Micro-mixing chip of fishbone-Tesla valve as well as preparation method and application of micro-mixing chip

Abstract

The invention 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 are formed, the Tesla valve comprises at least one mixing unit, the mixing inlets are communicated with the unit inlets of the mixing units on the outermost side, and the mixing units are communicated with the mixing inlets of the mixing units on the outermost side; at least one mixing unit in the Tesla valve is provided with at least one fishbone structure, and the sharp corner of the fishbone structure faces the mixing inlet. At least one fishbone structure is arranged in the Tesla valve, the sharp corner of the fishbone structure faces the mixing inlet, when fluid in the Tesla valve flows through the fishbone structure, the fluid in the Tesla valve dispersedly flows towards the two sides through the fishbone structure, transverse flowing of the fluid is promoted, and therefore the mixing efficiency of the micro mixing chip is improved.

Description

Technical Field

[0001] The present invention relates to the field of micro-mixing technology, and in particular to a micro-mixing chip of a herringbone-Tesla valve and a preparation method thereof. Background Art

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

[0003] Due to the limitations of micrometer or nanometer scale, the fluid in the micro-mixing chip flows in a laminar flow, 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 one after another. At present, micro-mixing chips are divided into active and passive micro-mixing chips according to whether they require external energy input. Active micro-mixing chips require external energy input, including electric, magnetic, acoustic, thermal and pressure, to improve the mixing efficiency. Although active micro-mixing chips have more precise control over fluids, their structures are complex, and the introduced energy fields have additional effects on the flow state of the fluid. Passive micro-mixing chips use specially structured flow channels to mix different types of fluids, and have been widely studied due to their low cost, easy integration, and no need for external energy input. According to different mixing principles, passive micro-mixing chips are divided into micro-mixing chips that rely on Dean vortex mixing, micro-mixing chips that mix based on contraction and expansion effects, micro-mixing chips with splitting and recombination (SAR) structures, and micro-mixing chips that rely on spiral flow mixing. The mixing mechanism includes the introduction of lamination in the channel and the formation of chaotic advection.

[0004] Tesla micro-hybrid chip is a micro-hybrid 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 mixing is promoted by the lateral flow and chaotic convection generated by the collision between the fluids. In the prior art, the shape and structure optimization design is performed by using genetic algorithms, and better performance than the prototype Tesla micro-hybrid chip is obtained. However, the mixing efficiency of the Tesla micro-hybrid chip in the prior art still needs to be further improved.

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

[0006] The technical problem to be solved by the present invention is that, in view of the above-mentioned defects of the prior art, a micro-mixing chip of a herringbone-Tesla valve and a preparation method and application thereof are provided, aiming to solve the problem that the mixing efficiency of the Tesla micro-mixing chip in the prior art still needs to be further improved.

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

[0008] A micro-mixing chip of a herringbone-Tesla valve comprises: a chip body, forming a Tesla valve and at least two mixing inlets, wherein the Tesla valve comprises at least one mixing unit, and the mixing inlet is connected to the unit inlet of the outermost mixing unit, wherein at least one mixing unit in the Tesla valve is provided with at least one herringbone structure, and the sharp corner of the herringbone structure faces the mixing inlet.

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

[0010] a first diverging channel having a cell inlet;

[0011] a second gradually diverging channel, communicating with a side portion of the first gradually diverging channel;

[0012] a gradually contracting bend communicating with the outlet of the first gradually expanding channel and the side of the second gradually expanding channel;

[0013] Wherein, an end of the second gradually diverging channel away from the first gradually diverging channel is a unit outlet.

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

[0015] The micro-mixing chip of the herringbone-Tesla valve, 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 diverging channel of the first type of unit and the second gradually diverging channel of the third type of unit are respectively located on the same side of the second gradually diverging channel of the second type of unit;

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

[0018] The micro-hybrid chip of the herringbone-Tesla valve, wherein the herringbone structure is located at a position corresponding to the second gradually expanding channel in the first gradually expanding channel of the first type unit, or is located at a position corresponding to the second gradually expanding channel in the first gradually expanding channel of the third type unit.

[0019] The micro-hybrid chip of the herringbone-Tesla valve, wherein the herringbone structure comprises:

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

[0021] Wherein, the first branch portion and the second branch portion are connected to form a sharp angle;

[0022] The second branch portion is located between the first branch portion and the second gradually expanding channel;

[0023] The length of the second branch portion is smaller than the length of the first branch portion.

