Core-shell type silicon dioxide chromatographic microsphere and preparation method thereof

Abstract

The invention provides a core-shell type silicon dioxide chromatographic microsphere and a preparation method thereof. The preparation method comprises the following steps: 1) preparing solid silicon dioxide microspheres; 2) coating silicon dioxide microspheres with template agent micelles; (3) preparing composite silicon dioxide core-shell microspheres; (4) preparing silicon dioxide core-shell microspheres; and thus, the core-shell type silicon dioxide chromatographic microspheres are obtained. The core of the prepared core-shell chromatographic microsphere is a solid silicon dioxide microsphere, the particle size can be controlled to be 1.5-3 microns, the core-shell chromatographic microsphere has good monodispersity, the shell layer is a silicon dioxide shell layer with a pore structure and controllable thickness, the pore diameter can reach about 10 nm, the shell layer thickness can be controlled to be 350-550 nm, and the core-shell chromatographic microsphere is suitable for chromatographic separation of organic macromolecules.

Description

Technical Field

[0001] This invention relates to the field of chromatographic separation packing technology, and in particular to a method for preparing core-shell silica chromatographic microspheres. Background Technology

[0002] High-performance liquid chromatography (HPLC) offers advantages such as high efficiency, speed, and ease of operation in separation and analysis, and is widely used in food safety testing, environmental monitoring, production process control, and protein separation and purification. The core of an HPLC system is the chromatographic column, whose performance directly determines the separation effect. Therefore, the preparation and optimization of column packing materials are crucial for the development of chromatographic technology. Compared to non-porous silica spheres of the same particle size, core-shell microspheres with porous shells have a larger specific surface area. The porous shell design allows solutes to enter more easily and interact with the packing surface, achieving efficient chromatographic separation and improving column efficiency and resolution. Compared to fully porous microspheres, the solid core and porous shell structure increases the mechanical stability of the packing material while improving the permeability and thermal conductivity of the chromatographic bed. The solid core also reduces the dispersion path of the solute within the packing material, further contributing to improved chromatographic separation efficiency. The preparation of core-shell microspheres with porous shells involves at least two steps: first, preparing a solid silica core with good monodispersity; and then coating the core surface with a porous shell. Existing methods for preparing core-shell microspheres include spray drying, polymerization-induced colloidal aggregation, layer-by-layer self-assembly, and template methods. These methods have some drawbacks that cannot be overcome in the short term. Core-shell microspheres prepared by spray drying have a wide particle size distribution. During the preparation process of polymerization-induced colloidal aggregation, agglomeration, uneven coating, and secondary nucleation are prone to occur. Layer-by-layer self-assembly requires multiple coating and cleaning processes, which is time-consuming and labor-intensive.

[0003] There are currently many reports on chromatographic packing materials, including numerous patents concerning the preparation of core-shell silica microspheres, such as the following:

[0004] Patent application number 202211703874.4 discloses a method for preparing monodisperse silica core-shell microspheres using a dual-template approach. However, this method involves a complicated and uncontrollable preparation process, requiring the preparation of the core based on purchased template microspheres. Furthermore, the prepared core is not a solid silica microsphere and still has micropores, which can easily create dead zones during solute flow.

[0005] Patent application number 201811589409.6 discloses a core-shell structured silica microsphere and its preparation method. The method involves mixing nano-silica with additives and pressing it into a block, removing the additives by high-temperature calcination, and then immersing the high-temperature calcined block in high-melting-point lava to clean it and obtain core-shell structured silica microspheres. During the entire preparation process, the silica microspheres exist as mutually adhered blocks, and the reaction process is uneven. Therefore, the prepared core-shell microspheres are severely adhered and the shell coating is extremely uneven.

[0006] Patent application number 202110772393.8 discloses a method for preparing nano-core-shell silica microspheres. The method involves coating a layer of silica under alkaline conditions and then performing a second coating under acidic conditions to form a dense silica layer. After the two coatings, the shell layer is only 33 nm thick at most. The shell layer is relatively thin and has low porosity, which limits the sample carrying capacity of the microspheres. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a core-shell type silica microsphere (chromatographic microsphere) and its preparation method.

