Method for preparing hollow hydrogel through microfluidic-assisted front-end polymerization

Abstract

The invention discloses a method for preparing hollow hydrogel through microfluidic-assisted front-end polymerization, and belongs to the technical field of functional polymer material preparation, and the method comprises the following steps: S1, adding an acrylic monomer, an acrylamide monomer and N, N '-methylene bisacrylamide into a dimethyl sulfoxide solution; s2, adding a thickening agent; s3, adding an initiator and a polymerization inhibitor to prepare a precursor solution of gel, and adding the precursor solution into an injector; s4, stirring gelatin and a solvent, and adding the mixture into an injector; s5, connecting the two injectors, the transparent hose and the coaxial needle, introducing the solution 1 into an outer-layer channel, introducing the solution 2 into an inner-layer channel, adjusting the temperature of the electric soldering iron to 100-120 DEG C when ink is extruded and falls on a platform, heating the outer-layer solution, and stopping heating when a stable end face is presented in the thermal imager; and S6, after the ink on the outer layer is cured, injecting hot water into the inner layer of the fiber by using an injector to remove the gelatin, thereby obtaining the hollow hydrogel. The method has the advantages of high speed, high efficiency, low cost, high forming speed and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of functional polymer materials, and relates to a method for preparing a hydrogel, in particular to a method for preparing a hollow hydrogel by microfluidics-assisted frontal polymerization. Background Art

[0002] Frontal Polymerization is a technology that utilizes in-situ self-propagation. It provides energy for material synthesis by virtue of its own polymerization enthalpy and does not require additional energy supply, greatly reducing energy consumption. During the polymerization process, the monomer is energized for a short time at one end to initiate the monomer reaction, and then the external energy is removed. Then, the high heat release of itself is used to initiate the polymerization of the monomers in the adjacent area. In this way, the reaction area spontaneously moves towards the unreacted area, and finally the monomers in the entire area complete the polymerization reaction. Recently, the combination of frontal polymerization and microfluidics has made beneficial progress in manufacturing complex and delicate structures. Summary of the Invention

[0003] The present invention provides a method for preparing a hollow hydrogel by microfluidics-assisted frontal polymerization to overcome the defects of the prior art.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] A method for preparing a hollow hydrogel by microfluidics-assisted frontal polymerization, comprising the following steps: S1. Add acrylic acid monomer, acrylamide monomer, and N,N'-methylenebisacrylamide crosslinking agent to dimethyl sulfoxide solution and stir to form a homogeneous solution; S2. Then slowly add the thickener Carbomer 940 to the beaker multiple times and stir vigorously at 45 °C until the solution is clear and transparent; S3. After the above solution is cooled to room temperature, add the initiator ammonium persulfate and the inhibitor 2,2,6,6-tetramethylpiperidine-1-oxyl radical, and after stirring and dissolving, prepare a precursor solution of the gel. Ultrasonically remove the bubbles in the solution from the precursor solution, and then add it to a syringe; S4. Weigh gelatin and solvent water and put them into a container, stir at 40 - 50 °C until the solution is clear and transparent, and then add it to a syringe; S5. Use a Luer adapter to connect two screw syringes, a transparent hose, and a coaxial needle. The outer channel is filled with solution 1, and the inner channel is filled with solution 2. Then set the flow rate of the micro-injection pump. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100 - 120 °C, and use a heat gun to heat the outer solution. Stop heating when a stable end face appears in the thermal imager; S6. After the outer ink is cured, use a syringe to inject hot water into the inner layer of the fiber to remove the gelatin and clean the channel, and a hollow hydrogel is obtained.

[0006] To optimize the above technical solutions, the specific measures taken further include:

[0007] Furthermore, the ink is divided into two types, namely, the outer-layer front-end polymerizable ink and the inner-layer gelatin ink; the specific gravity of gelatin in the inner-layer ink is 15-25 wt%.

[0008] Furthermore, the range of the inner and outer needles of the coaxial needle is 14-22 gauge; the inner diameter of the hollow hydrogel is 0.5-0.8 mm; the flow rate ratio of the inner and outer layer injection pumps is 0.25-0.4.

[0009] Furthermore, the specific gravity of acrylamide monomer is 20-40 wt%; the specific gravity of acrylic acid monomer is 18-40 wt%; the specific gravity of N,N'-methylenebisacrylamide is 0.2-0.5 wt%.

[0010] Furthermore, the specific gravity of dimethyl sulfoxide is 35-45 wt%.

[0011] Furthermore, the specific gravity of Carbomer 940 is 2-3 wt%.

[0012] Furthermore, the specific gravity of 2,2,6,6-tetramethylpiperidine-1-oxyl radical is 0.1-0.2 wt%.

[0013] Furthermore, the specific gravity of ammonium persulfate is 0.9-2 wt%.

[0014] Furthermore, the polymerization reaction is a front-end polymerization reaction method.

[0015] Furthermore, the polymerization temperature initiated by the soldering iron is 100-120 °C, and the polymerization time initiated by the soldering iron is 40-60 s.