[0024] The micro-hybrid chip of the herringbone-Tesla valve, wherein the cross-sectional width of the Tesla valve is in the micrometer range;

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

[0026] A method for preparing a micro-hybrid chip of a herringbone-Tesla valve as described in any one of the above, comprising the steps of:

[0027] Provide cover plate;

[0028] Prepare 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 includes: at least one of photolithography, etching, hot pressing, molding, injection molding, laser ablation, milling, and 3D printing;

[0029] The layer structure and the cover plate are connected to obtain a micro-hybrid chip of a herringbone-Tesla valve.

[0030] The method for preparing the micro-hybrid chip of the fishbone-Tesla valve, wherein the fishbone structures all adopt an outward convex fishbone structure, or all adopt an inward concave fishbone structure; the preparation layer structure comprises:

[0031] After the substrate is spin-coated with photoresist once and covered with a first mask, the photoresist is exposed and developed once;

[0032] After secondary spin coating of photoresist and covering the second mask, secondary exposure and secondary development are performed on the photoresist 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; or

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

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

[0035] After the photoresist is spin-coated for the second time and covered with a second mask, the photoresist is subjected to secondary exposure and secondary development;

[0036] After the photoresist is spin-coated three times and covered with the 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] A micro-mixing chip with a fishbone-Tesla valve as described above is used 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, promotes the lateral flow of the fluid, and thus improves 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 herringbone-Tesla valve in an embodiment of the present invention.

[0040] Figure 2 Schematic diagram of the structure of the Tesla valve in the 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 graph 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-mixing chips in the embodiment of the present invention when Re=20.

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

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

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

[0047] Fig. 9 Graphs showing mixing indices of four micro-mixing chips in an embodiment of the present invention.

[0048] Fig.10 1 is a mixing streamline diagram of four micro-mixing chips under different Reynolds numbers in an embodiment of the present invention.

[0049] Fig.11 Schematic diagram of the cross-section position of the micro-hybrid chip in the embodiment of the present invention.

[0050] Fig.12 1 is a concentration diagram of four micro-mixing chips at different Reynolds numbers at each interception position in the embodiment of the present invention.

[0051] Fig.13 1 is a performance analysis diagram of four micro-hybrid chips in an embodiment of the present invention.

[0052] Fig.14 Graphs showing the experimental results of four micro-hybrid chips in the embodiments of the present invention.

[0053] Description of reference numerals:

[0054] 10. Chip body; 11. Tesla valve; 111. First gradually expanding channel; 112. Second gradually expanding channel; 113. Gradually contracting bend; 12. Mixing inlet; 13. First type of unit; 14. Second type of unit; 15. Third type of unit; 16. Fourth type of unit; 20. Fishbone structure; 21. Outward convex fishbone structure; 22. Inward concave fishbone structure. DETAILED DESCRIPTION

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

[0056] Please also see Figure 1-Figure 3 The present invention provides some embodiments of a micro-hybrid chip of a herringbone-Tesla valve.

[0057] like Figure 1-Figure 2 As shown, the micro-mixing chip of the herringbone-Tesla valve of the present invention includes: a chip body 10, forming a Tesla valve 11 and at least two mixing inlets 12, the Tesla valve 11 includes at least one mixing unit, the mixing inlet 12 is connected to the unit inlet of the outermost mixing unit, at least one mixing unit in the Tesla valve 11 is provided with at least one herringbone structure 20, and the sharp corner of the herringbone structure 20 faces the mixing inlet 12.

[0058] Specifically, the Tesla valve 11 and the mixing inlet 12 are formed inside 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, and the unit outlet of the previous mixing unit is connected to the unit inlet of the next mixing unit, and the unit inlet of the outermost mixing unit is connected to the mixing inlet 12. Different fluids flow into the unit inlet of the mixing unit from the corresponding mixing inlet 12, and flow out from the unit outlet of the mixing unit, and then enter the next mixing unit, until passing through all mixing units and flowing out from 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 provided in the Tesla valve 11, and the sharp corner of the fishbone structure 20 faces 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 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 layers, and the fluid in the Tesla valve 11 flows in a laminar flow manner, and the fluids in different layers flow separately and are not easy to mix 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, thereby quickly mixing the fluids in different layers and improving the mixing efficiency.