[0008] To address the above problems, this invention provides a method for preparing core-shell silica microspheres (chromatographic microspheres), comprising the following steps:

[0009] 1) Preparation of solid silica microspheres;

[0010] 2) Template agent micelles coated with silica microspheres;

[0011] 3) Preparation of composite silica core-shell microspheres;

[0012] 4) Preparation of silica core-shell microspheres:

[0013] This yields core-shell silica microspheres (chromatographic microspheres).

[0014] An improvement to the preparation method of the core-shell silica microspheres (chromatographic microspheres) of the present invention includes the following steps:

[0015] 1) Preparation of solid silica microspheres:

[0016] Preparation of solution A: Solution A consists of a catalyst, an electrolyte, and a solvent. The volume content of the catalyst in solution A is 4% to 10% (preferably 5% to 8.5%), and the concentration of the electrolyte in solution A is 4.0 to 8.0 mmol / L (preferably 4 to 6.6 mmol / L).

[0017] Preparation of solution B: Solution B is composed of tetraethyl orthosilicate and anhydrous ethanol; the volume content of tetraethyl orthosilicate in solution B is 10% to 20% (preferably 15% to 20%);

[0018] Under low-speed stirring (stirring speed of 60-300 rpm), solution B is slowly added dropwise to solution A and the reaction is carried out at room temperature (dropping time is 3-10 hours). After the dropwise addition is completed, low-speed stirring is continued for 5-15 hours (preferably 5-10 hours). The precipitate produced by the reaction is solid silica microspheres (solid silica microspheres with good monodispersity, serving as the core).

[0019] The volume ratio (V:V) of solution A to solution B is 1.0 to 1.2:1.

[0020] Solution A provides the environment required for microsphere growth, and solution B provides the silicon source required for microsphere growth, thus producing well-dispersed solid silica microspheres as the core;

[0021] 2) Template agent micelles coated with silica microspheres:

[0022] Using cationic surfactants as template agents;

[0023] Solid silica microspheres and a template agent are uniformly dispersed in an alcohol-water solution and stirred at room temperature (stirring speed 300-800 rpm) for 0.5-2 h (preferably 0.5-1 h) to obtain a silica microsphere dispersion coated with template agent micelles (hereinafter referred to as dispersion); the weight ratio of solid silica microspheres to template agent is 1:5-10.

[0024] Explanation: Cationic surfactants form positively charged micelles in solution. These positively charged micelles adsorb onto the surface of solid silica microspheres, thus preparing silica microspheres coated with template agent micelles.

[0025] 3) Preparation of composite silica core-shell microspheres:

[0026] First, a catalyst is added to the silica microsphere dispersion coated with template agent micelles obtained in step 2). Under stirring conditions, a silicon source is then added intermittently (intermittent addition time is 1-8 hours, preferably in 4 additions with an interval of 1-2 hours between each addition, so as to achieve uniform dispersion of silicon source and slow growth of shell layer on the surface of silica microspheres coated with template agent micelles). After the silicon source is added, the reaction is carried out at room temperature (stirring speed 300-800 rpm) for 10-15 hours; thus obtaining silica core-shell microspheres with composite template agent.

[0027] The silicon source is a tetraethyl orthosilicate ethanol solution, wherein the volume content of tetraethyl orthosilicate in the tetraethyl orthosilicate ethanol solution is 1.0% to 5.0% (preferably 2% to 5%).

[0028] For every 0.1 g of solid silica microspheres, a dispersion of silica microspheres coated with template micelles is prepared with 0.5–1 mL of catalyst (ammonia).

[0029] For every 0.1 g of solid silica microspheres, the template agent micelle-coated silica microsphere dispersion is prepared with 0.4–1 mL of tetraethyl orthosilicate.

[0030] 4) Preparation of silica core-shell microspheres:

[0031] The silica core-shell microspheres with composite template agent obtained in step 3) were dispersed in hydrochloric acid solution (0.1±0.02M hydrochloric acid solution), sealed in a hydrothermal reactor for hydrothermal pore expansion, then washed and dried, and then calcined at high temperature (in a muffle furnace) to remove the template agent, thus obtaining core-shell silica microspheres (chromatographic microspheres).

[0032] The temperature of the hydrothermal pore-expanding reaction is 80-200℃, and the reaction time is 12-48h (preferably 24h at 100-120℃).

