A method for rapidly solidifying microspheres based on a density gradient liquid column

Abstract

This invention relates to a method for rapidly preparing microspheres using a density gradient liquid column. The method combines pH-induced curing and extraction-heat curing, and incorporates a high-density buffer solution with a density similar to that of the microdroplets to construct a three-layer density gradient curing liquid column. The microdroplets rapidly solidify through the liquid column, solving problems such as long channels, cumbersome processes, and decreased sphericity due to microdroplet compression deformation in current microdroplet curing methods. Furthermore, the three layers of the density gradient curing column are miscible, avoiding heterogeneous shrinkage of the microdroplets at the interface, resulting in microspheres with high sphericity.

Description

Technical Field

[0001] This invention relates to a method for rapidly preparing microspheres based on density gradient liquid column solidification, belonging to the field of microsphere solidification. Background Technology

[0002] Microspheres are spherical particles with diameters in the nanometer and micrometer range. They possess excellent optical, electrical, mechanical, and other properties and are widely used in modern industrial production. They are also an important foundation for the development of future high-tech and emerging industries. Electronic information, biopharmaceuticals, energy, environment, and defense all rely on microspheres. With the rapid development of the 21st century, increasingly higher demands are being placed on microsphere preparation technology. These include the precision of nanometer and micrometer microsphere size, the uniformity of particle size distribution, the precise control of morphology and pore structure, as well as the control of material composition and surface functionalization. Due to the extremely complex preparation process of microsphere materials, for a long time, almost all high-performance, high-value-added microsphere materials in my country have been monopolized by foreign countries. For example, spacer microspheres, conductive gold microspheres, and light-diffusing microspheres used in liquid crystal displays are basically monopolized by Japan, while separation and purification media microspheres used in biopharmaceuticals and silica gel packing microspheres used in analytical chromatography columns are monopolized by Europe and the United States. With the increase in China's R&D investment, the speed of new product launches, and the intensification of market competition, a huge market and development opportunity has been opened up for high-performance domestically produced microsphere materials to replace imported microsphere materials, providing domestic manufacturers with new options to reduce costs and alleviate supply pressure.

[0003] Currently, there are many methods for preparing microspheres. Microemulsion polymerization involves dissolving monomer droplets in a continuous phase or within micelles to form swollen monomer micelles. Monomer continuously enters new micelles, forming new microspheres. Its advantage is relatively uniform particle size; its disadvantages include uncontrollable microsphere morphology, small particle size, and inability to encapsulate microspheres. The seeding method involves monomers within droplets continuously dissolving in the dispersed phase and being absorbed by swollen seed microspheres until swelling equilibrium is reached. After the swelling process, polymerization can proceed to obtain larger microspheres. Its advantage is uniform particle size; its disadvantages include inability to encapsulate active substances and a more complex preparation process. Microporous membrane emulsification uses precise pressure to force the dispersed phase through membrane pores into the continuous phase. At the membrane outlet, droplets gradually grow into droplets, which then detach from the membrane pores under the gentle flow field of the continuous phase, forming microdroplets. Further solidification yields microspheres. Its advantage is mild production conditions, without high temperature or high shear force; its disadvantages include non-uniform particle size (CV value around 15%), and the production process is not yet mature in China. Microfluidics prepares microdroplets with controllable particle size by strictly controlling the flow rates of two phases. Under the equilibrium of inertial forces, adhesive forces, and interfacial tension, the dispersed phase is periodically sheared by the continuous phase. Its advantages include uniform particle size (CV value can be less than 5%), low diffusivity, and low risk of cross-contamination; its disadvantages include high chip cost, susceptibility to clogging, difficulty in integration, and low yield.

[0004] The first step in microsphere production is the generation of microdroplets, and the second step is the solidification of microdroplets into microspheres. Currently, methods for solidifying microdroplets into microspheres include solvent evaporation, solvent extraction, and precipitation, but the most important is heat curing. This method uses heat to rapidly cross-link the microdroplets, achieving solidification. However, ordinary heat curing requires a long time to achieve the desired effect, necessitating sufficiently long fluid channels after microdroplet formation. The required length of the curing channel varies depending on the precursor, but is generally over 5 meters. The long channel and complex process can lead to insufficient gelation, resulting in overly soft gel particles that cannot support their own weight. When the gel particles contact the bottom of the container, they may not maintain their spherical shape and become flattened. Furthermore, microdroplets may stack and be compressed in the collection device, causing surface depressions on the final microspheres and a significant decrease in sphericity.

