WO2023077764A1 - 一种微流控混合器及其应用 - Google Patents

一种微流控混合器及其应用 Download PDF

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WO2023077764A1
WO2023077764A1 PCT/CN2022/092401 CN2022092401W WO2023077764A1 WO 2023077764 A1 WO2023077764 A1 WO 2023077764A1 CN 2022092401 W CN2022092401 W CN 2022092401W WO 2023077764 A1 WO2023077764 A1 WO 2023077764A1
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mixing chamber
mixing
feed
mixer
discharge port
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PCT/CN2022/092401
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English (en)
French (fr)
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招秀伯
许瑞呈
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常州大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms

Definitions

  • the invention relates to the technical field of mixers and applications thereof, in particular to a microfluidic mixer and applications thereof.
  • Microfluidic technology refers to the technology of controlling the flow, mass transfer and heat transfer of fluids with a volume of picoliters to nanoliters in a low-dimensional channel structure with at least one dimension of micron or even nanoscale. It can be widely used in chemical synthesis, Nanoprecipitation, crystallization, molecular self-assembly, biochemical analysis, immunoassay, minimally invasive surgery, environmental monitoring and many other fields. Therefore, some miniature analysis systems or synthesis systems can be implemented on microchips, ie lab-on-a-chip.
  • the devices required for the device or system include microchannels, constant flow pumps/syringe pumps, micromixers, and the like. Can be used for large-scale production of nanoparticles.
  • the microchip may consist of one or more layers. It can be made of glass, silicon, silica gel, metal, plastic and other materials.
  • the characteristic scale of the channel is micron, and the liquid flow rate and Reynolds number are usually low. Therefore, the mixing of fluids is mainly based on the mixing mechanism of laminar flow, and the influence of molecular diffusion is very significant. Therefore, in a certain experiment Under the requirements, the mixing of fluids becomes more difficult; through simple structural design, low-cost micro-mixers can improve the mixing efficiency of fluids and achieve ideal mixing effects. According to literature reports, the current design of micro-mixers is divided into active micro-mixers and passive micro-mixers. Active micro-mixers mainly rely on external power (such as ultrasound, magnetic force, mechanical stirring, etc.) to realize the disturbance of the fluid in the microchannel.
  • external power such as ultrasound, magnetic force, mechanical stirring, etc.
  • the design of the active micro-mixer is complex and expensive; the passive micro-mixer mainly follows the stretching and folding of the fluid channel to increase the contact area between the fluids and promote the diffusion; the passive micro-mixer optimizes the structural design of the micro-channel to achieve The shunting of the liquid or increasing the chaotic convection of the liquid in the channel improves the mixing efficiency; the passive micro-mixer does not require any external power, is easy to process, easy to integrate, and has a fast response speed and is easy to use, so it is widely used.
  • the design variables of a passive micromixer are the geometry and dimensions of the channels, tunnels, which together with the properties of the media and components involved (viscosity, density and diffusivity) and the flow rate determine the pressure drop of the mixer, the Reynolds number, the flow State, state of mixing, efficiency (mixing effect), residence time, number of mixing elements required and necessary volume or area.
  • the Reynolds number increases, the degree of mixing increases, but it will lead to problems such as increased pressure drop. Therefore, a new type of passive micro-mixer is needed to improve mixing efficiency, increase flow, reduce pressure drop, reduce required mixing elements, and reduce volume.
  • the technical problem to be solved by the present invention is to provide a microfluidic mixer and its application in order to overcome the problems of low flow rate, small Reynolds number, low mixing degree and high pressure drop in the passive micromixer in the prior art.
  • a microfluidic mixer including a main body, and the main body is provided with a discharge channel, a number of feed channels and a number of mixing units connected end to end in sequence.
  • the mixing unit includes a first mixing chamber and a second mixing chamber arranged correspondingly to the first mixing chamber, the first mixing chamber is provided with a first discharge port and several first feed ports, and the second mixing chamber is provided with There is a second outlet and a second feed port, the first feed port on the first mixing unit corresponds to the feed channel, the first feed port and the feed channel on the first mixing unit
  • the output end of the first mixing chamber is connected, and the feed channel is arranged tangentially along the outer wall of the first mixing chamber, so that the fluid enters the first mixing chamber tangentially and flows along the inner wall of the first mixing chamber, and the fluid in several feed channels enters the first mixing chamber.
  • the flow direction after the mixing chamber is the same direction;
  • the first discharge port of the first mixing chamber communicates with the second feed port of the corresponding second mixing chamber
  • the second discharge port of two adjacent mixing units corresponds to the first feed port one by one, the second discharge port of one of the two adjacent mixing units communicates with the other first feed port, and the first The second discharge port is arranged tangentially along the outer wall of the first mixing chamber to which it is connected, so that the fluid enters the first mixing chamber tangentially;
  • the second discharge port located in the last mixing unit communicates with the input end of the discharge channel
  • the cross-sectional area of the first discharge port is smaller than the cross-sectional area of the first mixing chamber
  • the cross-sectional area of the second feeding port is smaller than the cross-sectional area of the second mixing chamber
  • the tangential arrangement of the feed channel makes the
  • the fluid enters the first mixing chamber tangentially and the second outlet of one of the two adjacent mixing units communicates tangentially with the first inlet of the other, and the flow direction of the fluid entering the same first mixing chamber is consistent to form a spiral Circular flow, when the spiral circular flow flows from the first mixing chamber into the second mixing chamber, due to the limitation of the aperture of the first outlet, the spiral circular flow shrinks in the first mixing chamber to speed up the outflow, and expands after entering the second mixing chamber , resulting in very efficient and fast mixing.
  • the main body includes a first plate, a second plate and a third plate connected in sequence, and the first The board, the second board and the third board are all provided with cavities, and the cavities of the first board, the second board and the third board are combined to form a discharge channel, several feed channels and several The mixing unit connected end to end in turn divides the discharge channel, the feed channel and the mixing unit into several cavities on the board, which is convenient for processing and manufacturing.
  • the mixing unit further includes a connecting channel, and the input end of the connecting channel communicates with the first outlet of the first mixing chamber, so The output end of the connecting channel communicates with the second feed port of the second mixing chamber.
  • the material of the main body of the mixer is one or more of glass, silicon, silica gel, metal or plastic.
  • the mixer is prepared by one or more methods in photolithography, laser burning, soft etching technology, injection molding method, drilling, 3D printing or milling technology.
  • the mixer is applied to the synthesis of nanoparticles with uniform particle size, liposome vesicles, lipid nanoparticles, micelles and crystals.
