A method for enhancing liquid mixing and reactions in microchannels

Abstract

The application provides a method for strengthening liquid mixing and reaction in a microchannel, and belongs to the field of microfluids and process strengthening. The application can be applied to the fields of chemical substance synthesis, functional material preparation and process strengthening by introducing bubbles into a coaxial microchannel reactor to strengthen liquid mixing and reaction. The coaxial microchannel reactor in the application is composed of an inlet end and a reaction end: the inlet end is composed of three coaxially nested capillaries with different diameters; and the receiving end is composed of two coaxially nested capillaries, wherein the inner capillary is a fluid mixing and reaction area. The innermost capillary of the inlet end of the microreactor is a gas inlet, and the middle and outer capillaries are different liquid inlets. When the gas-liquid two-phase flows into the microreactor at a certain flow ratio, the gas is divided into continuous bubbles by the liquid, at this time, the microreactor is in a gas-liquid multiphase flow with bubbles and liquid bullets in between, and eddies are formed in the liquid bullets to strengthen the liquid mixing, so that the liquid is rapidly mixed and complete, and the reaction process is strengthened.

Description

TECHNICAL FIELD

[0001] The present application relates to mixing and reaction of liquid in microchannels, belonging to the field of microfluidics and process intensification, and in particular to a method for intensifying mixing and reaction of liquid in microchannels. BACKGROUND

[0002] The diameter or equivalent diameter of microchannels is in the order of microns, and the flow rate is mainly in the range of nanoliters per minute to milliliters per minute; therefore, the flow in microchannels is laminar flow, and the mixing of liquid is mainly based on molecular diffusion, resulting in poor mixing effect. However, the degree of mixing of liquid has an important influence on the quality and performance of products in the fields of chemical industry, high-tech materials and biomedicine, and it is crucial to intensify mixing and reaction in microchannels. At present, the methods for enhancing liquid mixing in microchannels mainly include changing the structure of microchannels and introducing external energy, which are called passive mixing and active mixing. The active mixing method is to introduce electric energy, magnetic field, acoustic wave and other energy outside the microchannel to realize efficient mixing of liquid, and to change the velocity flow field and physical properties of liquid by applying external energy to improve the mixing degree of liquid. The advantages of active mixing are that liquid can achieve complete mixing relatively quickly; the disadvantages are that the experimental equipment is required to be high and the experimental equipment is complex to build. The passive method is to change the structure and flow field of microchannels to strengthen liquid mixing, and the principle of passive mixing is to change the flow of liquid to enhance the convective diffusion of liquid to improve the mixing effect of liquid. The advantages of passive mixing method are simple experimental operation and can be applied to a variety of liquids; the disadvantages are that liquid needs to flow for a relatively long distance to achieve good mixing effect, and the processing and manufacturing of micro-mixer are relatively difficult and expensive.

[0003] Using microbubbles to strengthen liquid mixing in microchannels provides a new method, which does not need to build a complex experimental table and change the shape of microchannels, but creates a complex velocity flow field by introducing bubbles to strengthen liquid mixing. When the gas phase and liquid phase are injected at the inlet of the microchannel, due to the fact that the viscosity of the liquid phase is much greater than that of the gas phase, within a certain range, the gas phase is cut into uniform-shaped bubbles by the liquid phase, which exists as a dispersed phase, and the liquid exists as a continuous phase. The gas-liquid flow in the microchannel will form bubble flow, Taylor flow and annular flow according to the flow ratio of the two phases and other conditions. The characteristic of Taylor flow is that the bubbles are separated by the liquid phase, the size of the bubbles is uniform and the size of the bubbles exceeds the diameter of the microchannel, and at the same time the liquid part between the two bubbles is defined as a liquid bullet. Compared with other flow patterns, the characteristics of Taylor flow are easy to generate, high running stability and good mass transfer efficiency. SUMMARY

[0004] The application aims at controlling chemical reaction process by strengthening mixing in microchannels, and proposes a microchannel liquid mixing reaction strengthening method by introducing bubbles into microchannel liquid to change the liquid flow field distribution and further improve the liquid mixing speed to regulate the reaction process.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the application is as follows:

[0006] The application discloses a method for strengthening liquid mixing and reaction in a microchannel.

