) and Figure 10 (a), (b) of the four kinds of micro mixing chips, the MI change curves with the mixing distance were similar. With the increase of Re, such as Figure 9 (c), (d) and Figure 10 (c), (d) of the three kinds of micro mixing chips with Tesla structure, the MI increased rapidly. The MI of T-mixer did not change obviously. This is because the Tesla structure makes the fluid form chaotic convection, which promotes mixing. The MI of TMSHS and TMRHS is higher than that of TM, because the fishbone structure increases the contact area between fluids of different concentrations. For example, Figure 9 (d) and Figure 10(d), the MI of TMSHS rises faster than TM and TMRHS in the first 2 mm mixing length, which is due to the stronger chaotic advection caused by the concave fishbone structure. The gap between TM and TMRHS is narrowing, which shows that the effect of convex fishbone structure on mixing is less as the flow rate is higher.

[0130] Figure 11 and Figure 12 The concentration distribution of two cross sections of the micro mixing chip at different Re is shown, and the cross sections of TMSHS and TMRHS are taken at the same position as TM. With the increase of Re, the transverse flow of fluid in the channel is enhanced, and chaotic advection is generated. Cross sections A1-A1 and A2-A2 are both at the junction of the two sub-channels of the Tesla structure. Although the cross section A1-A1 of TMSHS and TMRHS is not close to the fishbone structure, the cross section concentration distribution is different from TM, and the area of high concentration fluid wrapped by low concentration fluid on the side with fishbone structure is larger, which is caused by the transverse flow caused by the fishbone structure. With the increase of Re, vortex gradually forms in the main channel of TMSHS at cross section A2-A2, while TMRHS only forms weak vortex at the fishbone structure. Due to the stronger effect of concave fishbone structure on fluid, the transverse flow of fluid in the main channel of TMSHS is different from TM and TMRHS, and stronger chaotic advection is generated, so that TMSHS has a stronger promoting effect on fluid mixing.

[0131] Figure 13 (a) shows the relationship between the MI of the micro mixing chip outlet and Re. When Re = 0.2-5, the mixing in the micro mixing chip mainly relies on molecular diffusion. With the gradual increase of fluid flow rate, the contact time between fluids of different concentrations becomes shorter, so the MI gradually decreases. When Re > 5, due to the acceleration of fluid flow rate, chaotic advection generated by Tesla structure gradually plays a leading role in mixing, so their MI gradually rises. When Re > 60, the MI of TM, TMSHS and TMRHS is greater than 90%. Finally, at Re = 100, the MI of the outlets of the three Tesla micro mixing chips is basically the same. Among them, when Re = 1-30, the fishbone structure has the best effect on enhancing mixing. In order to judge the promotion effect of fishbone structure on the MI of TM, the MI promotion efficiency (η) is introduced.

[0132]

[0133] In the formula, MI HS represents the MI of the micro mixing chip with fishbone structure outlet; MI TM represents the MI of TM outlet.

[0134] Figure 13(b) shows the promotion efficiency of different fishbone structures on TM mixing index. With the increase of Re, the η of TMSHS and TMRHS first increases and then decreases, and when Re = 5, the η of both is the highest, which is 65% and 34% respectively. That is, the fishbone structure can significantly promote the mixing when the mixing ability of the micro-mixing chip is the worst. Figure 13 (c) shows the relationship between △P and Re of four micro-mixing chips. With the increase of Re, the resistance of fluid flow in the mixer is also greater. Among them, TMSHS has the largest △P due to the concave fishbone structure which has the largest resistance to fluid. Although the convex fishbone structure of TMRHS changes the flow path of the fluid, it also increases the cross-sectional area of the channel, so the △P is basically the same as TM. In addition, in order to investigate the energy consumption of different micro-mixing chips, the mixing parameter (MP) is introduced:

[0135]

[0136] As Figure 13 (d), with the increase of Re, the value of MP is constantly declining, and the MP of TM, TMSHS and TMRHS all exceeds T-mixer from Re = 10. Among them, the MP of TMRHS is the highest among the three, that is, under the same energy consumption, the mixing effect of TMRHS is the best.