  • the beneficial effect of the present invention is: a microfluidic mixer provided by the present invention, through the tangential arrangement of the feed channel, the fluid enters the first mixing chamber and the second outlet of one of the adjacent two mixing units tangentially It is connected tangentially with another first feed port, and the flow direction of the fluid entering the same first mixing chamber is consistent to form a helical circulation.
  • the helical annular flow shrinks in the first mixing chamber to speed up the outflow, and expands after entering the second mixing chamber, so as to achieve very efficient and rapid mixing.
  • Fig. 1 is the front view structure schematic diagram of the present invention
  • Fig. 2 is a top view structural schematic diagram of the first board of the present invention
  • Fig. 3 is a top view structural schematic diagram of the second board of the present invention.
  • Fig. 4 is a top view structural schematic diagram of the third plate of the present invention.
  • Fig. 5 is the structural representation of the mixing unit of embodiment 1 of the present invention.
  • Fig. 6 is the structural representation of the mixing unit of embodiment 2 of the present invention.
  • Fig. 7 is the structural representation of the mixing unit of embodiment 3 of the present invention.
  • Fig. 8 is a schematic structural view of a mixing unit according to Embodiment 4 of the present invention.
  • Fig. 9 is a schematic structural diagram of the connection of two adjacent mixing units in Embodiment 5 of the present invention.
  • Fig. 10 is a schematic diagram of concentration changes during mixing of the mixing unit of the present invention.
  • Figure 11 is a linear schematic diagram of the simulation of the mixing unit of the present invention.
  • Figure 12 is a result diagram of liposome vesicles prepared in Example 6 of the present invention.
  • Fig. 13 is the result graph of the gelatin nanoparticle prepared by the embodiment of the present invention 7;
  • Fig. 14 is a graph showing the results of silk fibroin nanoparticles prepared in Example 8 of the present invention.
  • main body 11, first plate, 12, second plate, 13, third plate, 2, discharge channel, 3, feed channel, 4, mixing unit, 41, first mixing chamber, 411 , the first material outlet, 412, the first material inlet, 42, the second mixing chamber, 421, the second material outlet, 422, the second material inlet, 43, the connecting channel.
  • Figure 1 is a structural schematic diagram of the present invention, a microfluidic mixer, including a main body 1, the main body 1 is provided with a discharge channel 2, a number of feed channels 3 and a number of mixing units 4 connected end to end in sequence,
  • the mixing unit 4 includes a first mixing chamber 41 and a second mixing chamber 42 arranged correspondingly to the first mixing chamber 41.
  • the first mixing chamber 41 is provided with a first material outlet 411 and several first material inlets. 412
  • the second mixing chamber 42 is provided with a second discharge port 421 and a second feeding port 422, the first mixing chamber 41 is in the shape of a cube, column or cone, and the second mixing chamber 42 is in the shape of a cube, column or cone shape,
  • the first feed port 412 on the first mixing unit 4 corresponds to the feed channel 3 one by one, and the first feed port 412 on the first mixing unit 4
  • the port 412 communicates with the output end of the feed channel 3, and the feed channel 3 is arranged tangentially along the outer wall of the first mixing chamber 41, so that the fluid enters the first mixing chamber 41 tangentially and along the inner wall of the first mixing chamber 41 Flow, the flow directions of the fluids in the several feed channels 3 after entering the first mixing chamber 41 are in the same direction, and the flow directions of the fluids in the same first mixing chamber 41 are both clockwise or counterclockwise;
  • the first discharge port 411 of the first mixing chamber 41 communicates with the second feed port 422 of the corresponding second mixing chamber 42;
  • the second discharge port 421 of two adjacent mixing units 4 is in one-to-one correspondence with the first feed port 412, and the second discharge port 421 of one of the two adjacent mixing units 4 is connected to the other.
  • the first feed port 412 is connected, and the second discharge port 421 is arranged tangentially along the outer wall surface of the first mixing chamber 41 to which it communicates, so that the fluid enters the first mixing chamber 41 tangentially;
  • the second discharge port 421 located in the last mixing unit 4 communicates with the input end of the discharge channel 2;
  • the cross-sectional area of the first discharge port 412 is smaller than the cross-sectional area of the first mixing chamber 41
  • the cross-sectional area of the second feeding port 422 is smaller than the cross-sectional area of the second mixing chamber 42, through the feed channel 3
  • the tangential arrangement makes the fluid tangentially enter the first mixing chamber 41 and the second discharge port 421 of two adjacent mixing units 4 communicate with the first feed port 412 tangentially, and enter the same first mixing chamber 41
  • the flow direction of the fluid is consistent to form a helical circulation.
  • the helical circulation shrinks in the first mixing chamber 41 to speed up the outflow. , expands after entering the second mixing chamber 42, thereby achieving very efficient and rapid mixing.
  • Nanoparticles synthesized using this mixer can be applied to, but not limited to, biomedicine, food industry, agriculture, new energy, chemical synthesis, electronic materials, coatings, military and other fields.
  • the main body 1 includes a first plate 11, a second plate 12 and a third plate 13 connected in sequence, and the first plate 11, the second plate 12 and the The third plate 13 is provided with cavities, and the cavity of the first plate 11, the cavity of the second plate 12 and the cavity of the third plate 13 are combined to form the discharge channel 2, some feed channels 3 and some
  • the mixing unit 4 connected end to end in turn divides the discharge channel 2, the feed channel 3 and the mixing unit 4 into several cavities on the board, which is convenient for processing and manufacturing.
  • the main body 1 of the mixer can be composed of at least one plate.
  • a sealing ring is arranged between two adjacent plates.
  • the material of the plates is glass, silicon, silica gel, metal or plastic Etc., preferably high molecular polymer or metal, constitute the cavity of discharge channel 2, several feed channels 3 and some mixing units 4 which are connected end to end in turn, which can be concentrated on one plate, or can be set on at least one plate respectively. on two boards.
  • the mixing unit 4 also includes a connecting channel 43, and the upper input end of the connecting channel 43 communicates with the first discharge port 411 of the first mixing chamber 41, so that The output end of the connecting channel 43 communicates with the second feed port 422 of the second mixing chamber 42, the connecting channel 43 is columnar or conical, and the first mixing chamber 41, the connecting channel 43 and the second mixing chamber 42 form an imitative hourglass shape structure.
  • mixing units connected in series form a group
  • the mixer can include several mixing unit groups, and the mixing unit groups can be connected in series or in parallel to prepare multi-component nanoparticles or expand production capacity.