[0033] The high-temperature calcination is carried out at 500-700℃ for 6-10 hours (preferably calcined at 550-650℃ for 6-10 hours).

[0034] As a further improvement to the preparation method of the present invention, the catalysts in steps 1) and 3) are at least any one of the following (i.e., a combination of one or more): sodium hydroxide, sodium carbonate, ammonia, triethylamine, diethylamine, and triethanolamine.

[0035] Note: The catalysts used in steps 1) and 3) can be the same or different.

[0036] As a further improvement to the preparation method of the present invention, in step 1):

[0037] The electrolytes are sodium chloride, potassium chloride, and lithium chloride;

[0038] The solvent consists of deionized water and anhydrous ethanol; the volume ratio of deionized water to anhydrous ethanol is 1:6 to 8.

[0039] As a further improvement to the preparation method of the present invention, in step 2):

[0040] The cationic surfactant used as a template agent is at least one of the following (i.e., a combination of one or more): octadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide (CTAB), hexadecyltrimethylammonium chloride (CTAC), methyltrioctylammonium bromide, and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer (P123).

[0041] When multiple template agents are selected, the mass ratio between them is generally 1:1.

[0042] As a further improvement to the preparation method of the present invention, in step 2):

[0043] The alcohol-water solution is obtained by mixing ethanol and water in a volume ratio of 1:(1±0.1).

[0044] Each 0.1g of solid silica microspheres is mixed with 40-100ml of alcohol-water solution.

[0045] As a further improvement to the preparation method of the present invention, in step 4):

[0046] For every 0.1 g of solid silica microspheres, the corresponding silica core-shell microspheres of the composite template agent are prepared with 10–50 mL of (0.1 ± 0.02) M hydrochloric acid solution.

[0047] The cleaning and drying process involves washing with water and ethanol alternately until the pH is neutral, followed by drying at 60±10℃ for 240±20 minutes.

[0048] As a further improvement to the preparation method of the present invention, in step 4):

[0049] After hydrothermal pore expansion, the temperature is increased to the required high-temperature calcination temperature at a heating rate of 1℃ / min.

[0050] The present invention also provides core-shell silica microspheres (chromatographic microspheres) prepared using any of the above methods.

[0051] This invention provides a core-shell silica chromatographic microsphere and its preparation method. The core of the core-shell chromatographic microsphere prepared by this invention is a solid silica microsphere with a particle size controllable between 1.5 and 3 μm and good monodispersity. The shell is a silica shell with a pore structure and controllable thickness, with a pore size of about 10 nm and a shell thickness controllable between 350 and 550 nm.

[0052] Compared with the prior art, the present invention has the following beneficial effects:

[0053] The silica microspheres prepared by the method of this invention have solid cores, thus ensuring stable mechanical strength, good monodispersity, and no agglomeration. The size of the silica microsphere cores can be controlled by the process parameters set in this invention (e.g., adjusting the amount of electrolyte added), thereby controlling the overall size of the core-shell microspheres. The shell thickness and pore structure of the microspheres can be controlled by the process parameters set in this invention. We know that the pore structure (e.g., pore size and porosity) of the microsphere shell is crucial to separation performance; the size and distribution of the pores affect the residence time and separation mechanism of molecules in the microspheres. Therefore, this invention achieves selective separation of different molecules by adjusting the pore size. The preparation process of this method is stable, has good repeatability, and is suitable for mass production.

[0054] In summary, this invention utilizes a specific method to prepare large-particle-size solid silica microspheres with a particle size of 1.5–3 μm as the core, and cationic surfactants as composite template agents, which are adsorbed onto the surface of the core in the form of micelles. A silicon source and catalyst are then added; after hydrolysis and condensation of the silicon source, silica particles are generated and deposited on the silicon core, forming a shell structure. The composite template agent is then removed through hydrothermal pore expansion and high-temperature calcination, yielding core-shell silica chromatographic microspheres. The core-shell silica chromatographic microspheres prepared by this invention exhibit good monodispersity, no aggregation, adjustable pore structure (shell pore size), and uniform shell thickness, which can be controlled within the range of 350–550 nm, making them suitable for the chromatographic separation of organic macromolecules. Attached Figure Description

[0055] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0056] Figure 1 A transmission electron microscope (TEM) image of a monodisperse silica microsphere provided in Example 1; according to this... Figure 1 It can be determined that the microspheres have a core-shell structure with a shell thickness of approximately 557 nm.