[0016] The beneficial effects of the present invention are as follows: The present invention provides a method for preparing hollow hydrogels by microfluidics-assisted frontal polymerization. First, an outer layer ink is prepared by dissolving acrylamide, acrylic acid, and N,N'-methylenebisacrylamide in dimethyl sulfoxide liquid and forming a homogeneous solution through magnetic stirring. Then, Carbopol 940 is slowly added to the beaker multiple times and vigorously stirred at 45 °C until the solution is clear and transparent. After the solution is cooled to room temperature, ammonium persulfate as the initiator and 2,2,6,6-tetramethylpiperidine-1-oxyl radical as the inhibitor are added to the beaker. After complete dissolution, the frontal polymerization ink is obtained. The inner layer ink is prepared by dissolving gelatin in water to form a homogeneous solution. The inner and outer inks are degassed under vacuum and then transferred to 20 ml screw-cap syringes respectively, which are fixed on a micro-injection pump. Then, a Luer adapter is used to connect the screw-cap syringe, transparent hose, and coaxial needle. Next, the flow rates of the injection pumps are set respectively, and the inks are extruded using a microfluidic pump. A hot air gun is used to heat the outer layer ink. When the monomers in the outer layer ink start to polymerize upon heating, a stable "front end face" is formed. At this time, the heat source is removed, and the "end face" moves forward along the extrusion direction at a constant speed, ultimately realizing the in-situ curing of layer-by-layer stacking of the ink. After the outer layer ink is cured, hot water is injected into the inner layer of the hydrogel using a syringe to remove the gelatin, thereby obtaining a hollow hydrogel.

[0017] The present invention combines the frontal polymerization technology with the microfluidics technology, providing a new route for the preparation of hollow hydrogels, and it is expected to have practical application value upon popularization. At the same time, the method of the present invention has the advantages of fast speed, high efficiency, low cost, and fast molding, providing a path for the preparation of hollow hydrogels and having high application value in both the biological and chemical engineering fields. Detailed implementation manners

[0018] The present invention is further described below in conjunction with specific embodiments.

[0019] Example 1

[0020] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 50 °C. After the particles dissolve to obtain a light yellow transparent liquid, transfer it to a 20 mL syringe. Meanwhile, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N’-methylenebisacrylamide and 4 g of dimethyl sulfoxide and add them to a 25 ml glass beaker. Stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in multiple portions and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front polymerization ink and then transfer it to a 20 mL syringe. Connect two syringes, a transparent hose and a coaxial needle using a Luer adapter (the gelatin ink passes through the inner layer and the front polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:4. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100 °C, aim the heat gun at the outer layer solution for heating. When a stable end face appears in the thermal imager, stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, thus obtaining a hollow hydrogel. The inner diameter of the obtained hollow hydrogel is 642 μm. The front end temperature is 106 °C and the front end speed is 3.65 cm / min.

[0021] Example 2

[0022] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 45 °C. After the particles dissolve to obtain a light yellow transparent liquid, transfer it to a 20 mL syringe. Meanwhile, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N’-methylenebisacrylamide and 4 g of dimethyl sulfoxide and add them to a 25 ml glass beaker. Stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in multiple portions and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front polymerization ink and then transfer it to a 20 mL syringe. Connect two syringes, a transparent hose and a coaxial needle using a Luer adapter (the gelatin ink passes through the inner layer and the front polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:4. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 110 °C, aim the heat gun at the outer layer solution for heating. When a stable end face appears in the thermal imager, stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, thus obtaining a hollow hydrogel.

[0023] Example 3

[0024] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 40 °C. Wait for the particles to dissolve to obtain a light yellow transparent liquid, and transfer it to a 20 mL syringe. At the same time, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N'-methylenebisacrylamide and 4 g of dimethyl sulfoxide, add them to a 25 ml glass beaker, and stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in multiple portions, and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front-end polymerization ink and then transfer it to a 20 mL syringe. Use a Luer adapter to connect the two syringes, a transparent hose, and a coaxial needle (the gelatin ink passes through the inner layer, and the front-end polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:4. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 120 °C, and use a heat gun to heat the outer layer solution. Wait until a stable end face appears in the thermal imager, and then stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, and a hollow hydrogel is obtained.

[0025] Example 4

[0026] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 50 °C. Wait for the particles to dissolve to obtain a light yellow transparent liquid, and transfer it to a 20 mL syringe. At the same time, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N'-methylenebisacrylamide and 4 g of dimethyl sulfoxide, add them to a 25 ml glass beaker, and stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in multiple portions, and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front-end polymerization ink and then transfer it to a 20 mL syringe. Use a Luer adapter to connect the two syringes, a transparent hose, and a coaxial needle (the gelatin ink passes through the inner layer, and the front-end polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:2.5. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100 °C, and use a heat gun to heat the outer layer solution. Wait until a stable end face appears in the thermal imager, and then stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, and a hollow hydrogel is obtained. The inner diameter of the obtained hollow hydrogel is 642 μm. The front-end temperature is 106 °C, and the front-end speed is 3.65 cm / min.