  • Micromixers are fabricated by photolithography, laser ablation, soft etching techniques, injection molding, drilling, 3D printing, milling, etc.
  • a constant pressure syringe pump can be installed at the input end of the feed channel 3, and the constant pressure syringe pump is used to adjust the mixing speed of the fluid entering the feed channel 3.
  • the main body of the mixer is made of one or more of glass, silicon, silica gel, metal or plastic.
  • the mixer is prepared by one or more methods of photolithography, laser burning, soft etching technology, injection molding method, drilling, 3D printing or milling technology.
  • the mixer is used for fast homogeneous or heterogeneous high-efficiency mixing, artificially synthesized nanoparticles, liposome vesicles, lipid nanoparticles, micelles and crystals, etc., and can be used in most fields that require the participation of nanoparticles, such as Biomedicine, food industry, agriculture, new energy, chemical synthesis, electronic materials, coatings and even military fields, etc.
  • Nanoparticles prepared by the mixer can be applied to, but not limited to, fields such as biomedicine, food industry, agriculture, new energy, chemical synthesis, electronic materials, coatings, and military affairs.
  • the mixer can realize very efficient, fast, and large-scale preparation of nanoparticles, and the required pressure drop is small.
  • the time required for the formation of nanoparticles is 0.1-5 milliseconds, and the particle size is uniform, controllable, and repeatable.
  • the flow rate can be greater than 320mL/min (20L/h).
  • the mixing unit 4 is the first mixing unit, including a first mixing chamber 41, a second mixing chamber 42 and a connecting channel 43, the first mixing chamber 41 is provided with a first discharge port 411 and several The first feed port 412, the second mixing chamber 42 is provided with a second discharge port 421 and a second feed port 422, the first mixing chamber 41 is columnar, the second mixing chamber 42 is columnar, and the connecting channel 43 columnar,
  • the first feed port 412 on the first mixing unit 4 corresponds to the feed channel 3 one by one, the first feed port 412 on the first mixing unit 4 communicates with the output end of the feed channel 3, and the The feed channel 3 is arranged tangentially along the outer wall of the first mixing chamber 41, so that the fluid enters the first mixing chamber 41 tangentially and flows along the inner wall of the first mixing chamber 41, and the fluid in several feed channels 3 enters the first mixing chamber
  • the flow direction after 41 is the same direction, and the flow direction of the fluid in the same first mixing chamber 41 is clockwise.
  • the second feed port 422 of 42 communicates.
  • the mixing unit 4 is the first mixing unit, including a first mixing chamber 41, a second mixing chamber 42 and a connecting channel 43, the first mixing chamber 41 is provided with a first discharge port 411 and several The first feed port 412, the second mixing chamber 42 is provided with a second discharge port 421 and a second feeding port 422, the first mixing chamber 41 is in the shape of a circular truncated table, and the second mixing chamber 42 is in the shape of a circular truncated table, connected to Road 43 is in the shape of a circular platform,
  • the first feed port 412 on the first mixing unit 4 corresponds to the feed channel 3 one by one, the first feed port 412 on the first mixing unit 4 communicates with the output end of the feed channel 3, and the The feed channel 3 is arranged tangentially along the outer wall of the first mixing chamber 41, so that the fluid enters the first mixing chamber 41 tangentially and flows along the inner wall of the first mixing chamber 41, and the fluid in several feed channels 3 enters the first mixing chamber
  • the flow direction after 41 is the same direction, and the flow direction of the fluid in the same first mixing chamber 41 is clockwise.
  • the second feed port 422 of 42 communicates.
  • the mixing unit 4 is the first mixing unit, including a first mixing chamber 41 and a second mixing chamber 42, the first mixing chamber 41 is provided with a first discharge port 411 and a number of first feeding Port 412, the second mixing chamber 42 is provided with a second discharge port 421 and a second feeding port 422, the first mixing chamber 41 is columnar, the second mixing chamber 42 is columnar,
  • the first feed port 412 on the first mixing unit 4 corresponds to the feed channel 3 one by one, the first feed port 412 on the first mixing unit 4 communicates with the output end of the feed channel 3, and the The feed channel 3 is arranged tangentially along the outer wall of the first mixing chamber 41, so that the fluid enters the first mixing chamber 41 tangentially and flows along the inner wall of the first mixing chamber 41, and the fluid in several feed channels 3 enters the first mixing chamber
  • the flow direction after 41 is the same direction, and the flow direction of the fluid in the same first mixing chamber 41 is clockwise.
  • the second feed port 422 of 42 communicates.
  • the mixing unit 4 is the first mixing unit, including a first mixing chamber 41, a second mixing chamber 42 and a connecting channel 43, the first mixing chamber 41 is provided with a first discharge port 411 and several The first feed port 412, the second mixing chamber 42 is provided with a second discharge port 421 and a second feeding port 422, the first mixing chamber 41 is a cube, the second mixing chamber 42 is columnar, and the connecting channel 43 columnar,
  • the first feed port 412 on the first mixing unit 4 corresponds to the feed channel 3 one by one, the first feed port 412 on the first mixing unit 4 communicates with the output end of the feed channel 3, and the The feed channel 3 is arranged tangentially along the outer wall of the first mixing chamber 41, so that the fluid enters the first mixing chamber 41 tangentially and flows along the inner wall of the first mixing chamber 41, and the fluid in several feed channels 3 enters the first mixing chamber
  • the flow direction after 41 is the same direction, and the flow direction of the fluid in the same first mixing chamber 41 is clockwise.
  • FIG. 9 it is a structural schematic diagram of two adjacent mixing units 4 connected, in order to ensure that several mixing units 4 can be at the same level, the first mixing chamber 41 of one of the mixing units 4 is located above the second mixing chamber 42 , wherein the first mixing chamber 41 of another mixing unit is located below the second mixing chamber 42, the second outlet 421 of two adjacent mixing units 4 is in one-to-one correspondence with the first feeding inlet 412, and the adjacent two mixing
  • the second discharge port 421 of one of the units 4 communicates with the first feed port 412 of the other, and the second discharge port 421 is arranged tangentially along the outer wall surface of the first mixing chamber 41 that it communicates with, so that The fluid enters the first mixing chamber 41 tangentially.
  • Embodiment 6 is a diagrammatic representation of Embodiment 6
  • the micro-mixer was used to prepare liposome vesicles, and the principle of anti-solvent-triggered self-assembly was adopted. The steps are as follows:
  • the microfluidic mixer is composed of three high polymer plates, wherein the liquid inlet channel and the liquid outlet channel are on the first plate, and the mixing unit and the mixing channel are on the second plate , and the third board is the substrate.