[0057] Figure 2 This is a transmission electron microscope (TEM) image of a monodisperse silica microsphere provided in Example 2; according to this... Figure 2 It can be determined that the microspheres have a core-shell structure, with a shell thickness of approximately 447 nm, and the shell is relatively... Figure 1 The pore structure is more obvious, and the N2 isothermal adsorption-desorption results also prove that the microspheres in Example 2 have larger pore sizes.

[0058] Figure 3 This is a transmission electron microscope (TEM) image of a monodisperse silica microsphere provided in Example 3; according to this... Figure 3 It can be seen that the microspheres have a core-shell structure with a shell thickness of about 368 nm and obvious pores in the shell. Detailed Implementation

[0059] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto:

[0060] In this invention, the concentration of ammonia water is 28% (mass%).

[0061] After hydrothermal pore expansion, the temperature is increased to the required high-temperature calcination temperature at a heating rate of 1℃ / min.

[0062] Example 1: A method for preparing core-shell silica chromatographic microspheres, comprising the following steps:

[0063] 1) Preparation of solid silica microspheres:

[0064] Preparation of Solution A: Solution A consists of 3 ml of ammonia water as a catalyst, 0.2 mmol (approximately 0.015 g) of potassium chloride as an electrolyte, and a solvent obtained by mixing 6 mL of deionized water and 38 mL of anhydrous ethanol. Therefore, the volume content of the catalyst in Solution A is approximately 6.4%, and the concentration of the electrolyte in Solution A is approximately 4.25 mmol / L.

[0065] Preparation of Solution B: Solution B consists of 6.5 mL of tetraethyl orthosilicate and 35 mL of anhydrous ethanol; the volume content of tetraethyl orthosilicate in Solution B is 15.6%;

[0066] Under low-speed stirring (stirring speed of 60-300 rpm), solution B was slowly added dropwise to solution A at a rate of 0.2 mL / min using a peristaltic pump for the reaction. That is, the addition time was about 208 minutes (about 3.46 h). After the addition of solution B was completed, low-speed stirring was continued for 5 h.

[0067] The mixture was then filtered, and the precipitate produced by the reaction was taken and air-dried in a conventional manner. It was named solid silica microspheres (solid silica microspheres with good monodispersity were used as the core).

[0068] Solution A: Solution B ≈ 1.13:1 (V:V).

[0069] 2) Template agent micelles coated with silica microspheres:

[0070] 0.1 g of solid silica microspheres and 0.5 g of hexadecyltrimethylammonium chloride (as a template agent) were uniformly dispersed in 100 ml of alcohol-water solution and reacted magnetically at 500 rpm for 30 min at room temperature to obtain a silica microsphere dispersion coated with template agent micelles (hereinafter referred to as dispersion).

[0071] The alcohol-water solution is obtained by mixing ethanol and water in a volume ratio of 1:1.

[0072] 3) Preparation of composite silica core-shell microspheres:

[0073] 1 mL of ammonia was added to the dispersion first, and then 20 mL of tetraethyl orthosilicate ethanol solution (containing 0.4 mL of tetraethyl orthosilicate) was added intermittently at 500 rpm. The addition was done in four equal portions with an interval of 1 hour between each portion. After all the additions were completed, the reaction was stirred for another 10 hours to allow the shell to grow slowly (the silica core-shell microspheres formed a shell-encapsulated morphology). Silica core-shell microspheres with composite template agent were obtained.

[0074] 4) Preparation of silica core-shell microspheres:

[0075] The silica core-shell microspheres with composite template agent obtained in step 3) were dispersed in 50 mL of 0.1 M hydrochloric acid solution, sealed in a hydrothermal reactor, and hydrothermally expanded at 100 °C for 24 h. After cooling to room temperature, they were washed and dried (water and ethanol were alternated until the pH of the washing solution was neutral, and then dried at 60 °C for 240 min). The template agent was removed by calcination at 550 °C for 6 h in a muffle furnace, thus obtaining core-shell silica chromatographic microspheres.