[0007] Step 1: The end portions of the inner capillary and the middle capillary are drawn to make the tip of the capillary into a conical structure as the outlet position, and the size of the tip of the inner capillary is smaller than that of the tip of the middle capillary; the tip of the capillary is ground flat to keep the tip of the capillary smooth to avoid affecting the fluid flow pattern.

[0008] The capillary material includes glass, metal and rubber.

[0009] Step 2: The outer capillary is fixed on the substrate by using glue, and after the glue is dried, the middle capillary is inserted into the left end of the outer capillary, and then the inner capillary is inserted into the middle capillary to be nested, and the tip positions of the two capillaries are kept consistent; the right end of the outer capillary is inserted into the receiving tube; finally, the positions of the inner capillary, the middle capillary and the receiving tube are butted to ensure the coaxiality of the microreactor, that is, the four tube spaces are coaxial, and then the positions are fixed by using glue.

[0010] Step 3: The annular gap of the inner capillary and the middle capillary, the middle capillary and the outer capillary is connected with the liquid A and liquid B feeding pipeline respectively, and the flow of the two liquids is controlled by the liquid flow pump, and the connection is sealed by glue, and the coaxial microchannel is prepared. The inner capillary is connected with the gas source, and the flow of the gas is controlled by the gas flow meter; the outlet of the receiving tube is connected with a teflon tube and placed in a sample bottle for collection. The pipeline connection device is generally a T-shaped connection channel or a grooved injection needle.

[0011] The liquid A and liquid B are mutually soluble liquids: the liquid A includes tetrahydrofuran solution, acetone solution, acetonitrile solution, dimethyl sulfoxide solution, aqueous solution and the like; the solute in the liquid A includes polylactic acid-glycolic acid copolymer (PLGA), poly(9,9-dioctylfluorene-co-benzothiadiazole) (PFBT), polyethylene glycol (PEG), methylene blue and the like; the liquid B includes water, ethanol, methanol and the like; the gas includes nitrogen, helium and other gases that do not react with the liquid A and B.

[0012] The teflon tube is connected with the two liquid feeding pipelines of the coaxial microchannel which need to be mixed or reacted.

[0013] Step 4: First, the gas is introduced into the inner capillary, and the flow of the gas in the microchannel is controlled by the gas flow meter; when the whole device is in a normal state, the two liquid injection pumps are started, and the flow of the gas is adjusted by the gas flow meter, and the flow of the liquid is adjusted by the liquid flow pump. The flow of the gas and the liquid A and liquid B is controlled, so that the flow form in the receiving tube is gas-liquid Taylor flow: the gas forms bubbles, the bubbles are separated by the liquid phase, the size of the bubbles is uniform and the size of the bubbles exceeds the diameter of the microchannel, and at the same time, the liquid part between the two bubbles is defined as a liquid bullet, and the liquid A and liquid B form a liquid bullet. When the gas-liquid Taylor flow is formed in the receiving tube, the vortex flow field is formed in the liquid bullet to strengthen the liquid phase mixing, enhance the mixing of the liquid A and liquid B, strengthen the mixing and reaction, realize the synthesis of substances and the preparation of materials. During the reaction, the flow of the gas is 1-4000 μL / min; the flow of the liquid A and B is 1-2000 μL / min.

[0014] Further, for the mixing and reaction of more than two liquids, the number of coaxially nested capillaries at the inlet end can be increased.

[0015] Compared with the prior art, the present application has the following beneficial effects:

[0016] (1) The present application can realize rapid mixing of liquids without preparing a complex microchannel structure by utilizing Taylor bubbles to strengthen the mixing of liquids, which is conducive to the strengthening of the reaction and the easy separation of the gas and liquid reactants.

[0017] (2) The present application can realize rapid mixing of reaction liquid without introducing external electric energy, magnetic energy, light energy, sound energy, heat energy and other fields, which is beneficial to the strengthening of reaction.

[0018] (3) The present application is simple to operate and has certain universality. The gas is introduced through the internal inlet, the liquid is introduced through the middle and the outside to form gas-liquid Taylor flow, and the rapid mixing of mutual soluble liquid and the synthesis of chemical substances, the preparation of functional materials and other applications are realized in the liquid bullet. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 It is an experimental schematic diagram of coaxial microchannels.