[0061] In a preferred implementation of the embodiment of the present invention, Figure 1-Figure 2 As shown, the mixing unit comprises:

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

[0063] A second gradually diverging channel 112, communicating with a side portion of the first gradually diverging channel 111;

[0064] A gradually contracting bend 113 is connected to the outlet of the first gradually expanding channel 111 and the side of the second gradually expanding channel 112;

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

[0066] Specifically, the mixing unit divides the fluid flowing into the unit inlet into two parts, one part of the fluid enters the first gradually expanding channel 111, and the other part of the fluid enters the second gradually expanding channel 112. The fluid in the first gradually expanding channel 111 enters the tapered bend 113 and returns to the second gradually expanding channel 112. Since the outflow direction of the fluid in the tapered bend 113 is opposite to the outflow direction of the fluid in the second gradually expanding channel 112, it is beneficial for the two parts of the fluid to mix with each other. The gradually expanding channel is beneficial to reducing the pressure and flow rate of the fluid. The first gradually expanding channel 111 is also beneficial for more fluid to enter the tapered bend 113, which is also beneficial to increase the pressure of the fluid in the tapered bend 113. The second gradually expanding channel 112 is also beneficial to reduce the possibility of fluid backflow. The tapered bend 113 is beneficial to increase the pressure and flow rate of the fluid flowing out of the tapered bend 113, which 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 invention, Figure 1 and Figure 3 As shown, the fishbone structure 20 is disposed in the first gradually expanding channel 111 , and the fishbone structure 20 includes: at least one of an outer convex fishbone structure 21 and an inner concave fishbone structure 22 .

[0068] Specifically, the fishbone structure 20 is arranged in the first gradually expanding channel 111, and the fishbone structure 20 can also be arranged in the tapered bend 113 and the second gradually expanding channel 112. Since the first gradually expanding channel 111 is mainly laminar flow, the fishbone structure 20 is arranged in the first gradually expanding channel 111, which is conducive to the mixing of the fluid in the first gradually expanding channel 111. Compared with the tapered bend 113, the size of the first gradually expanding channel 111 is larger, and it is more convenient to arrange the fishbone structure 20. The second gradually expanding channel 112 is the area where the two parts of the fluid are mixed. Compared with the second gradually expanding channel 112, when the fishbone structure 20 is arranged in the first gradually expanding channel 111, the mixing efficiency is more significantly improved.

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

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

[0071] Specifically, since the fluid in the first gradually diverging channel 111 adopts a laminar flow mode, the diversion of the second gradually diverging channel 112 is to divert the fluid in a partial layer area, and the two parts of the diverted fluid will be respectively confined in the first gradually diverging channel 111 and the second gradually diverging channel 112. Therefore, it is necessary to quickly mix the undivided fluid through the fishbone structure 20 before diversion, which is more conducive to improving the mixing efficiency.

[0072] In a preferred implementation of the embodiment of the present invention, Figure 1 and Figure 3 As shown, the mixing unit includes: 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 connected in sequence to form a repeating unit group; the second gradually expanding channel 112 of the first type unit 13 and the second gradually expanding channel 112 of the third type unit 15 are respectively located on the same side of the second gradually expanding channel 112 of the second type unit 14; the second gradually expanding channel 112 of the second type unit 14 and the second gradually expanding channel 112 of the fourth type unit 16 are respectively located on different sides of the second gradually expanding channel 112 of the third type unit 15.

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

[0074] Taking the second gradually expanding channel 112 as a reference, the various types of mixing units are distinguished. The second gradually expanding channel 112 of the first type unit 13, the second gradually expanding channel 112 of the second type unit 14, and the second gradually expanding channel 112 of the third type unit 15 form a trapezoid, so the second gradually expanding channel 112 of the first type unit 13 and the second gradually expanding channel 112 of the third type unit 15 are located on the same side of the second gradually expanding channel 112 of the second type unit 14. The second gradually expanding channel 112 of the second type unit 14, the second gradually expanding channel 112 of the third type unit 15, and the second gradually expanding channel 112 of the fourth type unit 16 form a step shape, so the second gradually expanding channel 112 of the second type unit 14 and the second gradually expanding channel 112 of the fourth type unit 16 are located on both sides of the second gradually expanding channel 112 of the third type unit 15. Of course, the number of mixing units in a single repeating unit group can also be increased, and the direction and position of each mixing unit can be adjusted.