[0076] Example 2: A method for preparing core-shell silica chromatographic microspheres, comprising the following steps:

[0077] 1) Preparation of solid silica microspheres;

[0078] Preparation of solution A: Solution A is composed of a solvent obtained by mixing 8 mL of ammonia water as a catalyst, 0.54 mmol (about 0.04 g) of potassium chloride as an electrolyte, 12 mL of deionized water, and 76 mL of anhydrous ethanol. Therefore, the volume content of the catalyst in solution A is about 8.3%, and the concentration of the electrolyte in solution A is about 5.62 mmol / L.

[0079] Preparation of Solution B: Solution B consists of 13 mL of tetraethyl orthosilicate and 70 mL of anhydrous ethanol; the volume content of tetraethyl orthosilicate in Solution B is approximately 15.6%;

[0080] Under low-speed stirring conditions, solution B was slowly added dropwise to solution A at a rate of 0.3 mL / min using a peristaltic pump for the reaction. That is, the addition time was about 276 minutes (about 4.611 h). After the addition of solution B was completed, low-speed stirring was continued for 8 h.

[0081] The mixture was then filtered, and the precipitate produced by the reaction was taken and air-dried in a conventional manner. It was named solid silica microspheres (solid silica microspheres with good monodispersity were used as the core).

[0082] Solution A: Solution B ≈ 1.16:1 (V:V).

[0083] 2) Template agent micelles coated with silica microspheres:

[0084] 0.2 g of solid silica microspheres, 1.0 g of hexadecyltrimethylammonium chloride and 1.0 g of methyltrioctylammonium bromide (as template agent) were uniformly dispersed in 160 ml of alcohol-water solution and magnetically stirred at 500 rpm for 30 min at room temperature to obtain a silica microsphere dispersion coated with template agent micelles (hereinafter referred to as dispersion).

[0085] The alcohol-water solution is obtained by mixing ethanol and water in a volume ratio of 1:1.

[0086] 3) Preparation of composite silica core-shell microspheres:

[0087] 2 mL of ammonia was first added to the dispersion, and then 40 mL of tetraethyl orthosilicate ethanol solution (containing 0.8 mL of tetraethyl orthosilicate) was added intermittently while stirring at 500 rpm. The solution was added evenly in four portions, with an interval of 1 hour between each addition. After all the solution was added, the reaction was continued for 10 hours to allow the shell to grow slowly (the silica core-shell microspheres formed a shell-encapsulated morphology) to obtain silica core-shell microspheres with a composite template agent.

[0088] 4) Preparation of silica core-shell microspheres:

[0089] The silica core-shell microspheres with composite template agent obtained in step 3) were dispersed in 80 ml of 0.1 M hydrochloric acid solution, sealed in a hydrothermal reactor, and hydrothermally expanded at 100 °C for 24 h. After cooling to room temperature, they were washed and dried (alternating water and ethanol until the pH of the washing solution was neutral, and then dried at 60 °C for 240 min). The template agent was removed by calcination at 550 °C for 6 h in a muffle furnace, thus obtaining core-shell silica chromatographic microspheres.

[0090] Example 3: A method for preparing core-shell silica chromatographic microspheres, comprising the following steps:

[0091] 1) Preparation of solid silica microspheres;

[0092] Preparation of Solution A: Solution A is composed of a solvent obtained by mixing 28 mL of ammonia water as a catalyst, 3.49 mmol (about 0.26 g) of potassium chloride as an electrolyte, 58 mL of deionized water, and 440 mL of anhydrous ethanol. Therefore, the volume content of the catalyst in Solution A is about 5.3%, and the concentration of the electrolyte in Solution A is 6.58 mmol / L.

[0093] Preparation of Solution B: Solution B consists of 100 mL of tetraethyl orthosilicate and 420 mL of anhydrous ethanol; the volume content of tetraethyl orthosilicate in Solution B is 19.2%.

[0094] Under low-speed stirring conditions, solution B was slowly added dropwise to solution A at a rate of 1.0 mL / min using a peristaltic pump for the reaction. That is, the addition time was about 520 minutes (about 8.66 h). After the addition of solution B was completed, low-speed stirring was continued for 10 h.