[0020] Figure 2 It is an experimental physical diagram of coaxial microchannels.

[0021] Figure 3 It is a concentration gray scale diagram of the liquid bullet at different flow distances. In the diagram, Q is the gas flow rate, and L is the flow distance of the liquid bullet. g

[0022] Figure 4 It is a diagram of the relationship between the mixing index of the liquid bullet and the movement distance. In the diagram, the mixing index Mi is used to represent the strength of the mixing degree: when Mi = 0, it indicates that the liquid does not mix; when Mi = 1, the liquid reaches complete mixing.

[0023] Figure 5 It is a transmission electron microscope (TEM) diagram of polylactic acid-glycolic acid copolymer (PLGA) nanoparticles. DETAILED DESCRIPTION

[0024] The present application will be further described below in combination with specific embodiments.

[0025] Example 1

[0026] The coaxial microchannels of the present embodiment are prepared and experimented according to the following steps:

[0027] Step 1. Design of coaxial microchannels: the inner diameter of the inner glass capillary is 300 μm, the outer diameter is 500 μm, and the tip inner diameter is 50 μm; the inner diameter of the middle glass capillary is 580 μm, the outer diameter is 1000 μm, and the tip inner diameter is 300 μm; the inner diameter of the outer glass capillary is 1100 μm, the outer diameter is 1300 μm, the receiving glass capillary has an inner diameter of 580 μm and an outer diameter of 1000 μm, and the receiving tube length is 10 cm. The capillary is coaxially nested and assembled.

[0028] ​After the capillary coaxial nesting is completed, the pipeline connecting equipment selects the injection needle with a groove: take two injection needles, cut a groove at the bottom of each end of the injection needle, and the groove needs to ensure that the bottom of the needle can be clamped into the capillary. Place the two needles at the annular gap connection of the inner capillary and the middle capillary, and the middle capillary and the outer capillary, respectively. Finally, use epoxy resin glue to seal, and place it to dry for 24 hours before use.

[0029] Step 2. Preparation before experiment: In this example, liquid A is deionized water with methylene blue added, which is used for tracing; liquid B is deionized water. Two 20 mL plastic syringes are used to suck liquid A and liquid B, and the two syringes are fixed on the Harvard flow pump. The two plastic syringes are connected to the injection needles on the coaxial microreactor with 0.5 mm Teflon tube, liquid A is injected into the annular gap between the inner capillary and the middle capillary, and liquid B is injected into the annular gap between the middle capillary and the outer capillary; the inner capillary is connected to the gas flow meter with 0.5 mm Teflon tube; the outlet of the receiving tube is connected to the Teflon tube and connected to the collection bottle.

[0030] Step 3. Start experiment: First, adjust the gas flow meter to control the gas flow, and set the flow rate of liquid A and liquid B to 250 μL / min; then turn on the gas flow meter switch and the flow pump switch in turn, and the Taylor bubble and the liquid bomb start to generate, and the liquid in the liquid bomb starts to mix; select the high-speed camera connected to the OLYMPUS microscope to record the bubble shape and the concentration gray scale of the liquid bomb in the microchannel in real time.

[0031] Step 4. Post-processing of results: After the experiment is completed, observe the concentration gray scale of the liquid bomb taken by the high-speed camera and calculate the mixing degree of the liquid bomb.

[0032] Example 1 studies the mixing of liquid bomb under the gas flow rate of 300 μL / min, 500 μL / min, 1100 μL / min and 1300 μL / min. When the gas flow rate is 1100 μL / min and 1300 μL / min, the gas-liquid Taylor flow is formed in the receiving tube. From Figure 4 It can be seen that the mixing index of the liquid bomb can reach more than 0.98 at the movement distance L = 6 cm, close to complete mixing.

[0033] Example 2

[0034] The coaxial microchannel preparation part of this example is the same as that of Example 1.