[0027] Example 5

[0028] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 50 °C. After the particles are dissolved to obtain a light yellow transparent liquid, transfer it to a 20 mL syringe. At the same time, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N'-methylenebisacrylamide and 4 g of dimethyl sulfoxide and add them to a 25 ml glass beaker. Stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in several portions and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front-end polymerization ink and then transfer it to a 20 mL syringe. Connect two syringes, a transparent hose and a coaxial needle with a Luer adapter (the gelatin ink passes through the inner layer and the front-end polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:3. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100 °C, aim the heat gun at the outer layer solution for heating. When a stable end face appears in the thermal imager, stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, and a hollow hydrogel is obtained.

[0029] Example 6

[0030] Weigh 3 g of gelatin and dissolve it in 10 mL of deionized water. Heat and stir at 50 °C. After the particles are dissolved to obtain a light yellow transparent liquid, transfer it to a 20 mL syringe. At the same time, weigh 4 g of acrylamide, 2 g of acrylic acid, 0.03 g of N,N'-methylenebisacrylamide and 4 g of dimethyl sulfoxide and add them to a 25 ml glass beaker. Stir magnetically to form a homogeneous solution. Then slowly add 0.25 g of carbomer 940 to the beaker in several portions and stir vigorously at 45 °C until the solution is clear and transparent. Finally, wait for the solution to cool to room temperature, add 0.1 g of ammonium persulfate and 0.017 g of 2,2,6,6-tetramethylpiperidine-1-oxyl radical to the above solution. After complete dissolution, obtain the front-end polymerization ink and then transfer it to a 20 mL syringe. Connect two syringes, a transparent hose and a coaxial needle with a Luer adapter (the gelatin ink passes through the inner layer and the front-end polymerization ink passes through the outer layer). Then set the flow rate of the micro-injection pump, and the flow rate ratio of the inner and outer layers is 1:3.5. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100 °C, aim the heat gun at the outer layer solution for heating. When a stable end face appears in the thermal imager, stop heating. After the outer layer ink is cured, use a syringe to inject warm water (60 °C) into the inner layer of the fiber to remove the gelatin and clean the channel, and a hollow hydrogel is obtained.

[0031] In the present invention, unless otherwise specified, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Also, the reagents, materials, and operation steps used herein are widely used reagents, materials, and conventional steps in the relevant fields.

[0032] Finally, it should be noted that the above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization, characterized in that: It includes the following steps: S1. Add acrylic acid monomer, acrylamide monomer, and N,N'-methylenebisacrylamide crosslinking agent into dimethyl sulfoxide solution and stir to form a homogeneous solution; S2. Then slowly add the thickener Carbomer 940 into the beaker multiple times, and stir vigorously at 45 °C until the solution is clear and transparent; S3. After the above solution is cooled to room temperature, add ammonium persulfate initiator and 2,2,6,6-tetramethylpiperidine-1-oxyl radical inhibitor. After stirring and dissolving, prepare a precursor solution of the gel. Ultrasonically remove the bubbles in the solution of the precursor solution, and then add it into a syringe; S4. Weigh gelatin and solvent water and put them into a container, stir at 40-50 °C until the solution is clear and transparent, and then add it into a syringe; S5. Use a Luer adapter to connect two screw syringes, a transparent hose, and a coaxial needle. The outer channel is for solution 1, and the inner channel is for solution 2. Then set the flow rate of the micro-injection pump. When the ink is extruded and falls on the platform, adjust the temperature of the soldering iron to 100-120 °C, aim the heat gun at the outer solution for heating, and stop heating when a stable end face appears in the thermal imager; S6. After the outer ink is cured, use a syringe to inject hot water into the inner layer of the fiber to remove the gelatin and clean the channel, and then a hollow hydrogel is obtained.

2. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The ink is divided into two types, the outer front-end polymerization ink and the inner gelatin ink; The specific gravity of gelatin in the inner layer ink is 15-25 wt%.

3. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The range of the inner and outer needles of the coaxial needle is 14-22 gauge; The inner diameter of the hollow hydrogel is 0.5-0.8 mm; The flow rate ratio of the inner and outer layer injection pumps is 0.25-0.

4.

4. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The specific gravity of acrylamide monomer is 20-40 wt%; The specific gravity of acrylic acid monomer is 18-40 wt%; The specific gravity of N,N'-methylenebisacrylamide is 0.2-0.5 wt%.

5. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The specific gravity of dimethyl sulfoxide is 35-45 wt%.

6. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The specific gravity of Carbomer 940 is 2-3 wt%.

7. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The specific gravity of 2,2,6,6-tetramethylpiperidine-1-oxyl radical is 0.1-0.2 wt%.

8. The method for preparing hollow hydrogels by microfluidics-assisted front-end polymerization according to claim 1, characterized in that: The specific gravity of ammonium persulfate is 0.9-2 wt%.

9. The method for preparing hollow hydrogels by microfluidics-assisted frontal polymerization according to claim 1, characterized in that: The polymerization reaction is a frontal polymerization method.

10. The method for preparing hollow hydrogels by microfluidics-assisted frontal polymerization according to claim 1, characterized in that: The polymerization temperature initiated by the soldering iron is 100-120 °C, and the polymerization time initiated by the soldering iron is 40-60 s.