  • the mixing unit of the microfluidic mixer is shaped like an hourglass.
  • the fluid to be mixed flows into the mixing unit from the inlet, then flows through the upper mixing chamber into the vortex connection hole and then flows out from the lower mixing chamber.
  • the fluid expands as the cross section shrinks, forming a spiral circulation in the micro mixing chamber.
  • the circulatory motion will be accelerated with the contraction of the conical vortex chamber, and the fast-rotating spiral circulation will suddenly expand and flow out from the outlet of the mixing chamber.
  • preparation is used to prepare the precursor solution of liposome, comprises the phosphate buffered saline solution as water phase component and the phospholipid cholesterol molecule alcohol solution as alcohol phase component;
  • Precursor solution preferably adopts 1,2-distearyl Ethanol solution of acid-sn-glycero-3-phosphocholine (DSPC) phospholipid molecule and cholesterol, and the aqueous solution of phosphate is used as buffer;
  • DSPC acid-sn-glycero-3-phosphocholine
  • PBS phosphate-buffered saline
  • step b injects the components of the precursor solution in step b into the micro-mixing chamber in step a respectively through different injection holes, set the total flow rate of the precursor solution, and adjust the phosphate buffered saline
  • the flow rate ratio of the solution to the phospholipid cholesterol molecular alcohol solution is used to collect the product at the outlet hole, and the product is the prepared liposome vesicle.
  • the DSPC/CHOL/EtOH solution and the PBS buffer solution were respectively sucked with a syringe, and injected into the chip with a constant pressure syringe pump. Liposome samples obtained under different total flow rates were collected and stored at 4°C.
  • This example uses a micro-mixer to prepare vesicular liposomes, which is simple to operate, reacts quickly and has a controllable particle size.
  • the particle size and size uniformity of the product can be controlled through simple solvent ratio, flow rate ratio, and total flow rate regulation, and the production equipment is simple. , and the production process is continuous without cumbersome post-processing procedures, which provides the possibility for mass production.
  • Embodiment 7 is a diagrammatic representation of Embodiment 7:
  • the micro-mixer was used to prepare gelatin nanoparticles, and the principle of anti-solvent-induced nano-deposition method was adopted. The steps are as follows:
  • preparing a precursor solution for preparing gelatin nanoparticles including a gelatin solution as an aqueous phase component and an ethanol mixture as an organic phase component.
  • step b injects the components of the precursor solution in step b into the micro-mixing chamber in step a respectively through different injection holes, set the total flow rate of the precursor solution, and adjust the gelatin aqueous solution and The flow rate ratio of the organic phase is used to collect the product at the liquid outlet, and the product is the prepared gelatin nanoparticles.
  • gelatin nanoparticles During the preparation of gelatin nanoparticles in this embodiment, use a syringe to absorb gelatin aqueous solution and 95% ethanol mixed solution respectively, inject the chip with a constant pressure syringe pump, and the injection speed of the preferred gelatin aqueous solution: the injection speed of 95% ethanol mixed solution is 1: 20. Use a vial to collect the gelatin sample obtained under the condition of the flow rate ratio, and store it at 4°C.
  • the gelatin sample obtained in this embodiment was subjected to a dynamic light scattering test to measure the size and polydispersity index of the prepared gelatin nanoparticles.
  • the specific operation steps are as follows:
  • a micro-mixer is used to prepare gelatin nanoparticles.
  • the operation is simple, the reaction is rapid and highly controllable, the production equipment is simple, and the production process is continuous without cumbersome post-processing procedures, which provides the possibility for large-scale production.
  • Embodiment 8 is a diagrammatic representation of Embodiment 8
  • the micro-mixer was used to prepare silk fibroin nanoparticles, and the principle of anti-solvent-induced nano-deposition method was adopted, and the steps were as follows:
  • preparing a precursor solution for preparing silk fibroin nanoparticles including silk fibroin solution as an aqueous phase component and methanol as an organic phase component.
  • the silkworm cocoons were cut into small pieces, and degummed by heating and stirring at high temperature in 0.02M Na 2 CO 3 solution.
  • the degummed silk is rinsed with deionized water to remove sericin.
  • the degummed silk fibers were dried in a drying oven, and then dissolved in Ajisawa reagent.
  • the silk fibroin solution is obtained after dialysis, and finally the obtained silk fibroin solution is centrifuged at high speed to remove particles.
  • the obtained silk fibroin stock solution was diluted with deionized water and stored at 4°C for use.
  • a dynamic light scattering test was performed on the silk fibroin nanoparticle sample obtained in this example, and the size and polydispersity index of the prepared silk fibroin nanoparticle were measured.