[0075] In a preferred implementation of the embodiment of the present invention, Figure 1 and Figure 3 As shown, the fishbone structure 20 is located in the first gradually expanding channel 111 of the first type unit 13 at a position corresponding to the second gradually expanding channel 112 , or is located in the first gradually expanding channel 111 of the third type unit 15 at a position corresponding to the second gradually expanding channel 112 .

[0076] Specifically, at least one fishbone structure 20 exists in each repeating unit group, and the fishbone structure 20 may be provided in the mixing unit, or may not be provided. For example, in a single repeating unit group, the first type unit 13 and the third type unit 15 are provided with a fishbone structure 20, and the second type unit 14 and the fourth type unit 16 are not provided with a fishbone structure 20. Since the extension direction of the first gradually diverging channel 111 of the first type unit 13 and the extension direction of the first gradually diverging channel 111 of the third type unit 15 are both consistent with the length direction of the Tesla valve 11, and the extension direction of the first gradually diverging channel 111 of the second type unit 14 and the extension direction of the first gradually diverging channel 111 of the fourth type unit 16 are both inconsistent with the length direction of the Tesla valve 11, providing 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 of the embodiment of the present invention, Figure 1 and Figure 2 As shown, the fishbone structure 20 includes:

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

[0079] The first branch portion and the second branch portion are connected to form a sharp angle; the second branch portion is located between the first branch portion and the second gradually expanding channel 112; and the length of the second branch portion is less than the length of the first branch portion.

[0080] Specifically, the fishbone structure 20 is V-shaped, the first branch portion and the second branch portion are connected to each other to form the V-shaped fishbone structure 20, and the connection between the first branch portion and the second branch portion forms the sharp corner of the fishbone structure 20. The length of the first branch portion is longer, and the length of the second branch portion is shorter. The first branch portion is far away from the second gradually diverging channel 112, and the second branch portion is close to the second gradually diverging channel 112. Therefore, the sharp corner of the fishbone structure 20 is closer to the second gradually diverging channel 112, which is more conducive to disturbing and mixing the fluid before the fluid is divided and enters the second gradually diverging channel 112.

[0081] In a preferred implementation of the embodiment of the present invention, the cross-sectional width of the Tesla valve 11 is in the micron level; and the Reynolds number of the fluid in the mixing inlet 12 is in the range of 0 to 10,000.

[0082] Specifically, the cross-sectional width of the Tesla valve 11 is in the micron order, and a micron-sized Tesla valve 11 is formed, and a micro-mixing chip is obtained. The cross-sectional dimension of the fishbone structure 20 is in the micron order, and the cross-sectional dimension of the fishbone structure 20 is smaller than the cross-sectional dimension of the Tesla valve 11. The micro-mixing chip of the fishbone-Tesla valve of the present application has a significant effect on improving the mixing efficiency in the application scenario of low Reynolds number.

[0083] Based on the micro-hybrid chip of the herringbone-Tesla valve described in any of the above embodiments, the present invention also provides a preferred embodiment of a method for preparing a micro-hybrid chip of the herringbone-Tesla valve:

[0084] The method for preparing the micro-hybrid chip of the fishbone-Tesla valve according to the embodiment of the present invention 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 ablation, milling, and 3D printing;

[0087] Step S300: Connect the layer structure and the cover plate to obtain a micro-hybrid chip of a herringbone-Tesla valve.

[0088] Specifically, the materials for manufacturing micro-hybrid chips mainly include metal materials, inorganic materials, polymer materials and paper. Inorganic materials include silicon, glass and ceramics. Polymer materials include elastomeric materials, thermosetting materials, thermoplastic materials and hydrogels. Metal materials are selected from stainless steel, nickel, etc., elastomeric materials are selected from polydimethylsiloxane (PDMS), etc., thermosetting materials are selected from polyester (TPE), etc., and thermoplastic materials are selected from polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene glycol diacrylate (PEGDA), perfluorinated compounds (PFEP / PFA / PFPE), polyurethane (PU), etc. Glass materials have excellent chemical stability and optical transparency, and are often used in applications with high precision or chemical inertness. The three-dimensional structure produced has a high surface finish. Metal materials are suitable for applications that require high temperature resistance or high strength. Metal molds can be made by electroforming, or fine microstructures can be directly processed by micro-milling.