[0137] In order to verify the mixing performance of the micro-mixing chip, NaOH solution and phenolphthalein solution are used for mixing reaction experiment. The photos of solution mixing are taken by stereomicroscope. The mixing performance of the micro-mixing chip is judged by the uniformity of the pink formed by the reaction of the two solutions. The more uniform the pink distribution, the better the mixing effect. Figure 14 (a) shows the mixing effect of micro-mixing chip when Re = 60. The mixing effect of TMSHS and TMRHS is obviously better than that of TM. In the front end of the mixer, the enhancement of the fishbone structure of TMSHS and TMRHS on the mixing effect can be obviously seen. The fishbone structure changes the flow direction of part of the solution, so that the contact area of the two solutions increases, thereby improving the reaction degree of the solution. In the middle part of the micro-mixing chip, it can be seen that the reaction degree of the solution in TMSHS is obviously better than that in TMRHS and TM, which is consistent with the result shown in Figure 9 (d). The MI is calculated by measuring the gray value at the outlet of the micro-mixing chip, Figure 14 (b) shows the relationship between the outlet MI of different micro-mixing chips and Re. The trend of the change of mixing index with the increase of Re is the same as that in simulation. However, due to the influence of the manufacturing accuracy of the micro-mixing chip and the different diffusion coefficients of the solution, there is a certain difference between the experimental results and the simulation.

[0138] The fishbone structure enhances the lateral flow of fluid while generating vortex flow in the channel. The concave fishbone structure can increase the fluid flow rate, the disturbance to the fluid is the strongest, and has the best mixing effect. However, it has the largest pressure drop due to the largest disturbance to the fluid. The TMRHS has better energy efficiency because it ensures the disturbance to the fluid while expanding the channel cross section. When Re>60, the MI of TM, TMSHS and TMRSH are all greater than 90%. The fishbone structure significantly improves the mixing performance when Re=0.2-30, which can make up for the low MI of the Tesla micro mixing chip at low Re. When Re=5, the η of TMSHS and TMRHS is the highest, which is 65% and 34% respectively. When Re>30, the influence of the fishbone structure on the mixing result gradually weakens, but the concave fishbone structure can still quickly improve the MI at the initial stage of mixing. In addition, the mixing experiment results of phenolphthalein solution and NaOH solution confirm the simulation results. This study has guiding significance for improving the mixing performance of the micro mixing chip in a wide range of Reynolds numbers (Re=0-100), and in the future, the shape and number of the fishbone structure will be optimized to further improve the mixing performance of the micro mixing chip.

[0139] The fishbone-Tesla valve micro mixing chip of the present application can be applied to drug or liposome mixing, drug or liposome synthesis. Especially for nanodrugs and nanoliposomes, when mixing or synthesizing nanodrugs, mixing or synthesizing nanoliposomes, the fishbone-Tesla valve micro mixing chip of the present application greatly improves the lateral flow of fluid by combining fishbone structure and Tesla valve, realizes high mixing efficiency, and can be applied to the mixing or synthesis of nanodrugs and nanoliposomes. Liposomes as drug carriers have the functions of slow-release of drugs and reduction of drug toxicity, and can also improve the stability and targeting of drugs.

[0140] Liposomes are closed vesicles formed by phospholipids dispersed in water, and the phospholipids are selected from glycerophospholipids or sphingomyelin. The glycerophospholipids include at least one of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and cardiolipin. The sphingomyelin includes at least one of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and diphosphatidylglycerol.

[0141] For example, different chain length phosphatidylcholine (PC), cholesterol and dicetyl phosphate (DCP) are used as components for preparing liposomes. The phosphatidylcholine can be dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, dilauryl phosphatidylcholine, etc.