  • the specific operation steps are as follows:

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Abstract

一种微流控混合器，包括主体(1)，所述主体(1)内开设有出料道(2)、若干进料道(3)以及若干混合单元(4)，进料道(3)沿第一混合室(41)的外壁面切向布置，使流体切向进入第一混合室(41)并沿第一混合室(41)内壁流动；第二出料口(421)沿其所连通的第一混合室(41)的外壁面切向布置，使流体切向进入第一混合室(41)；第一出料口(411)的横截面面积小于第一混合室(41)的横截面面积，第二进料口(422)的横截面面积小于第二混合室(42)的横截面面积，使进入同一第一混合室(41)内的流体流动方向一致形成螺旋状环流，由于第一出料口(411)的孔径的限制，螺旋状环流在第一混合室(41)收缩加快流出，在进入至第二混合室(42)内后扩张，从而实现非常高效、快速的混合。

Description

一种微流控混合器及其应用 技术领域
本发明涉及混合器技术领域及其应用，尤其是涉及一种微流控混合器及其应用。
背景技术
微流控技术是指在至少有一个维度为微米甚至纳米尺度的低维通道结构中控制体积为皮升至纳升的流体进行流动并传质、传热的技术，可广泛应用于化学合成、纳米沉淀、结晶、分子自组装、生化分析、免疫分析、微创外科手术、环境监测等众多领域。因此，一些微型分析系统或合成系统可以在微芯片即芯片实验室上实现。该装置或系统所需的器件包括微通道、恒流泵/注射器泵、微型混合器等。可用于大规模生产纳米颗粒。该微芯片可由一层或多层构成。可由玻璃、硅、硅胶、金属、塑料等材料构成。
在微流控系统中，通道特征尺度为微米级，液体流速和雷诺数通常较低，因此，流体的混合主要是基于层流的混合机制，而分子扩散的影响十分显著，所以在一定的实验要求之下，流体的混合变得较为困难；通过简单的结构设计，低成本的微混合器可以提升流体的混合效率，达到理想的混合效果。据文献报道，目前微混合器的设计分为主动式微混合器和被动式微混合器，主动式微混合器主要依靠外界动力(如超声、磁力、机械搅拌等)来实现流体在微通道内的扰动，以达到混合效果，主动式微混合器设计复杂且昂贵；被动式微混合器主要遵循拉伸和折叠流体通道来增大流体间接触面积，促进扩散；被动式微混合器通过优化微通道的结构设计，实现液体的分流或增加通道中液体的混沌对流，提高了混合效率；被动式微混合器无需任何外界动力，易于加工，易于集 成，且响应速度快，使用方便，得到广泛应用。
被动式微混合器的设计变量为通道、隧道的几何形状和尺寸，与所涉及的介质和组分的性质(粘度、密度和扩散率)以及流速一起决定了混合器的压降、雷诺数、流动状态、混合状态、效率(混合效果)、停留时间、所需混合元件的数量以及必要的体积或面积。当雷诺数增大时，混合度提升，但会导致压降升高等问题。因此需要一种新型的被动式微混合器，来提高混合效率、增加流量，降低压降、减少所需混合元件、缩小体积等。
发明内容
本发明要解决的技术问题是：为了克服现有技术中被动式微混合器存在流量小，雷诺数小，混合度低以及压降高的问题，提供一种微流控混合器及其应用。
本发明解决其技术问题所采用的技术方案是：一种微流控混合器，包括主体，所述主体内开设有出料道、若干进料道以及若干依次首尾相连通的混合单元，所述混合单元包括第一混合室以及与第一混合室对应布置的第二混合室，所述第一混合室上开设有第一出料口以及若干第一进料口，所述第二混合室上开设有第二出料口以及第二进料口，位于首个混合单元上的第一进料口和进料道一一对应，位于首个混合单元上的第一进料口和进料道的输出端连通，且所述进料道沿第一混合室的外壁面切向布置，使流体切向进入第一混合室并沿第一混合室内壁流动，若干进料道内的流体进入第一混合室后的流动方向为同向；
所述第一混合室的第一出料口和其所对应的第二混合室的第二进料口连通；
相邻两个混合单元的第二出料口和第一进料口一一对应，相邻两个混合单元其中一个的第二出料口和另一个第一进料口连通，且所述第二出料口沿其所连通的第一混合室的外壁面切向布置，使流体切向进入第一混合室；
位于最后一个混合单元的第二出料口和出料道的输入端连通；
所述第一出料口的横截面面积小于第一混合室的横截面面积，所述第二进料口的横截面面积小于第二混合室的横截面面积，通过进料道切向布置使流体切向进入第一混合室以及相邻两个混合单元其中一个的第二出料口和另一个第一进料口切向连通，且进入同一第一混合室内的流体流动方向一致形成螺旋状环流，螺旋状环流从第一混合室流入第二混合室过程中，由于第一出料口的孔径的限制，螺旋状环流在第一混合室收缩加快流出，在进入至第二混合室内后扩张，从而实现非常高效、快速的混合。
为了解决出料道、若干进料道以及若干依次首尾相连通的混合单元生产加工困难的问题，进一步包括所述主体包括依次连接的第一板、第二板以及第三板，所述第一板、第二板以及第三板上均开设有空腔，所述第一板的空腔、第二板的空腔以及第三板的空腔拼合构成出料道、若干进料道以及若干依次首尾相连通的混合单元，将出料道、进料道以及混合单元分隔为若干板上的空腔，便于加工制作。
为了解决同一混合单元的第一混合室和第二混合室连接的问题，进一步包括所述混合单元还包括连接道，所述连接道上输入端和第一混合室的第一出料口连通，所述连接道的输出端和第二混合室的第二进料口连通。
进一步包括该混合器的主体的材质为玻璃、硅、硅胶、金属或塑料中的一种或多种。
进一步包括该混合器采用光刻法、激光烧灼、软刻蚀技术、喷射模塑法、钻孔、3D打印或铣削技术中的一种或多种方法制备。
进一步包括该混合器应用于合成粒径均一的纳米颗粒、脂质体囊泡、脂质纳米颗粒、胶束以及晶体等。
本发明的有益效果是：本发明提供的一种微流控混合器，通过进料道切向布置使流体切向进入第一混合室以及相邻两个混合单元其中一个的第二出料口和另一个第一进料口切向连通，且进入同一第一混合室内的流体流动方向一致形成螺旋状环流，螺旋状环流从第一混合室流入第二混合室过程中，由于第一出料口的孔径的限制，螺旋状环流在第一混合室收缩加快流出，在进入至第二混合室内后扩张，从而实现非常高效、快速的混合。
附图说明
下面结合附图和实施例对本发明进一步说明。
图1是本发明的正视结构示意图；
图2是本发明第一板的俯视结构示意图；
图3是本发明第二板的俯视结构示意图；
图4是本发明第三板的俯视结构示意图；