[0095] The mixture was then filtered, and the precipitate produced by the reaction was taken and air-dried in a conventional manner. It was named solid silica microspheres (solid silica microspheres with good monodispersity were used as the core).

[0096] Solution A : Solution B = 1.01 : 1 (V : V),

[0097] 2) Template agent micelles coated with silica microspheres:

[0098] 2.0 g of solid silica microspheres, 5.0 g of hexadecyltrimethylammonium chloride and 5.0 g of P123 (as a template agent) were uniformly dispersed in 800 ml of alcohol-water solution and magnetically stirred at 800 rpm for 60 min at room temperature to obtain a silica microsphere dispersion coated with template agent micelles (hereinafter referred to as dispersion).

[0099] The alcohol-water solution is obtained by mixing ethanol and water in a volume ratio of 1:1.

[0100] 3) Preparation of composite silica core-shell microspheres:

[0101] First, add 10 mL of ammonia water to the dispersion and stir at 500 rpm. Then, intermittently add 400 mL of tetraethyl orthosilicate ethanol solution (containing 20 mL of tetraethyl orthosilicate). Add the solution evenly in four portions, with an interval of 2 hours between each addition. After all the solution has been added, continue stirring and reacting for 15 hours to allow the shell layer to grow slowly (forming a shell-coated morphology of silica core-shell microspheres). Silica core-shell microspheres with a composite template agent are obtained.

[0102] 4) Preparation of silica core-shell microspheres:

[0103] The silica core-shell microspheres with composite template agent obtained in step 3) were dispersed in 200 ml of 0.1 M hydrochloric acid solution, sealed in a hydrothermal reactor, and hydrothermally expanded at 120 °C for 24 h. After cooling to room temperature, they were washed and dried (alternating water and ethanol until the pH of the washing solution was neutral, and then dried at 60 °C for 240 min). The template agent was removed by calcination at 650 °C for 10 h in a muffle furnace, thus obtaining core-shell silica chromatographic microspheres.

[0104] The core-shell silica chromatographic microspheres obtained in Examples 1 to 3 were analyzed using the conventional N2 isothermal adsorption-desorption method. The results are shown in Table 1 below:

[0105] Table 1

[0106]

[0107] Note: The TEM image shows that the core has no pores and is a solid microsphere.

[0108] Comparative Example 1: The use of "8 ml of ammonia water as a catalyst" in step 1) of Example 2 was omitted, and the rest was the same as in Example 1.

[0109] The results showed that microspheres could not be synthesized in this system without the catalytic effect of a catalyst.

[0110] Comparative Example 2: The amount of "ammonia water as catalyst" in step 1) of Example 2 was changed from "8 ml" to "16 ml", and the rest was the same as in Example 2.

[0111] The results showed that the microspheres had varying particle sizes, severe adhesion, poor monodispersity, and D90 / D10 = 5.2.

[0112] Comparative Example 3: The use of "0.54 mmol (about 0.04 g) of potassium chloride as an electrolyte" in step 1) of Example 2 was omitted, and the rest was the same as in Example 2.

[0113] The results showed that the synthesized microspheres were nanoscale microspheres with a particle size of less than 500 nm, which did not meet the size requirements of core-shell microspheres for the core.

[0114] Comparative Example 4: The amount of potassium chloride as electrolyte in step 1) of Example 2 was changed from "0.54 mmol" to "0.96 mmol", and the rest was the same as in Example 2.

[0115] The results showed that the microspheres had varying sizes, severe adhesion, poor monodispersity, and D90 / D10 = 6.8.

[0116] Comparative Example 5: The template agent “1.0g hexadecyltrimethylammonium chloride and 1.0g methyltrioctylammonium bromide” in step 2) of Example 2 was replaced with “2.0g polyethylene glycol 2000 (conventional template agent)”, and the rest was the same as in Example 2.

[0117] The result was: a shell structure could not be formed.

[0118] Comparative Example 6: In step 3) of Example 2, "intermittently add 40 mL of tetraethyl orthosilicate ethanol solution" was changed to "add 40 mL of tetraethyl orthosilicate ethanol solution all at once"; the rest was the same as in Example 2.

[0119] The results showed that the microsphere shell thickness was uneven and the sphericity was poor.