[0005] Therefore, developing a method for rapid solidification of microdroplets has become an urgent problem to be solved. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a method for rapidly preparing microspheres based on density gradient liquid column solidification.

[0007] The method of this invention combines pH-induced curing and extraction-heat curing, and constructs a three-layer density gradient curing column with a high-density buffer solution with a density similar to that of microdroplets. The microdroplets achieve rapid curing through the column, solving problems such as long channels, cumbersome processes, and decreased sphericity due to microdroplet compression deformation in current microdroplet curing methods. Furthermore, the three layers of the density gradient curing column are miscible, avoiding heterogeneous shrinkage of microdroplets at the interface, resulting in microspheres with high sphericity.

[0008] The technical solution of the present invention is as follows:

[0009] A method for rapidly preparing microspheres based on density gradient liquid column solidification includes the following steps:

[0010] (1) Preparation of density gradient liquid column: Add surfactant to organic alkane and stir to mix evenly to obtain upper layer solution; mix organic amine and solvent extractant and add surfactant, stir to mix evenly to obtain middle layer solution; stir and mix high density solvent, organic amine, solvent extractant and surfactant, and adjust density to obtain lower layer solution; put lower layer solution, middle layer solution and upper layer solution into container in sequence to obtain density gradient liquid column;

[0011] (2) Heat and keep the density gradient liquid column at a certain temperature, and let the microdroplets settle from the upper layer of the density gradient liquid column to the lower layer of the density gradient liquid column to complete the solidification and obtain microspheres.

[0012] According to a preferred embodiment of the present invention, in step (1), the organic alkane in the upper solution is tetradecane, and the surfactant is polydimethylsiloxane.

[0013] According to a preferred embodiment of the present invention, in step (1), the content of surfactant in the upper solution is 6-10 wt%.

[0014] According to a preferred embodiment of the present invention, in step (1), the organic amine in the intermediate layer solution is oleylamine, the solvent extractant is ethyl acetate, and the surfactant is polydimethylsiloxane.

[0015] According to a preferred embodiment of the present invention, in step (1), the mass content of organic amine in the intermediate layer solution is 3-5 wt%, and the mass content of surfactant is 6-10 wt%.

[0016] According to a preferred embodiment of the present invention, in step (1), the high-density solvent in the lower layer solution is carbon tetrachloride, the organic amine is oleylamine, the solvent extractant is ethyl acetate, and the surfactant is polydimethylsiloxane.

[0017] According to a preferred embodiment of the present invention, in step (1), the surfactant content in the lower layer solution is 6-10 wt%, the organic amine content is 5-8 wt%, and the controlled density is approximately 0.5-1.5 g / cm³. 3 .

[0018] According to a preferred embodiment of the present invention, in step (1), the mass ratio of organic amine to solvent extractant in the lower layer solution is 1:(6-8).

[0019] According to a preferred embodiment of the present invention, in step (1), the total height of the density gradient liquid column is 15-25 cm.

[0020] According to a preferred embodiment of the present invention, in step (1), the height ratio of the lower layer solution, the middle layer solution, and the upper layer solution is 2:4:3. During the fabrication of the density gradient liquid column, the solution is slowly injected using a dropper to avoid direct pouring which would cause mixing of the different liquid layers.

[0021] According to a preferred embodiment of the present invention, in step (2), the microdroplets are prepared by microfluidic method or membrane emulsification method, with tetradecane as the continuous phase and microsphere precursor as the dispersed phase.

[0022] According to a preferred embodiment of the present invention, in step (2), the density gradient liquid column is heated by water bath heating at a temperature of 55°C-65°C.

[0023] The technical features and superior effects of this invention are as follows:

[0024] 1. The density gradient liquid column of the present invention consists of three layers. The oil phase of the upper solution is used to prepare monodisperse microdroplets. The organic amine and solvent extractant in the middle solution play the roles of pH-induced solidification and extraction heating solidification. The high-density buffer solution in the lower solution reduces the compression between microdroplets after initial solidification, ensuring the sphericity of the solidified microspheres.

[0025] 2. In this invention, the three layers of the density gradient liquid column are all miscible, and the substrate avoids the heterogeneous shrinkage of microdroplets when they cross the interface, thus ensuring sphericity.