图5是本发明实施例1的混合单元的结构示意图；
图6是本发明实施例2的混合单元的结构示意图；
图7是本发明实施例3的混合单元的结构示意图；
图8是本发明实施例4的混合单元的结构示意图；
图9是本发明实施例5的相邻两个混合单元连接的结构示意图；
图10是本发明混合单元的混合时浓度变化示意图；
图11是本发明混合单元的混合时模拟线性示意图；
图12是本发明实施例6的制备的脂质体囊泡的结果图；
图13是本发明实施例7的制备的明胶纳米颗粒的结果图；
图14是本发明实施例8的制备的丝素纳米颗粒的结果图。
图中：1、主体，11、第一板，12、第二板，13、第三板，2、出料道，3、进料道，4、混合单元，41、第一混合室，411、第一出料口，412、第一进料口，42、第二混合室，421、第二出料口，422、第二进料口，43、连接道。
具体实施方式
现在结合附图对本发明做进一步详细的说明。这些附图均为简化的示意图，仅以示意方式说明本发明的基本结构，因此其仅显示与本发明有关的构成。
如图1是本发明的结构示意图，一种微流控混合器，包括主体1，所述主体1内开设有出料道2、若干进料道3以及若干依次首尾相连通的混合单元4，所述混合单元4包括第一混合室41以及与第一混合室41对应布置的第二混合室42，所述第一混合室41上开设有第一出料口411以及若干第一进料口412，所述第二混合室42上开设有第二出料口421以及第二进料口422，第一混合室41呈立方体、柱状或锥状，第二混合室42呈立方体、柱状或锥状，
如图5、图6、图7、图8所示，位于首个混合单元4上的第一进料口412和进料道3一一对应，位于首个混合单元4上的第一进料口412和进料道3的输出端连通，且所述进料道3沿第一混合室41的外壁面切向布置，使流体切向进入第一混合室41并沿第一混合室41内壁流动，若干进料道3内的流体进入第一混合室41后的流动方向为同向，流体在同一第一混合室41内的流动方向均为顺时针方向或逆时针方向；
所述第一混合室41的第一出料口411和其所对应的第二混合室42的第二进料口422连通；
如图9所示，相邻两个混合单元4的第二出料口421和第一进料口412一一对应，相邻两个混合单元4其中一个的第二出料口421和另一个的第一进料口412连通，且所述第二出料口421沿其所连通的第一混合室41的外壁面切向布置，使流体切向进入第一混合室41；
位于最后一个混合单元4的第二出料口421和出料道2的输入端连通；
所述第一出料口412的横截面面积小于第一混合室41的横截面面积，所述第二进料口422的横截面面积小于第二混合室42的横截面面积，通过进料道3切向布置使流体切向进入第一混合室41以及相邻两个混合单元4的第二出料口421和第一进料口412切向连通，且进入同一第一混合室41内的流体流动方向一致形成螺旋状环流，螺旋状环流从第一混合室41流入第二混合室过程中，由于第一出料口411的孔径的限制，螺旋状环流在第一混合室41收缩加快流出，在进入至第二混合室42内后扩张，从而实现非常高效、快速的混合。
使用该混合器合成的纳米颗粒可应用于，但不局限于生物医学、食品工业、农业、新能源、化工合成、电子材料、涂料、军事等领域。
如图1、图2、图3、图4所示，所述主体1包括依次连接的第一板11、第二板12以及第三板13，所述第一板11、第二板12以及第三板13上均开设有空腔，所述第一板11的空腔、第二板12的空腔以及第三板13的空腔拼合构成出料道2、若干进料道3以及若干依次首尾相连通的混合单元4，将出料道2、进料道3以及混合单元4分隔为若干板上的空腔，便于加工制作。
该混合器的主体1可有至少由一块板组成，当主体1为至少两块板组成时，相邻两块板之间布置有密封圈，板的材料为玻璃、硅、硅胶、金属或塑料等，优选为高分子聚合物或金属，构成出料道2、若干进料道3以及若干依次首尾相连通的混合单元4的空腔，可集中开设在一块板上，也可分别开设在至少两块 板上。
如图5、图6、图7、图8所示，所述混合单元4还包括连接道43，所述连接道43上输入端和第一混合室41的第一出料口411连通，所述连接道43的输出端和第二混合室42的第二进料口422连通，连接道43呈柱状或锥状，第一混合室41、连接道43与第二混合室42构成仿沙漏状结构。
若干串联的混合单元为组，该混合器能够包括若干混合单元组，混合单元组之间可以串联或并联，以制备多组分纳米颗粒或扩大生产能力。
微混合器通过光刻法、激光烧灼、软刻蚀技术、喷射模塑法、钻孔、3D打印、铣削等方法制备。
可在进料道3的输入端处安装恒压注射泵，恒压注射泵用于调节流体进入进料道3内的混合速度。
该混合器的主体的材质为玻璃、硅、硅胶、金属或塑料中的一种或多种。
该混合器采用光刻法、激光烧灼、软刻蚀技术、喷射模塑法、钻孔、3D打印或铣削技术中的一种或多种方法制备。
该混合器应用于快速均相或非均相高效混合，人工合成纳米颗粒、脂质体囊泡、脂质纳米颗粒、胶束以及晶体等，可应用于需要纳米颗粒参与的大多数领域，如生物医学、食品工业、农业、新能源、化工合成、电子材料、涂料甚至军事领域等。
该混合器制备的纳米颗粒可应用于，但不局限于生物医学、食品工业、农业、新能源、化工合成、电子材料、涂料、军事等领域。
该混合器可实现非常高效、快速、大批量的制备纳米颗粒，且所需压降较小，纳米颗粒的形成所需时间在0.1-5毫秒，粒粒径均一、可控、重复性好，流量可大于320mL/min(20L/h)。
使用时，不同的进料道3分别注入所需混合的不同流体，流体切向进入每个混合单元4，且进入同一混合室内的流体的流动方向一致，从而在第一混合室41内形成螺旋状环流，螺旋状环流在第一混合室41收缩加快流出，在进入至第二混合室42内后扩张，再次切向流入下一个第一混合室41，循环往复直至从出料道2流出，完成混合，如图10、图11所示，其中灰度对比标准为了区分不同流通，使其能够展现混合效果。
实施例1：
如图5所示，该混合单元4为首个混合单元，包括第一混合室41、第二混合室42以及连接道43，所述第一混合室41上开设有第一出料口411以及若干第一进料口412，所述第二混合室42上开设有第二出料口421以及第二进料口422，第一混合室41呈柱状，第二混合室42呈柱状，连接道43呈柱状，
