A microreactor based on a droplet network and a preparation method thereof

Abstract

The present invention belongs to the field of droplet networks and the preparation of droplet microreactors, and relates to a method for preparing a surfactant-stabilized droplet formed by the cooperative assembly of two-phase polymers and using a droplet network composed of such droplets as a template to prepare a microreactor. In the present invention, a water-soluble polymer grafted with a host molecule and a reactant substrate are fully dissolved in water, and an oil-soluble polymer grafted with a guest molecule is dissolved or dispersed in an organic solvent. The two polymers are cooperatively assembled through host-guest interactions to form a surfactant that successfully stabilizes water droplets in the oil phase. A droplet network microreactor is obtained by manual extrusion. The surfactant used in the present invention is stable, avoids the participation of lipids and the formation of an interfacial bilayer, and the dosage is much lower than that of lipid surfactants. Moreover, the interior is truly interconnected, improving the reaction rate. At the same time, since the droplet size used is relatively large, it can be manually operated, avoiding the design of complex chips, and the reactor form has diversity.

Description

Technical Field

[0001] The present invention belongs to the fields of droplet networks and the preparation of droplet microreactors, and relates to a method for preparing a microreactor using a surfactant-stabilized droplet formed by the cooperative assembly of a two-phase polymer based on host-guest interactions and using a droplet network composed of such droplets as a template. Background Art

[0002] A droplet network, that is, a network pattern composed of droplets, has collective properties that cannot be achieved in a single droplet. Small two-dimensional droplet networks have formed "soft" biological devices, which can be used as electronic components, optical sensors, and batteries. A major breakthrough is the development of droplet printers, which can create patterned three-dimensional droplet networks composed of hundreds to thousands of connected droplets. The three-dimensional droplet network can change its shape, or transmit electrical signals through a defined path, or express proteins under patterned illumination. Due to the diversity of droplet network patterns and functions, there are huge potential applications in bioelectrochemistry, bio-microreactors, bionic tissues, etc., and extensive research has been carried out in recent years. However, the formation of droplet networks often depends on the presence of a lipid bilayer at the water-oil interface. It can be said that the droplets are not completely interconnected, and the rate of mass transfer is highly dependent on the lipid bilayer itself and the embedded special membrane proteins. Moreover, the volume of the droplets constituting the droplet network is often in the nanoliter or even picoliter range, and manual operation is very difficult and often requires the assistance of microfluidic devices. Therefore, there is an urgent need to develop a droplet network that is truly interconnected internally, can be scaled up to microliters and above, and can be simply manually operated.

[0003] Droplet microreactors have the characteristics of being extremely small in volume, the reactants can be concentrated in the droplets, avoiding cross-contamination, and having mild reaction conditions. They are an ideal microreactor and are widely used in the preparation of nanomaterials, enzyme-catalyzed reactions, organic synthesis, and other fields. At present, microreactors based on droplet networks are highly dependent on the movement of the lipid bilayer at the interface. Due to the presence of the lipid membrane, the overall mass transfer rate is slow, and the form of the droplet network often requires precise control by a microfluidic chip. If one wants to increase the mass transfer rate of the microreactor and endow the droplet network microreactor with more flexible operating performance, it is crucial to develop a method for preparing a droplet network that does not involve the stabilization of the lipid bilayer at the interface and is truly interconnected internally. Summary of the Invention

[0004] One of the objectives of the present invention is to provide a method for forming a droplet network stabilized by a two-phase polymer network surfactant to replace the traditional interfacial bilayer surfactant without the need for a complex microfluidic chip design; another objective is to provide a method for preparing a microreactor based on the droplet network. The present invention uses a surfactant-stabilized macroscopic droplet assembled by a two-phase polymer through host-guest interaction forces, and then through manual extrusion, partial fusion occurs between the droplets to obtain a droplet network with a controllable pattern. Reaction substrates are added to different droplets, and when the droplet network is formed, some chemical reactions start in the microreactor.