[0026] 3. This invention utilizes a combination of pH-induced curing and solvent extraction with heating curing to achieve initial curing by allowing microdroplets to settle from the top to the bottom layer. A short liquid column of approximately 20 cm is required for rapid curing. The curing method is simple to operate, requires minimal equipment, and produces microspheres with a sphericity greater than 99%. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the density gradient liquid column prepared in Example 1. 1 is the lower layer solution, 2 is the middle layer solution, and 3 is the upper layer solution.

[0028] Figure 2 This is an optical photograph of the monodisperse microdroplets prepared in step (2) of Example 1.

[0029] Figure 3 These are optical photographs of the microspheres obtained in Example 1 before (a) microdroplet curing and after (b) curing by density gradient liquid column.

[0030] Figure 4 This is an SEM image of silica microspheres obtained by washing and calcining the microspheres prepared in Example 1.

[0031] Figure 5 This is a SEM image of silica microspheres obtained by washing and calcining the microspheres prepared in Comparative Example 1.

[0032] Figure 6 This is an optical photograph of the monodisperse microdroplets prepared by the microfluidic method in Example 2.

[0033] Figure 7 This is an SEM image of silica microspheres obtained by washing and calcining the microspheres prepared in Example 2.

[0034] Figure 8 This is an optical photograph of the monodisperse microdroplets prepared by the membrane emulsification method in Experiment Example 3.

[0035] Figure 9 This is an SEM image of silica microspheres obtained by washing and calcining the microspheres prepared in Example 3.

[0036] Figure 10 This is a SEM image of silica microspheres obtained after washing and calcination of the microspheres prepared in Comparative Example 2.

[0037] Figure 11 This is a SEM image of silica microspheres obtained after washing and calcination of the microspheres prepared in Comparative Example 3. Detailed Implementation

[0038] To better understand the present invention, specific embodiments are described below.

[0039] Unless otherwise specified, the experimental methods used in the examples are conventional methods.

[0040] Unless otherwise specified, all materials and reagents used in the examples are commercially available.

[0041] Example 1

[0042] A method for rapidly preparing microspheres based on density gradient liquid column solidification includes the following steps:

[0043] (1) Fabrication of density gradient liquid column

[0044] Upper layer solution: Take a 500ml beaker, add 200g of tetradecane and 17.40g of polydimethylsiloxane, and mix with magnetic stirring for 30min;

[0045] Intermediate layer solution: Take a 200ml beaker, add 100g ethyl acetate, 5.75g oleylamine and 9.25g polydimethylsiloxane, and stir magnetically for 30min;

[0046] Lower layer solution: Take a 200ml beaker, add 8g oleylamine, 23g carbon tetrachloride, 60g ethyl acetate and 8g polydimethylsiloxane, and stir magnetically for 30min;

[0047] The lower, middle, and upper layers of solution were sequentially poured into a 30cm high glass liquid column to obtain a density gradient liquid column. The height of the lower layer was 4cm, the middle layer was 8cm, and the upper layer was 6cm, thus obtaining the density gradient liquid column required for solidification. Figure 1 As shown.

[0048] (2) Preparation of microdroplets

[0049] Silica microdroplets were prepared using a microfluidic method: Water, ethanol, tetraethyl orthosilicate (TEOS), and 1 mol / L hydrochloric acid solution were mixed in a mass ratio of 3:4:6:3, sealed, and stirred at room temperature for 4 hours to obtain a silica precursor solution. The silica precursor solution was used as the dispersed phase, with the upper layer solution in step (1) as the continuous phase. The flow rate ratio of the continuous phase to the dispersed phase was controlled at 6:1, so that the dispersed phase was periodically cut by the continuous phase, resulting in silica microdroplets with uniform particle size. Figure 2 As shown.

[0050] (3) The density gradient liquid column was heated at a constant temperature in a 60℃ water bath. The prepared microdroplets were introduced into the uppermost layer of the density gradient liquid column, 1 cm above the liquid surface, allowing them to settle freely within the column. It was observed that the microdroplets significantly decreased in size as they passed through the middle layer of the density gradient liquid column. Figure 3 As shown, when the microdroplets pass through the lower solution, the settling velocity slows down significantly, thereby reducing the compression and deformation between the microdroplets, completing solidification, and obtaining silica microspheres.