[0035] The preparation of PLGA (poly-lactic-glycolic acid copolymer) polymer nanoparticles in the coaxial microchannel based on gas-liquid Taylor flow in this example is as follows:

[0036] Nanoparticles refer to microspheres with a size of 1-1000 nm and a sphericity of approximately 1, and have important applications in the field of materials and the like. Currently, two types of methods commonly used for preparing nanoparticles are emulsion polymerization and nanoprecipitation. The emulsion polymerization method is generally used for preparing nanoparticles with a larger particle size and cannot continuously prepare nanoparticles. The nanoprecipitation method is divided into a direct injection method and a microfluidic technology method, and compared with the direct injection method, the nanoprecipitation method can prepare nanoparticles with a controllable particle size and continuously prepare nanoparticles.

[0037] Step 1. Preparation of a solution: 1 mg of PLGA (poly(lactic-co-glycolic acid)) was weighed and dissolved in 1 mL of THF (tetrahydrofuran) to obtain a polymer solution of PLGA at 30 μg / mL for experimental use.

[0038] Step 2. Preparation before experiment: The coaxial microchannel in Example 1 was selected; liquid A was a PLGA-THF polymer solution at 30 μg / mL, and liquid B was deionized water. 0.5 mL of liquid A was taken by using a glass syringe with a range of 1 mL, the glass syringe was fixed on a Harvard injection pump, and the needle at the annular inlet of the inner capillary and the middle capillary was connected through a four-fluoride tube with an inner diameter of 0.5 mm. 20 mL of liquid B was taken by using a glass syringe with a range of 20 mL, the syringe was fixed on a Harvard injection pump and connected to the needle at the annular inlet of the middle capillary and the outer capillary through a four-fluoride tube with an inner diameter of 0.5 mm. The inner capillary inlet was connected to a gas flow meter through a four-fluoride tube with an inner diameter of 0.5 mm.

[0039] Step 3. Preparation of nanoparticles: the gas flow of the gas flow meter was adjusted to 1100 μL / min, the flow rate of liquid A was 1 μL / min, and the flow rate of liquid B was 500 μL / min. At this time, a gas-liquid Taylor flow was formed in the microchannel, and the mixing of the two liquids in the liquid bomb was intensified and nanoparticles were prepared. The flow process in the microchannel was recorded by using an OLYMPUS microscope and a high-speed camera during the experiment.

[0040] Step 4. Sample treatment and characterization: after the reaction was completed, the collected sample was treated at 50°C by using nitrogen blowing until THF in the sample was removed. Finally, polymer nanoparticles suspended in liquid B were obtained. The sample obtained after removing THF was detected by a dynamic light scattering instrument (DLS) and a transmission electron microscope (TEM), and the particle size of the nanoparticles was 8±2 nm, the size distribution of the nanoparticles was uniform, and the sphericity was close to 1, as shown in FIG. 1. Figure 5

[0041] Example 3

[0042] The coaxial microchannel preparation part of this example is the same as that of Example 1. ​

[0043] The preparation of poly(9,9-dioctylfluorene-co-benzothiadiazole) (PFBT) nanoparticles in the coaxial microchannel based on gas-liquid Taylor flow in this embodiment is as follows:

[0044] Step 1. Preparation of solution: 1 mg of PFBT polymer was weighed and dissolved in 1 mL of tetrahydrofuran (THF) to obtain a polymer solution of PFBT at 30 μg / mL for experimental use.

[0045] Step 2. Preparation before experiment: the microchannel in Example 1 was selected as the coaxial microchannel; liquid A was a PFBT-THF polymer solution at 30 μg / mL, and liquid B was deionized water. 0.5 mL of liquid A was taken with a glass syringe with a range of 1 mL, the glass syringe was fixed on a Harvard syringe pump, and the needle corresponding to the annular inlet of the inner capillary and the middle capillary was connected through a four-fluorotube with an inner diameter of 0.5 mm. 20 mL of liquid B was taken with a plastic syringe with a range of 20 mL, the syringe was fixed on a Harvard syringe pump and connected to the needle corresponding to the annular inlet of the middle capillary and the outer capillary through a four-fluorotube with an inner diameter of 0.5 mm. The inner capillary inlet was connected to a gas flow meter through a four-fluorotube with an inner diameter of 0.5 mm.