[0089] Photolithography is the process of using light imaging and photosensitive adhesive to pattern the substrate of the micro-hybrid chip, such as silicon, glass and other materials. Its basic process includes: pretreatment, glue coating, pre-baking, exposure, development, hard film, etc. Soft photolithography can cover the mold with PDMS and then mold out a three-dimensional structure, which is suitable for rapid prototyping. The molding method first makes a positive mold (the required channel part is protruding), and then pours the liquid polymer material. The cured polymer material is peeled off from the positive mold to obtain a chip with microchannels. The hot pressing method forms microchannels by heating the plastic sheet and pressing it into the mold, which is suitable for mass production. 3D printing technology based on photosensitive resin or metal powder can also produce complex three-dimensional structures with high flexibility. Different materials have different preparation methods, and materials and preparation methods can be selected according to needs.

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

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

[0092] Step S211, after the substrate is spin-coated with photoresist once and covered with a first mask, the photoresist is exposed and developed once;

[0093] Step S212, after secondary spin coating of the photoresist and covering the second mask, the photoresist is subjected to secondary exposure and secondary development 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.

[0094] Specifically, the Tesla valve and mixed inlet combination with the fishbone structure can be divided into two parts, one part does not contain the fishbone structure, and the other part contains the fishbone structure. Then the mold can also be divided into two parts, one part of the mold contains the fishbone reverse structure, and the other part of the mold does not contain the fishbone reverse structure. When preparing the mold, the part without the fishbone reverse structure is prepared first, and then the part with the fishbone reverse structure is prepared.

[0095] After the photoresist is spin-coated on the substrate once, a first mask is used for exposure, and the first mask is removed and then developed once to obtain a portion without the fishbone inverse structure. Then, after the photoresist is spin-coated twice, a second mask is used for secondary exposure, and the second mask is removed and then developed twice to form a portion containing the fishbone inverse structure on the portion without the fishbone inverse structure, and the remaining photoresist is cured to obtain a mold of a Tesla valve and a mixed inlet combination.

[0096] The fishbone structure includes: an outer convex fishbone structure and an inner concave fishbone structure. The fishbone structure is more complex and the mold preparation steps are more. Step S200 specifically includes:

[0097] Step S221, after the substrate is spin-coated with photoresist once and covered with a first mask, the photoresist is exposed and developed once;

[0098] Step S222, after the photoresist is spin-coated for the second time and covered with the second mask, the photoresist is subjected to secondary exposure and secondary development;

[0099] Step S223, after spin coating the photoresist three times and covering the 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.

[0100] Specifically, the Tesla valve and mixed inlet combination with a fishbone structure can be divided into three parts, the first part does not contain a fishbone structure, the second part contains an inner concave fishbone structure, and the third part contains an outer convex fishbone structure. The mold can also be divided into three parts, the first part of the mold does not contain a fishbone reverse structure, the second part of the mold contains an inner concave fishbone reverse structure, and the third part of the mold contains an outer convex fishbone reverse structure. When preparing the mold, first prepare the part without the fishbone reverse structure, then prepare the part with the inner concave fishbone reverse structure, and finally prepare the part with the outer convex fishbone reverse structure.

[0101] After the photoresist is spin-coated on the substrate once, a first mask is used for exposure, and the first mask is removed and then developed once to obtain a portion without a fishbone inverse structure. Then, the photoresist is spin-coated twice, a second mask is used for exposure, and the second mask is removed and then developed twice to form a portion containing a concave fishbone inverse structure on the portion without a fishbone inverse structure. Then, the photoresist is spin-coated three times, a third mask is used for exposure three times, and the third mask is removed and then developed three times to form a portion containing a convex fishbone inverse structure on the portion containing a concave fishbone inverse structure, and the remaining photoresist is cured to obtain a mold of a Tesla valve and a mixed inlet combination.