位于首个混合单元4上的第一进料口412和进料道3一一对应，位于首个混合单元4上的第一进料口412和进料道3的输出端连通，且所述进料道3沿第一混合室41的外壁面切向布置，使流体切向进入第一混合室41并沿第一混合室41内壁流动，若干进料道3内的流体进入第一混合室41后的流动方向为同向，流体在同一第一混合室41内的流动方向均为顺时针方向，所述第一混合室41的第一出料口411和其所对应的第二混合室42的第二进料口422连通。
实施例2：
如图6所示，该混合单元4为首个混合单元，包括第一混合室41、第二混合室42以及连接道43，所述第一混合室41上开设有第一出料口411以及若干第一进料口412，所述第二混合室42上开设有第二出料口421以及第二进料口422，第一混合室41呈圆台状，第二混合室42呈圆台状，连接道43呈圆台状，
位于首个混合单元4上的第一进料口412和进料道3一一对应，位于首个 混合单元4上的第一进料口412和进料道3的输出端连通，且所述进料道3沿第一混合室41的外壁面切向布置，使流体切向进入第一混合室41并沿第一混合室41内壁流动，若干进料道3内的流体进入第一混合室41后的流动方向为同向，流体在同一第一混合室41内的流动方向均为顺时针方向，所述第一混合室41的第一出料口411和其所对应的第二混合室42的第二进料口422连通。
实施例3：
如图7所示，该混合单元4为首个混合单元，包括第一混合室41以及第二混合室42，所述第一混合室41上开设有第一出料口411以及若干第一进料口412，所述第二混合室42上开设有第二出料口421以及第二进料口422，第一混合室41呈柱状，第二混合室42呈柱状，
位于首个混合单元4上的第一进料口412和进料道3一一对应，位于首个混合单元4上的第一进料口412和进料道3的输出端连通，且所述进料道3沿第一混合室41的外壁面切向布置，使流体切向进入第一混合室41并沿第一混合室41内壁流动，若干进料道3内的流体进入第一混合室41后的流动方向为同向，流体在同一第一混合室41内的流动方向均为顺时针方向，所述第一混合室41的第一出料口411和其所对应的第二混合室42的第二进料口422连通。
实施例4：
如图8所示，该混合单元4为首个混合单元，包括第一混合室41、第二混合室42以及连接道43，所述第一混合室41上开设有第一出料口411以及若干第一进料口412，所述第二混合室42上开设有第二出料口421以及第二进料口422，第一混合室41呈立方体，第二混合室42呈柱状，连接道43呈柱状，
位于首个混合单元4上的第一进料口412和进料道3一一对应，位于首个混合单元4上的第一进料口412和进料道3的输出端连通，且所述进料道3沿 第一混合室41的外壁面切向布置，使流体切向进入第一混合室41并沿第一混合室41内壁流动，若干进料道3内的流体进入第一混合室41后的流动方向为同向，流体在同一第一混合室41内的流动方向均为顺时针方向。
实施例5：
如图9所示为相邻两个混合单元4连接后的结构示意图，为了保证若干混合单元4能够处于同一水平高度内，其中一个混合单元4的第一混合室41位于第二混合室42上方，其中另一个混合单元的第一混合室41位于第二混合室42下方，相邻两个混合单元4的第二出料口421和第一进料口412一一对应，相邻两个混合单元4其中一个的第二出料口421和另一个的第一进料口412连通，且所述第二出料口421沿其所连通的第一混合室41的外壁面切向布置，使流体切向进入第一混合室41。
实施例6：
在本实例中，使用该微混合器制备脂质体囊泡，采用反溶剂引发的自组装制备原理，其步骤如下：
a.利用微混合器装置，所述微流控混合器由三块高聚合物板组成，其中进液通道和出液通道在第一块板上，混合单元和混合通道在第二块板上，第三块板为基板。所述微流控混合器的混合单元呈仿沙漏状。待混合流体由入口流入混合单元，之后流经上端混合室进入涡旋连接孔再从下端混合室流出，流体随着横截面的缩小再膨胀，在微混合室中形成螺旋状环流。循环运动会随着类圆锥形涡旋室的收缩而加快，快速旋转的螺旋环流再突然膨胀，从混合室流出口流出。
b.配制用于制备脂质体的前驱物溶液，包括作为水相组分的磷酸缓冲盐溶液和作为醇相组分的磷脂胆固醇分子醇溶液；前驱物溶液优选采用1,2-二硬脂 酸-sn-甘油-3-磷酸胆碱(DSPC)磷脂分子与胆固醇的乙醇溶液，并采用磷酸盐的水溶液作为缓冲液；前驱物溶液的制备方法如下：
采用4mg/mL的1,2-二硬脂酸-sn-甘油-3-磷酸胆碱胆固醇乙醇(DSPC/CHOL/EtOH)溶液的制备过程如下：
用分析天平称取8mg的1,2-二硬脂酸-sn-甘油-3-磷酸胆碱和4mg的胆固醇于5mL的西林瓶中，加入3mL无水乙醇混匀，放于4℃的冰箱中保存；
采用浓度为10mM的磷酸缓冲盐溶液(PBS)的配置过程如下：
用分析天平称取8.0g的氯化钠(NaCl)、0.2g的氯化钾(KCl)、0.27g的磷酸二氢钾(KH 2PO 4)和1.14g的磷酸氢二钠(Na 2HPO 4)于烧杯中，加入800mL纯化水，超声混合15min，用校准后的pH计测量溶液，用0.1M的HCl或NaOH调整pH＝7.4±0.05。再将上述溶液倒入1000ml的容量瓶，并用少量的纯化水冲洗烧杯后转移至1000mL的容量瓶定容，转移至1000mL的蜀牛瓶中，放于4℃的冰箱中保存，备用；
用恒压注射泵，将在所述步骤b中的前驱物溶液组分经不同的进样孔分别注入在所述步骤a中微混合室中，设置前驱物溶液的总流速，调节磷酸缓冲盐溶液与磷脂胆固醇分子醇溶液的流速比，在出液孔处收集产物，产物即为所制备出的脂质体囊泡。
本实例脂质体囊泡的制备时用注射器分别吸取DSPC/CHOL/EtOH溶液，和PBS缓冲液，用恒压注射泵注入芯片，优选前驱物溶液总流速为28～320mL/min，用西林瓶收集不同总流速条件下获得的脂质体样品，放于4℃条件下存储。
实验测试分析
对本实例所得脂质体样品，进行动态光散射测试，测量所制备的脂质体的大小，多分散指数。具体的操作步骤如下所述：
将以上做制备好的样品，每组取1mL产物于比色皿中，放于动态光散射仪器中测试。如图12所示，可以看出本发明所提供微混合器用于制备脂质体囊泡，得到的产品尺寸更加均匀。
本实例利用微混合器制备囊泡脂质体，操作简单，反应迅速并且粒度可控，通过简单的溶剂配比、流速比、总流速调控可以控制产品的粒径以及尺寸均匀性，生产设备简单，并且生产过程连续没有繁琐的后处理工序，为大规模生产提供了可能。
实施例7：
本实例与实例6基本相同，特别之处在于：
在本实例中，使用该微混合器制备明胶纳米颗粒，采用反溶剂引发的纳米沉积法制备原理，其步骤如下：
a.本步骤与实例6相同；