[0051] Comparative Example 1

[0052] The steps for preparing silica microspheres by heat curing are as follows:

[0053] (1) Preparation of microdroplets

[0054] Silica microdroplets were prepared using a microfluidic method: Water, ethanol, tetraethyl orthosilicate (TEOS), and 1 mol / L hydrochloric acid solution were mixed in a mass ratio of 3:4:6:3, sealed, and stirred at room temperature for 4 hours to obtain a silica precursor solution. The silica precursor solution was used as the dispersed phase, and the upper layer solution in step (1) of Example 1 was used as the continuous phase. The flow rate ratio of the continuous phase to the dispersed phase was controlled at 6:1, so that the dispersed phase was periodically cut by the continuous phase, resulting in silica microdroplets with uniform particle size. Figure 2 As shown.

[0055] (2) The silica microdroplets were heated to 60°C in the upper solution of step (1) in Example 1 to solidify them, and silica microspheres were obtained.

[0056] Experimental Example

[0057] The microspheres obtained in Example 1 and Comparative Example 1 were washed three times with acetone, and then calcined at 600°C for 4 hours. The calcined silica microspheres were then scanned by electron microscopy. The electron micrograph of the silica microspheres obtained in Example 1 is shown below. Figure 4 As shown, the electron micrograph of the silica microspheres obtained in Comparative Example 1 is as follows. Figure 5 As shown in the comparison, it can be seen that the surface of the microspheres cured by density gradient in Example 1 is smooth and without depressions, and the obtained microspheres have high sphericity.

[0058] Example 2

[0059] The method for preparing microspheres based on rapid solidification of a density gradient liquid column as described in Example 1 differs in that:

[0060] By replacing the microfluidic chip in step (2) of microdroplet preparation with a chip with a small shear diameter (existing technology), and adjusting the flow rate ratio of the continuous phase to the dispersed phase to 10:1, the resulting silica microdroplets are as follows: Figure 6 As shown, from Figure 6 It can be seen that the microdroplet size is significantly smaller than that in Example 1, and other steps and parameters are performed as in Example 1.

[0061] The microspheres obtained in Example 2 were washed three times with acetone, and then calcined at 600°C for 4 hours. The calcined silica microspheres were then subjected to electron microscopy, and the resulting electron microscopy images are shown below. Figure 7 As shown, compared with the silica microspheres of Example 1, the particle size is significantly reduced, but the surface of the microspheres is still relatively smooth and the sphericity is high.

[0062] Example 3

[0063] The method for preparing microspheres based on rapid solidification of a density gradient liquid column as described in Example 1 differs in that:

[0064] Replace step (2) with:

[0065] Silica microdroplets were prepared using a microporous membrane emulsification method: Water, ethanol, tetraethyl silicate (TEOS), and 1 mol / L hydrochloric acid solution were mixed in a mass ratio of 8:4:5:8, sealed, and stirred at room temperature for 4 hours to obtain a silica precursor solution. The silica precursor solution was used as the dispersed phase. In step (1) of Example 1, the upper solution was the continuous phase. Under pressure, the dispersed phase permeated through micropores into the continuous phase, gradually growing into microdroplets at the micropores. Under the gentle flow field of the continuous phase, the droplets detached from the micropores to obtain silica microdroplets. Figure 8 As shown, other steps and parameters are performed according to Example 1.

[0066] The microspheres obtained in Example 3 were washed three times with acetone, and then calcined at 600°C for 4 hours. The calcined silica microspheres were then scanned by electron microscopy, and the resulting electron micrographs are shown below. Figure 9 As shown, from Figure 9 It can be seen that monodisperse silica microspheres have a wide particle size distribution, a large CV value, and high sphericity.

[0067] Example 4

[0068] The method for preparing microspheres based on rapid solidification of a density gradient liquid column as described in Example 1 differs in that:

[0069] Replace step (2) with:

[0070] Alumina microdroplets were prepared using a microfluidic method: 10 g of deionized water (85 °C) was added to a beaker containing 1.2 g of aluminum tri-tert-butoxide (ATSB), the beaker was sealed to prevent evaporation, and the mixture was stirred at 300 rpm for 30 minutes in an 85 °C water bath. Then, the hydrolysis product, sec-butanol, and excess water were evaporated in a 90 °C water bath until the concentration of the hydrolysis product reached 7.5 wt%. Next, a 10% nitric acid solution was added dropwise to the beaker until the pH reached 2-3. Finally, the prepared mixture was stirred at 400 rpm for 1 hour at room temperature to obtain a clear sol. The resulting aluminum sol was used as the dispersed phase, and the upper layer of the density gradient solution was used as the continuous phase. The flow rate ratio of the continuous phase to the dispersed phase was controlled at 6:1, allowing the dispersed phase to be periodically cut by the continuous phase, resulting in alumina microdroplets with uniform particle size.