[0102] In order to improve the mixing performance of Tesla's micro-hybrid chip, this application adds different fishbone structures above the flow channel to enhance the lateral flow of the fluid and form a spiral flow. Figure 3As shown in the figure, a Tesla micro-mixing chip (TMSHS) with a concave fishbone structure and a Tesla micro-mixing chip (TMRHS) with a convex fishbone structure are designed. The effects of different fishbone structures on the flow trajectory and mixing of the fluid are analyzed by numerical simulation. The T-shaped micro-mixing chip (T-mixer) and the Tesla micro-mixing chip (TM) are used as control examples. The T-shaped micro-mixing chip does not contain a Tesla valve and a fishbone structure, and the Tesla micro-mixing chip contains a Tesla valve but does not contain a fishbone structure. The performance of the four micro-mixing chips, T-mixer, TM, TMSHS and TMRHS, is evaluated over a wide Reynolds number range (Re=0.2-100). The micro-mixing chip is then made using soft lithography technology, and the simulation results are verified by experimental results, proving that the fishbone structure has a significant enhancement effect on mixing.

[0103] Figure 3 The 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 200μm. The length of the mixing inlet and mixing outlet is denoted by W, which is 500μm. The length L of the total channel is 8mm. The height and the inlet width of the second gradually expanding channel are denoted by a, which is 150μm. The outlet of the tapered bend is denoted by b, which is 100μm. The depth of the concave fishbone structure in TMSHS and the height of the convex fishbone structure in TMRHS are denoted by c, which is 50μm. The width of the fishbone structure is denoted by e, which is 65μm. The spacing d between adjacent fishbone structures is 60μm. 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] In the formula, 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] Convection-diffusion equation:

[0114]

[0115] In the formula, c represents the concentration, mol / m 3 ; D represents molecular diffusion rate, m 2 / s.

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

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

[0118]

[0119] Where V is the flow velocity, m / s; d is the hydraulic diameter, m.

[0120] The mixing performance of the micro-hybrid chip is shown by the Mixing Index (MI):

[0121]

[0122] Where σ represents the standard deviation of the outlet concentration, mol / m 3 ;c i Indicates the concentration of each sampling point, mol / m 3 ; represents the concentration of an idealized uniform mixture, mol / m 3 .

[0123] MI ranges from 0 (σ = σ max =0.5) to 1 (σ = 1). Pressure drop (Δp) is the pressure difference before and after the fluid flows in the flow channel, that is:

[0124] Δp=p1-p2 (8)

[0125] Wherein, p1 represents the pressure at the inlet of the main channel, MPa; P2 represents the pressure at the outlet, MPa.

[0126] Grid independence test. Since the numerical simulation results are affected by grid division, it is necessary to verify the grid independence of the model. The TM model with grid numbers ranging from 536775 to 7220161 was tested at Re = 10. Figure 4 The outlet cutoff concentration distribution under different grid numbers is shown. When the grid number increases from 5932360 to 7220161, the curve shape hardly changes. The curve shape with a grid number of 4459551 is also very close to the curve with a grid number of 7220161. The more model grids there are, the longer the calculation time is. In order to ensure the accuracy of the calculation results and improve the calculation efficiency, the division scheme with a grid number of 445955 is selected as the grid division scheme for the four micro-hybrid chips.

[0127] Effect of fishbone structure on mixing. Figure 5 and Figure 7 The changes in the concentration streamlines of the three micro-hybrid chips at Re = 20 are 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 some curved Tesla structure sub-channels, which is also one of the reasons why the overall concentration streamlines in TMSHS are quite different from those of the other two micro-hybrid chips.

[0128] Figure 6 and Figure 8 The velocity of some sections in the micro-mixing chip when Re = 20 is shown, among which the velocity of the TMSHS section is the largest. The concave fishbone structure significantly changes the velocity distribution in the flow channel. The fluid velocity in the convex fishbone is lower than that in the main channel, and does not affect the velocity distribution in the main channel.

[0129] Fig. 9 and Fig.10 The variation of MI with mixing distance at different Re for four micro-mixing chips is shown. When Re is low, mixing is mainly completed by intermolecular diffusion. Fig. 9 (a), (b) and Fig.10 The curves of MI of the four micro-hybrid chips in (a) and (b) are similar as the mixing distance changes. Fig. 9 (c), (d) and Fig.10 In (c) and (d), the MI of the three micro-mixing chips with Tesla structures increases rapidly. However, the MI of the T-mixer does not change significantly. This is because the Tesla structure causes chaotic convection in the fluid, which promotes mixing. The MI of TMSHS and TMRHS is higher than that of TM, which is because the fishbone structure increases the contact area between fluids of different concentrations. Fig. 9 (d) and Fig.10(d) In the first 2 mm mixing length, the MI of TMSHS increases faster than that of TM and TMRHS, which is due to the more intense chaotic convection generated by the concave fishbone structure. The difference in MI between TM and TMRHS is narrowing, which shows that the higher the flow rate, the smaller the effect of the convex fishbone structure on mixing.