b.配制用于制备明胶纳米颗粒的前驱物溶液，包括作为水相组分的明胶溶液和作为有机相组分的乙醇混合液。
采用2％w/v的明胶水溶液的制备过程如下：
用分析天平称取0.2mg的明胶加入10mL的去离子水，40℃加热搅拌，持续搅拌待明胶完全溶解得到透明澄清溶液，用0.1M的NaOH将明胶水溶液的pH值调为碱性溶液，温度保持40℃。
采用浓度为的95％乙醇溶液的配置过程如下：
用量筒量取95mL的无水乙醇加入5mL的去离子水，混匀，于常温保存，备用；
用恒压注射泵，将在所述步骤b中的前驱物溶液组分经不同的进样孔分别注入在所述步骤a中微混合室中，设置前驱物溶液的总流速，调节明胶水溶液 与有机相的流速比，在出液孔处收集产物，产物即为所制备出的明胶纳米颗粒。
本实施例明胶纳米颗粒的制备时用注射器分别吸取明胶水溶液，和95％的乙醇混合液，用恒压注射泵注入芯片，优选明胶水溶液的注射速度：95％的乙醇混合液注射速度为1:20，用西林瓶收集该流速比条件下获得的明胶样品，放于4℃条件下存储。
实验测试分析
对本实施例所得明胶样品，进行动态光散射测试，测量所制备的明胶纳米颗粒的大小，多分散指数。具体的操作步骤如下所述：
将以上做制备好的样品，取1mL产物于比色皿中，放于动态光散射仪器中测试。如图13所示，可以看出本发明所提供微混合器用于制备明胶纳米颗粒，得到的产品尺寸更加均匀。
本实例利用微混合器制备明胶纳米颗粒，操作简单，反应迅速并且高度可控，生产设备简单，并且生产过程连续没有繁琐的后处理工序，为大规模生产提供了可能。
实施例8：
本实例与实例7基本相同，特别之处在于：
在本实施例中，使用该微混合器制备丝素纳米颗粒，采用反溶剂引发的纳米沉积法制备原理，其步骤如下：
a.本步骤与实施例7相同；
b.配制用于制备丝素纳米颗粒的前驱物溶液，包括作为水相组分的丝素溶液和作为有机相组分的甲醇。
丝素水溶液的制备过程如下：
将家蚕茧切成小块，在0.02M Na 2CO 3溶液中，高温加热搅拌脱胶。脱胶丝 用去离子水漂洗，去除丝胶蛋白。将脱胶丝纤维于干燥箱干燥，再溶解于Ajisawa试剂。通过透析后得到丝素溶液，最后将得到的丝素溶液高速离心以去除微粒。得到的丝素原液用去离子水稀释，4℃保存后使用。
有机相采用无水甲醇。
用恒压注射泵，将在所述步骤b中的前驱物溶液组分经不同的进样孔分别注入在所述步骤a中微混合室中，设置前驱物溶液的总流速，调节丝素水溶液与有机相的流速比，在出液孔处收集产物，产物即为所制备出的丝素纳米颗粒。
本实例丝素纳米颗粒的制备时用注射器分别吸取丝素水溶液，和无水甲醇，用恒压注射泵注入芯片，优选前驱物溶液总流速为10～320mL/min，用西林瓶收集以上五组流速比条件下获得的丝素纳米样品，放于4℃条件下存储。
实验测试分析
对本实例所得丝素纳米颗粒样品，进行动态光散射测试，测量所制备的丝素纳米颗粒的大小，多分散指数。具体的操作步骤如下所述：
将以上做制备好的样品，每组取1mL产物于比色皿中，放于动态光散射仪器中测试。如图14所示中得到的结果，可以看出本发明所提供微混合器用于制备丝素纳米颗粒，得到的产品尺寸更加均匀。
以上述依据本发明的理想实施例为启示，通过上述的说明内容，相关工作人员完全可以在不偏离本项发明技术思想的范围内，进行多样的变更以及修改。本项发明的技术性范围并不局限于说明书上的内容，必须要根据权利要求范围来确定其技术性范围。

Claims (7)

  1. 一种微流控混合器，其特征是，包括主体(1)，所述主体(1)内开设有出料道(2)、若干进料道(3)以及若干依次首尾相连通的混合单元(4)，所述混合单元(4)包括第一混合室(41)以及与第一混合室(41)对应布置的第二混合室(42)，所述第一混合室(41)上开设有第一出料口(411)以及若干第一进料口(412)，所述第二混合室(42)上开设有第二出料口(421)以及第二进料口(422)，
    位于首个混合单元(4)上的第一进料口(412)和进料道(3)一一对应，位于首个混合单元(4)上的第一进料口(412)和进料道(3)的输出端连通，且所述进料道(3)沿第一混合室(41)的外壁面切向布置，使流体切向进入第一混合室(41)并沿第一混合室(41)内壁流动，若干进料道(3)内的流体进入第一混合室(41)后的流动方向为同向；
    所述第一混合室(41)的第一出料口(411)和其所对应的第二混合室(42)的第二进料口(422)连通；
    相邻两个混合单元(4)其中一个的第二出料口(421)和另一个第一进料口(412)一一对应，相邻两个混合单元(4)的第二出料口(421)和第一进料口(412)连通，且所述第二出料口(421)沿其所连通的第一混合室(41)的外壁面切向布置，使流体切向进入第一混合室(41)；
    位于最后一个混合单元(4)的第二出料口(421)和出料道(2)的输入端连通；
    所述第一出料口(412)的横截面面积小于第一混合室(41)的横截面面积，所述第二进料口(422)的横截面面积小于第二混合室(42)的横截面面积。
  2. 如权利要求1所述的一种微流控混合器，其特征在于：所述主体(1)包括依次连接的第一板(11)、第二板(12)以及第三板(13)，所述第一板(11)、 第二板(12)以及第三板(13)上均开设有空腔，所述第一板(11)的空腔、第二板(12)的空腔以及第三板(13)的空腔拼合构成出料道(2)、若干进料道(3)以及若干依次首尾相连通的混合单元(4)。
  3. 如权利要求1所述的一种微流控混合器，其特征在于：所述混合单元(4)还包括连接道(43)，所述连接道(43)上输入端和第一混合室(41)的第一出料口(411)连通，所述连接道(43)的输出端和第二混合室(42)的第二进料口(422)连通。
  4. 如权利要求1所述的一种微流控混合器，其特征在于：该混合器的主体的材质为玻璃、硅、硅胶、金属或塑料中的一种或多种。
  5. 如权利要求1所述的一种微流控混合器，其特征在于：该混合器采用光刻法、激光烧灼、软刻蚀技术、喷射模塑法、钻孔、3D打印或铣削技术中的一种或多种方法制备。
  6. 一种微流控混合器的应用，其特征在于：该混合器应用于快速均相或非均相高效混合。
  7. 如权利要求6所述的一种微流控混合器，其特征在于：该混合器应用于合成粒径均一的纳米颗粒、脂质体囊泡、脂质纳米颗粒、胶束以及晶体。
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