[0005] To achieve the above objectives, the present invention adopts the following technical solutions:

[0006] A method for preparing a microreactor based on a droplet network provided by the present invention includes the following steps:

[0007] S1) Dissolve or disperse the reaction substrate and the water-soluble polymer grafted with the host molecule in ultrapure water to prepare an aqueous mixed solution;

[0008] S2) Dissolve or disperse the oil-soluble polymer grafted with the guest molecule in an organic solvent to prepare a polar oil-phase mixed solution;

[0009] S3) Dropwise add the aqueous mixed solution prepared in step S1) into the oil-phase mixed solution prepared in step S2), wait for the water-soluble polymer and the oil-soluble polymer to assemble on the interface through the specific recognition of the host molecule and the guest molecule for 15 - 25 minutes, and then manually move the droplets of the aqueous mixed solution with a dropper until the droplets of the aqueous mixed solution come into contact with each other, causing partial fusion between the droplets of the aqueous mixed solution to obtain a microreactor of an aqueous mixed solution droplet network and simultaneously initiate chemical reactions in the reactor.

[0010] In the above method for preparing a microreactor, the water-soluble polymer is one or more of sodium carboxymethylcellulose, hyaluronic acid, sodium hyaluronate, polyethyleneimine, polyacrylic acid, polyvinyl alcohol, and hydroxyethyl cellulose.

[0011] In the above method for preparing a microreactor, the weight of the water-soluble polymer is 0.05 - 5% of the weight of the aqueous mixed solution.

[0012] In the above method for preparing a microreactor, the guest molecule is one or more of viologen and its derivatives, ferrocene and its derivatives, azobenzene and its derivatives, naphthalene and its derivatives, pyrene and its derivatives, and adamantane and its derivatives, and the weight of the guest molecule is 0.01 - 2% of the weight of the polar oil-phase mixed solution.

[0013] The preparation method of the above-mentioned microreactor, wherein the host molecule is one or more of α-cyclodextrin and its derivatives, β-cyclodextrin and its derivatives, γ-cyclodextrin and its derivatives, cucurbit[7]uril and its derivatives, cucurbit[8]uril and its derivatives, pillararenes and their derivatives, and calixarenes and their derivatives, and the weight of the host molecule is 0.01-2% of the weight of the aqueous phase mixture.

[0014] The preparation method of the above-mentioned microreactor, wherein the oil-soluble polymer is one or more of polystyrene, polymethyl methacrylate, polylactic acid, polycaprolactone, and 2-hydroxyethyl acrylate, and the weight of the oil-soluble polymer is 0.03-1% of the weight of the polar oil phase mixed solution.

[0015] The preparation method of the above-mentioned microreactor, wherein the polar organic solvent is one or two of toluene, dichloromethane, chloroform, and carbon tetrachloride.

[0016] The preparation method of the above-mentioned microreactor, wherein the reaction substrate is one or more of ferric chloride, potassium thiocyanate, cobalt chloride hexahydrate, 2-methylimidazole, zinc nitrate hexahydrate, glucose, glucose oxidase, horseradish peroxidase, hydrogen peroxide, and catechol, and the weight of the reaction substrate is 0.005-0.5% of the weight of the aqueous phase mixed solution.

[0017] The preparation method of the above-mentioned microreactor, wherein the volume of the droplets forming the droplet network is 3-10 μL.

[0018] A microreactor based on a droplet network, wherein the microreactor is a microreactor based on a droplet network prepared by the above-mentioned preparation method.

[0019] The beneficial effects of the present invention are as follows:

[0020] (1) The present invention develops a method for forming surfactant-stabilized droplets by the cooperative assembly of two-phase polymers through host-guest interactions, and obtaining a microreactor based on a droplet network by controlling partial fusion of the droplets. The surfactant is simple and stable, avoiding the participation of lipids and the formation of bilayers, and the dosage is much lower than that of lipid surfactants.