[0130] Fig.11 and Fig.12 The concentration distribution of two sections of the micro-mixing chip at different Re is shown. TMSHS and TMRHS take the sections at the same position as TM. As Re increases, the lateral flow of the fluid in the channel is enhanced, generating chaotic convection. Sections A1-A1 and A2-A2 are both at the junction of the two sub-channels of the Tesla structure. Although the section A1-A1 of TMSHS and TMRHS is not close to the fishbone structure, the cross-sectional concentration distribution is different from that of TM. The area of ​​high-concentration fluid wrapped by low-concentration fluid on the side with the fishbone structure is larger, which is caused by the lateral flow caused by the fishbone structure. As Re increases, TMSHS gradually forms vortices in the main channel at section A2-A2, while TMRHS only forms weak vortices at the fishbone structure. Since the concave fishbone structure has a stronger effect on the fluid, the lateral flow of the fluid in the main channel of TMSHS is quite different from that of TM and TMRHS, and stronger chaotic convection is generated, making TMSHS have a stronger promoting effect on fluid mixing.

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

[0132]

[0133] Where, MI HS Indicates the export MI of the micro-hybrid chip with herringbone structure; MI TM Indicates the MI of the TM export.

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

[0135]

[0136] like Fig.13 (d) As Re increases, the MP value decreases continuously, and the MP of TM, TMSHS and TMRHS all exceed that of T-mixer from Re = 10. Among them, the MP of TMRHS is the highest among the three, that is, under the same energy consumption, TMRHS has the best mixing effect.

[0137] In order to verify the mixing performance of the micro-mixing chip, a mixing reaction experiment was carried out using NaOH solution and phenolphthalein solution. A stereo microscope was used to take photos of the solution mixing. The mixing performance of the micro-mixing chip was judged by the uniformity of the pink color formed by the reaction of the two solutions. The more uniform the pink distribution, the better the mixing effect. Fig.14 (a) shows the mixing effect of the micro-mixing chip when Re = 60. The mixing effect of TMSHS and TMRHS is significantly better than that of TM. At the front end of the mixer, it can be clearly seen that the fishbone structure of TMSHS and TMRHS enhances the mixing effect. The fishbone structure changes the flow direction of part of the solution, increases the contact area of ​​the two solutions, and thus improves 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 significantly better than that of TMRSH and TM, which is consistent with Fig. 9 The MI is calculated by measuring the gray value at the exit of the micro-mixing chip. Fig.14 (b) shows the relationship between MI and Re at the outlet of different micro-mixing chips. The trend of the mixing index changing with the increase of Re is the same as that in the simulation. However, due to the influence of the manufacturing precision of the micro-mixing chip and the different diffusion coefficients of the solution, there are certain differences between the experimental results and the simulation.

[0138] The fishbone structure strengthens the lateral flow of the fluid and generates vortices in the channel. The concave fishbone structure can increase the fluid flow rate, has the strongest disturbance to the fluid, and has the best mixing effect. However, due to the greatest obstruction to the fluid, TMSHS has the largest pressure drop. TMRHS has better energy efficiency performance because it ensures interference with 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 disadvantage of low MI of Tesla micro-hybrid chip at lower Re. At Re=5, the η of TMSHS and TMRHS is the highest, 65% and 34% respectively. When Re>30, the influence of the fishbone structure on the mixing results gradually weakens, but the concave fishbone structure can still quickly increase MI in the early stage of mixing. In addition, the mixing experimental results of phenolphthalein solution and NaOH solution confirm the simulation results. This study has guiding significance for improving the mixing performance of micro-mixing chips in a wide Reynolds number range (Re=0-100). 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 micro-mixing chip of the fishbone-Tesla valve of the present application can be applied to drug or liposome mixing, drug or liposome synthesis. Especially for nano-drugs and nano-liposomes, when mixing or synthesizing nano-drugs, mixing or synthesizing nano-liposomes, the micro-mixing chip of the fishbone-Tesla valve of the present application greatly improves the lateral flow of the fluid by combining the fishbone structure and the Tesla valve, and achieves a higher mixing efficiency, which can be applied to the mixing or synthesis of nano-drugs and nano-liposomes. As a drug carrier, liposomes have the functions of sustained release of drugs and reduction of drug toxicity, and can also improve drug stability and targeting.