[0071] Other steps and parameters were performed as in Example 1, and the resulting alumina microspheres had uniform particle size and high sphericity.

[0072] Comparative Example 2

[0073] The method for preparing microspheres based on rapid solidification of a density gradient liquid column as described in Example 1 differs in that:

[0074] The heights of the liquid columns in the lower, middle, and upper layers were varied; the height of the liquid column in the lower layer was 4 cm, the height of the liquid column in the middle layer was 4 cm, and the height of the liquid column in the upper layer was 6 cm. Other steps and parameters were performed as in Example 1.

[0075] The microspheres obtained in Comparative Example 2 were washed three times with acetone, and then calcined at 600℃ for 4 hours. The calcined silica microspheres were then subjected to scanning electron microscopy (SEM). The SEM images of the obtained silica microspheres are shown below. Figure 10 As shown, from Figure 10 It can be seen that due to the short curing time, the microdroplets piled up together before they were fully cured, causing them to press against each other, resulting in slight depressions on the surface of the microspheres and a decrease in sphericity.

[0076] Comparative Example 3

[0077] The method for preparing microspheres based on rapid solidification of a density gradient liquid column as described in Example 1 differs in that:

[0078] The composition of the density gradient liquid column was changed by removing the lower layer solution. The height of the upper layer solution column was 6 cm, and the height of the middle layer solution column was 8 cm. Other steps and parameters were performed as in Example 1.

[0079] The microspheres obtained in Comparative Example 3 were washed three times with acetone, and then calcined at 600℃ for 4 hours. The calcined silica microspheres were then subjected to electron microscopy, and the resulting electron micrographs are shown below. Figure 11 As shown, from Figure 11 It can be seen that, due to the lack of a high-density buffer layer, the mutual compression between microspheres cannot be reduced, resulting in obvious compression marks on the surface of the microspheres and a decrease in sphericity.

Claims

1. A method for preparing microspheres by quick solidification based on a density gradient liquid column, comprising the following steps: (1) preparing a density gradient liquid column: adding a surfactant to an organic alkane, stirring and mixing uniformly to obtain an upper solution; mixing an organic amine and a solvent extractant and adding a surfactant, stirring and mixing uniformly to obtain a middle solution; stirring and mixing a high-density solvent, the organic amine, the solvent extractant and the surfactant, and adjusting the density to obtain a lower solution; sequentially loading the lower solution, the middle solution and the upper solution into a container to obtain the density gradient liquid column; the organic alkane in the upper solution is tetradecane, and the surfactant is polydimethylsiloxane, and the content of the surfactant in the upper solution is 6-10 wt%; in the preparation of the middle solution, the organic amine is oleylamine, the solvent extractant is ethyl acetate, and the surfactant is polydimethylsiloxane, and the mass content of the organic amine in the middle solution is 3-5 wt%, and the mass content of the surfactant is 6-10 wt%; in the preparation of the lower solution, the high-density solvent is carbon tetrachloride, the organic amine is oleylamine, the solvent extractant is ethyl acetate, and the surfactant is polydimethylsiloxane; (2) heating and keeping the density gradient liquid column, and allowing microdroplets to settle from the upper solution at the uppermost layer of the density gradient liquid column to the lower solution at the lowermost layer, completing solidification, and obtaining microspheres; the microdroplets are prepared by microfluidic method or membrane emulsification method, the continuous phase is tetradecane, and the dispersed phase is a precursor of the microspheres.

2. The method of claim 1, wherein, The mass content of the surfactant in the lower layer solution is 6-10 wt%, the mass content of the organic amine is 5-8 wt%, and the regulated density is 0.5-1.5 g / cm 3 .

3. The method of claim 1, wherein, In step (1), the mass ratio of the organic amine to the solvent extractant in the lower solution is 1: (6-8).

4. The method of claim 1, wherein, In step (1), the total liquid column height of the density gradient liquid column is 15-25 cm.

5. The method of claim 1, wherein, In step (1), the height ratio of the lower solution, the middle solution and the upper solution is 2:4:

3.

6. The method of claim 1, wherein, In step (2), the heating of the density gradient liquid column is by water bath heating, and the heating temperature is 55-65℃.

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