[0021] (2) The microreactor formed with such a droplet network as a template has the advantage of truly internal penetration compared with other droplet network microreactors. The mass transfer does not depend on the movement of the bilayer at the interface, improving the mass exchange rate and the reaction rate in the microreactor.

[0022] (3) Since the volume of the droplets used is one or more orders of magnitude larger than that of the droplets prepared by traditional microfluidics, it is convenient for manual operation, avoiding complex microfluidic chip design, and the resulting droplet microreactors have a variety of forms. Description of the Drawings

[0023] Figure 1 Macrophotograph of the droplet network microreactor prepared in Example 1;

[0024] Figure 2 Macrophotograph of the droplet network microreactor prepared in Example 2;

[0025] Figure 3 Macrophotograph of the droplet network microreactor prepared in Example 3;

[0026] Figure 4 Transmission electron micrograph of the ZIF-67 material prepared in Example 2;

[0027] Figure 5 Transmission electron micrograph of the ZIF-8 material prepared in Example 3. Detailed implementation manners

[0028] The present invention will be further described below in conjunction with specific embodiments. Obviously, the described embodiments are only some preferred embodiments of the present invention, and the present invention is not limited to these embodiments. The raw materials used in the following embodiments can be obtained from conventional commercial channels without special instructions.

[0029] Example 1

[0030] First, sodium carboxymethyl cellulose modified with viologen (CMC-MV 2+ ) was dissolved in ultrapure water, and then cucurbit[8]uril (CB[8]) solid was added thereto, and ultrasonic treatment was performed for 10 min to obtain a polymer homogeneous solution grafted with CB[8] host molecules. Subsequently, the solution was divided into two parts, and ferric chloride and potassium thiocyanate, the reaction substrates, were respectively added thereto, and after complete dissolution, two aqueous phase mixed solutions were obtained. Among them, the mass fraction of CMC-MV 2+ in the aqueous phase mixed solution containing CMC-MV 2+ was 0.1%, the mass fraction of CB[8] in the aqueous phase mixed solution containing CB[8] was 0.05%, the mass fraction of ferric chloride in the aqueous phase mixed solution was 0.1%, and the mass fraction of potassium thiocyanate in the aqueous phase mixed solution was 0.1%. Separately, poly(L-lactic acid) modified with azobenzene (Azo-PLLA) was dissolved in toluene to obtain a polar oil phase mixed solution, and the mass fraction of Azo-PLLA in the polar oil phase mixed solution was 0.1%. 5 μL of each of the two aqueous phase mixed solutions was respectively dropped into a petri dish containing 5 mL of toluene phase in the form of droplets, and at room temperature, the water-soluble polymer and the oil-soluble polymer were allowed to assemble through specific recognition of host molecules and guest molecules for 20 min. A common dropper was used to move one of the droplets to make it contact with another droplet. While obtaining the droplet microreactor, the color reaction of ferric ions started to occur.

[0031] Example 2

[0032] The specific implementation steps are the same as those in Example 1, where the reaction substrates are 2-methylimidazole and cobalt chloride hexahydrate.

[0033] Example 3

[0034] The specific implementation steps are the same as those in Example 1, where the reaction substrates are 2-methylimidazole and zinc nitrate hexahydrate.

[0035] Performance Test

[0036] (1) Macroscopic Photos

[0037] Use a camera to take pictures of the macroscopic states of the droplets used in Examples 1 to 3 before and after the formation of the droplet network. The results are shown in Figures 1 to 3 , corresponding to Examples 1 to 3 respectively. It can be seen from Figure 1 that a color reaction between ferric chloride and potassium thiocyanate occurred in the microreactor, and the inside of the droplet changed from colorless to blood red. It can be seen from Figure 2 that the blue-violet nanomaterial ZIF-67 was synthesized in the microreactor. It can be seen from Figure 3 that the white nanomaterial ZIF-8 was synthesized in the microreactor.