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

[0141] For example, phosphatidylcholine (PC) of different chain lengths, cholesterol and dihexadecyl phosphate (DCP) are used as components for preparing liposomes. The phosphatidylcholine can be dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dilauroylphosphatidylcholine, etc.

[0142] It should be understood that the application of the present invention is not limited to the above examples. For ordinary technicians in this field, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A micro-hybrid chip of a herringbone-Tesla valve, comprising: The chip body forms a Tesla valve and at least two mixing inlets, wherein the Tesla valve includes at least one mixing unit, and the mixing inlet is connected to the unit inlet of the outermost mixing unit. It is characterized in that at least one mixing unit in the Tesla valve is provided with at least one fishbone structure, and the sharp corner of the fishbone structure faces the mixing inlet.

2. The micro-hybrid chip of the herringbone-Tesla valve according to claim 1, characterized in that: The mixing unit comprises: a first diverging channel having a cell inlet; a second gradually diverging channel, communicating with a side portion of the first gradually diverging channel; a gradually contracting bend communicating with the outlet of the first gradually expanding channel and the side of the second gradually expanding channel; Wherein, an end of the second gradually diverging channel away from the first gradually diverging channel is a unit outlet.

3. The micro-hybrid chip of the herringbone-Tesla valve according to claim 2, characterized in that: The fishbone structure is arranged in the first gradually expanding channel, and the fishbone structure comprises at least one of an outwardly convex fishbone structure and an inwardly concave fishbone structure.

4. The micro-hybrid chip of the herringbone-Tesla valve according to claim 3, characterized in that: The mixed 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 gradually diverging channel of the first type of unit and the second gradually diverging channel of the third type of unit are respectively located on the same side of the second gradually diverging channel of the second type of unit; The second gradually diverging channel of the second type of unit and the second gradually diverging channel of the fourth type of unit are respectively located on different sides of the second gradually diverging channel of the third type of unit.

5. The micro-hybrid chip of the herringbone-Tesla valve according to claim 4, characterized in that: The fishbone structure is located at a position corresponding to the second gradually diverging channel in the first gradually diverging channel of the first type unit, or is located at a position corresponding to the second gradually diverging channel in the first gradually diverging channel of the third type unit.

6. The micro-hybrid chip of the herringbone-Tesla valve according to claim 5, characterized in that: The fishbone structure comprises: a first branch portion and a second branch portion; Wherein, the first branch portion and the second branch portion are connected to form a sharp angle; The second branch portion is located between the first branch portion and the second gradually expanding channel; The length of the second branch portion is smaller than the length of the first branch portion.

7. The micro-hybrid chip of the herringbone-Tesla valve according to claim 6, characterized in that: The cross-sectional width of the Tesla valve is in the micrometer range; The Reynolds number of the fluid at the mixing inlet is 0-10000.

8. A method for preparing a micro-hybrid chip of a herringbone-Tesla valve according to any one of claims 1 to 7, characterized in that: Includes steps: Provide cover plate; Prepare 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 includes: at least one of photolithography, etching, hot pressing, molding, injection molding, laser ablation, milling, and 3D printing; The layer structure and the cover plate are connected to obtain a micro-hybrid chip of a herringbone-Tesla valve.

9. The method for preparing a micro-hybrid chip of a herringbone-Tesla valve according to claim 8, characterized in that: The fishbone structures all adopt an outward convex fishbone structure, or all adopt an inward concave fishbone structure; the preparation layer structure includes: After the substrate is spin-coated with photoresist once and covered with a first mask, the photoresist is exposed and developed once; After secondary spin coating of photoresist and covering the second mask, secondary exposure and secondary development are performed on the photoresist 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; or The fishbone structure includes: an outer convex fishbone structure and an inner concave fishbone structure; the preparation layer structure includes: After the substrate is spin-coated with photoresist once and covered with a first mask, the photoresist is exposed and developed once; After the photoresist is spin-coated for the second time and covered with a second mask, the photoresist is subjected to secondary exposure and secondary development; After the photoresist is spin-coated three times and covered with the 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.

10. Use of a micro-mixing chip of a fishbone-Tesla valve as claimed in any one of claims 1 to 7 in drug or liposome mixing, or drug or liposome synthesis.

Images