[0142] It should be understood that the application of the present application is not limited to the above examples, and those skilled in the art can make improvements or changes according to the above description, and all these improvements and changes shall belong to the protection scope of the appended claims of the present application.

Claims

1. A fishbone-Tesla valve micro-mixing chip comprising: The chip body forms a Tesla valve and at least two mixing inlets, the Tesla valve comprises at least one mixing unit, the mixing inlets are communicated with the unit inlets of the outermost mixing units, characterized in that at least one mixing unit in the Tesla valve is provided with at least one herringbone structure, and the sharp corners of the herringbone structure are directed towards the mixing inlets. The mixing unit comprises: A first diverging channel having a unit inlet; A second diverging channel communicated with the side of the first diverging channel; A converging bend communicated with the outlet of the first diverging channel and the side of the second diverging channel; Wherein, one end of the second diverging channel away from the first diverging channel is a unit outlet; The herringbone structure is arranged in the first diverging channel, and the herringbone structure comprises at least one of an outward convex herringbone structure and an inward concave herringbone structure; The herringbone structure comprises: A first branch part and a second branch part; Wherein, the first branch part and the second branch part are connected to form a sharp corner; The second branch part is located between the first branch part and the second diverging channel; The length of the second branch part is less than the length of the first branch part; The cross-sectional width of the Tesla valve is microns; The Reynolds number of the fluid in the mixing inlet is 0.2-60.

2. The fishbone-Tesla valve micro-mixing chip according to claim 1, wherein, The mixing unit comprises a first type of unit, a second type of unit, a third type of unit and a fourth type of unit; the first type of unit, the second type of unit, the third type of unit and the fourth type of unit are sequentially connected to form a repeating unit group; The second diverging channel of the first type of unit and the second diverging channel of the third type of unit are located on the same side of the second diverging channel of the second type of unit; The second diverging channel of the second type of unit and the second diverging channel of the fourth type of unit are located on different sides of the second diverging channel of the third type of unit.

3. The fishbone-Tesla valve micro-mixing chip of claim 2, wherein, The herringbone structure is located in the first type of unit in the first diverging channel corresponding to the position of the second diverging channel, or in the third type of unit in the first diverging channel corresponding to the position of the second diverging channel.

4. A method of fabricating a fishbone-Tesla valve micro-mixer chip according to any one of claims 1 to 3, characterized by, The method comprises the steps of: Providing a cover plate; Preparing a layer structure; wherein the layer structure forms a Tesla valve and at least two mixing inlets, and the preparation method of the layer structure comprises at least one of photolithography, etching, hot pressing, molding, injection molding, laser burning, milling and 3D printing; Connecting the layer structure and the cover plate to obtain a herringbone-Tesla valve micro-mixing chip.

5. The method for preparing a micro-hybrid chip of a fishbone-Tesla valve according to claim 4, characterized in that: The herringbone structures all adopt outward convex herringbone structures, or all adopt inward concave herringbone structures; the preparation of the layer structure comprises: After one-time spin coating of photoresist on the substrate and covering the first mask plate, the photoresist is exposed and developed once; After twice spin coating of photoresist and covering the second mask plate, the photoresist is exposed and developed twice to obtain a mold of the Tesla valve and the mixing inlet combination, and based on the mold of the Tesla valve and the mixing inlet combination, the layer structure is prepared; or The herringbone structure comprises an outward convex herringbone structure and an inward concave herringbone structure; the preparation of the layer structure comprises: exposing and developing the photoresist once after spin-coating the photoresist on the substrate and covering the first mask plate; exposing and developing the photoresist twice after spin-coating the photoresist twice and covering the second mask plate; exposing and developing the photoresist thrice after spin-coating the photoresist thrice and covering the third mask plate, to obtain a mold of the Tesla valve and the mixed inlet combination, and based on the mold of the Tesla valve and the mixed inlet combination, to prepare a layer structure.

6. The application of the fishbone-Tesla valve micro-mixing chip according to any one of claims 1-3 to drug or liposome mixing or drug or liposome synthesis.

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