[0046] Step 3. Preparation of nanoparticles: the gas flow of the gas flow meter was adjusted to 1100 μL / min, the flow rate of liquid A was 1 μL / min, and the flow rate of liquid B was 500 μL / min. At this time, gas-liquid Taylor flow was formed in the microchannel, and the two liquids were mixed in the liquid bomb to achieve the intensification of nanoparticle preparation. The flow process in the microchannel was recorded with an OLYMPUS microscope and a high-speed camera during the experiment.

[0047] Step 4. Sample processing and characterization: after the reaction was completed, the collected sample was blown with nitrogen at 50°C until the THF in the sample was removed. Finally, the polymer nanoparticles suspended in liquid B were obtained. The sample obtained after the removal of THF was detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and the particle size of the nanoparticles was 10 nm, the size distribution of the nanoparticles was uniform, and the sphericity was close to 1.

[0048] The above embodiments only express the implementation of the present application, but cannot be understood as a limitation on the scope of the patent of the present application. It should be noted that, for those skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are all within the protection scope of the present application.

Claims

1. A method for enhancing liquid mixing and reaction in a microchannel, characterized in that, The method enhances the mixing and reaction of liquids by introducing bubbles into a coaxial microchannel. The coaxial microchannel includes three nested capillaries and a receiving tube. The capillaries, from the inside out, are an inner capillary, a middle capillary, and an outer capillary. The outlets of the inner and middle capillaries are at the same position and are inserted into the receiving tube for a certain distance to ensure that a gas-liquid Taylor flow is formed within the receiving tube. Gas is introduced into the inlet of the inner capillary, and miscible liquids are introduced into the annular gaps of the inner and middle capillaries, as well as the annular gaps of the middle and outer capillaries. The method includes the following steps: Step 1: Draw the ends of the inner capillary and the middle capillary to make their tips tapered, which will serve as the outlet position, and grind the tips of the capillary flat. Step 2: Fix the outer capillary to the substrate, insert the receiving tube from the right end, and insert the middle capillary and inner capillary that are nested and coaxial from the left end, with the tips of the two capillary tubes aligned and inserted 1 to 4 cm into the receiving tube; fix the four tubes after they are coaxial in space. Step 3: Connect the annular gaps of the inner capillary, the middle capillary, and the outer capillary to the feed lines of liquid A and liquid B, respectively, and connect them to the liquid flow pump. Seal the connection points. Connect the inner capillary to the gas source. Connect the outlet of the receiving tube to the receiving bottle. Liquid A and liquid B are miscible liquids. Step 4: First, introduce gas into the internal capillary and control the gas flow rate in the microchannel using a gas flow meter. When the entire device is in a stable state, turn on the two liquid flow pumps and adjust the gas flow rate using the gas flow meter and the liquid flow rate using the liquid flow pumps. By controlling the flow rates of gas and liquid A and liquid B, the flow pattern in the receiving tube is a gas-liquid Taylor flow. During the reaction, the gas flow rate is 1 ~ 4000 μL / min; the fluid flow rates of liquids A and B are 1 ~ 2000 μL / min.

2. The method for enhancing liquid mixing and reaction in a microchannel according to claim 1, characterized in that, For mixing or reacting two or more liquids, the number of coaxially nested capillaries is increased at the inlet end.

3. The method for enhancing liquid mixing and reaction in a microchannel according to claim 1, characterized in that, In step 1, the capillary material includes glass, metal, and rubber.

4. The method for enhancing liquid mixing and reaction in a microchannel according to claim 1, characterized in that, In step 1, the capillary dimensions are as follows: the inner diameter of the inner capillary is 1 ~ 500 μm, the inner diameter of the middle capillary is 300 ~ 800 μm, and the inner diameter of the outer capillary is 600 ~ 1200 μm.

5. The method for enhancing liquid mixing and reaction in a microchannel according to claim 1, characterized in that, Liquid A includes tetrahydrofuran solution, acetone solution, acetonitrile solution, dimethyl sulfoxide solution, and aqueous solution. The solutes in liquid A include polylactic acid-glycolic acid copolymer, poly(9,9-dioctylfluorene-co-benzothiadiazole), polyethylene glycol, and methylene blue. Liquid B includes water, ethanol, and methanol.

6. The method for enhancing liquid mixing and reaction in a microchannel according to claim 1, characterized in that, The gases include nitrogen, helium, or other gases that do not react with liquids A and B.

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