[0038] (2) Transmission Electron Microscope Images (TEM)

[0039] Use an HT-7700 transmission electron microscope to analyze the morphology of the nanomaterials prepared in Examples 2 to 3, with an acceleration voltage of 100 kV. The test results are shown in Figures 4 to 5 . It can be seen from Figures 4 to 5 that dodecahedral nanomaterials with relatively uniform particle size distributions were prepared in Examples 2 to 3.

[0040] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to the above-disclosed technical content to obtain equivalent embodiments with equivalent changes, but as long as the content does not depart from the technical solution of the present invention, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A preparation method of a microreactor based on a droplet network, characterized in that, It includes the following steps: S1) Dissolve or disperse the reaction substrate and the water-soluble polymer grafted with the host molecule in ultrapure water to prepare an aqueous phase mixed solution; wherein, the host molecule is one or more of α-cyclodextrin and its derivatives, β-cyclodextrin and its derivatives, γ-cyclodextrin and its derivatives, cucurbit[7]uril and its derivatives, cucurbit[8]uril and its derivatives, pillararene and its derivatives, and calixarene and its derivatives, and the weight of the host molecule is 0.01-2% of the weight of the aqueous phase mixture; S2) Dissolve or disperse the oil-soluble polymer grafted with the guest molecule in an organic solvent to prepare a polar oil phase mixed solution; wherein, the guest molecule is one or more of viologen and its derivatives, ferrocene and its derivatives, azobenzene and its derivatives, naphthalene and its derivatives, pyrene and its derivatives, and adamantane and its derivatives, and the weight of the guest molecule is 0.01-2% of the weight of the polar oil phase mixed solution; S3) Dropwise add the aqueous phase mixed solution prepared in step S1) into the oil phase mixed solution prepared in step S2), wait for 15-25 minutes for the water-soluble polymer and the oil-soluble polymer to assemble on the interface through the specific recognition of the host molecule and the guest molecule, and then manually move the droplets of the aqueous phase mixed solution with a dropper until the droplets of the aqueous phase mixed solution come into contact with each other, causing partial fusion between the droplets of the aqueous phase mixed solution to obtain a droplet network microreactor and the chemical reaction in the reactor occurs simultaneously; wherein, the volume of the droplets forming the droplet network is 3-10 μL.

2. The preparation method of the microreactor based on a droplet network according to claim 1, wherein The water-soluble polymer is one or more of sodium carboxymethyl cellulose, hyaluronic acid, sodium hyaluronate, polyethyleneimine, polyacrylic acid, polyvinyl alcohol, and hydroxyethyl cellulose.

3. The preparation method of the microreactor based on the droplet network according to claim 1, characterized in that, The weight of the water-soluble polymer is 0.05-5% of the weight of the aqueous phase mixed solution.

4. The preparation method of the microreactor based on a droplet network according to claim 1, characterized in that, The oil-soluble polymer is one or more of polystyrene, polymethyl methacrylate, polylactic acid, polycaprolactone, and 2-hydroxyethyl acrylate, and the weight of the oil-soluble polymer is 0.03-1% of the weight of the polar oil phase mixed solution.

5. The preparation method of the microreactor based on a droplet network according to claim 1, characterized in that, The organic solvent is one or two of toluene, dichloromethane, chloroform, and carbon tetrachloride.

6. The preparation method of the microreactor based on a droplet network according to claim 1, characterized in that, The reaction substrate is one or more of ferric chloride, potassium thiocyanate, cobalt chloride hexahydrate, 2-methylimidazole, zinc nitrate hexahydrate, glucose, glucose oxidase, horseradish peroxidase, hydrogen peroxide, and catechol, and the weight of the reaction substrate is 0.005-0.5% of the weight of the aqueous phase mixed solution.

7. A microreactor based on a droplet network, characterized in that, The microreactor is the microreactor prepared by using the preparation method according to any one of claims 1-6.

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