[0120] Comparative Example 7: In step 4) of Example 2, the phrase "the obtained composite template agent silica core-shell microspheres are dispersed in 80 ml of 0.1 M hydrochloric acid solution" was changed to "the obtained composite template agent silica core-shell microspheres are dispersed in 80 ml of deionized water", and the rest was the same as in Example 2.

[0121] The results showed that the pore size of the microsphere shell was less than 2 nm, which could not meet the pore size requirements of chromatographic microspheres.

[0122] Comparative Example 8: In step 3) of Example 2, "hydrothermal expansion at 100°C for 24 hours" is changed to "hydrothermal expansion at 250°C for 24 hours", and the rest is the same as in Example 2.

[0123] The results showed that the microsphere shell was severely etched, resulting in hollow areas and reduced mechanical strength.

[0124] Finally, it should be noted that the above examples are merely some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments and many variations are possible. All variations that can be directly derived or conceived by those skilled in the art from the disclosure of the present invention should be considered within the scope of protection of the present invention.

Claims

1. A method for preparing core-shell silica microspheres, characterized in that... Includes the following steps: 1) Preparation of solid silica microspheres; 2) Template agent micelles coated with silica microspheres; 3) Preparation of composite silica core-shell microspheres; 4) Preparation of silica core-shell microspheres: This yields core-shell silica microspheres.

2. The method for preparing core-shell silica microspheres according to claim 1, characterized in that: 1) Preparation of solid silica microspheres: Preparation of solution A: Solution A consists of a catalyst, an electrolyte, and a solvent. The volume content of the catalyst in solution A is 4% to 10%, and the concentration of the electrolyte in solution A is 4.0 to 8.0 mmol / L. Preparation of solution B: Solution B is composed of tetraethyl orthosilicate and anhydrous ethanol; the volume content of tetraethyl orthosilicate in solution B is 10% to 20%; Under low-speed stirring conditions, solution B was slowly added dropwise to solution A and the reaction was carried out at room temperature. After the addition was completed, low-speed stirring was continued for 5 to 15 hours. The precipitate produced by the reaction was solid silica microspheres. The volume ratio of solution A to solution B is 1.0 to 1.2 to 1.

1. 2) Template agent micelles coated with silica microspheres: Using cationic surfactants as template agents; Solid silica microspheres and template agent are uniformly dispersed in an alcohol-water solution and stirred at room temperature for 0.5-2 hours to obtain a silica microsphere dispersion coated with template agent micelles; the weight ratio of solid silica microspheres to template agent is 1:5-10. 3) Preparation of composite silica core-shell microspheres: First, add a catalyst to the silica microsphere dispersion coated with template agent micelles obtained in step 2), and then add a silicon source intermittently under stirring conditions. After the silicon source is added, stir and react at room temperature for 10 to 15 hours to obtain silica core-shell microspheres with composite template agent. The silicon source is a tetraethyl orthosilicate ethanol solution, wherein the volume content of tetraethyl orthosilicate in the tetraethyl orthosilicate ethanol solution is 1.0% to 5.0%; For every 0.1 g of solid silica microspheres, a dispersion of silica microspheres coated with template micelles is prepared with 0.5–1 mL of catalyst. For every 0.1 g of solid silica microspheres, the template agent micelle-coated silica microsphere dispersion is prepared with 0.4–1 mL of tetraethyl orthosilicate. 4) Preparation of silica core-shell microspheres: The silica core-shell microspheres with composite template agent obtained in step 3) are dispersed in hydrochloric acid solution, sealed in a hydrothermal reactor for hydrothermal pore expansion, then washed and dried, and then calcined at high temperature to remove the template agent to obtain core-shell silica microspheres. The temperature of the hydrothermal pore-expanding reaction is 80–200℃, and the reaction time is 12–48 h; The high-temperature calcination is performed at 500–700℃ for 6–10 hours.

3. The method for preparing core-shell silica microspheres according to claim 2, characterized in that... The catalysts used in steps 1) and 3) are at least one of the following: sodium hydroxide, sodium carbonate, ammonia, triethylamine, diethylamine, or triethanolamine.

4. The method for preparing core-shell silica microspheres according to claim 3, characterized in that... In step 1): The electrolytes are sodium chloride, potassium chloride, and lithium chloride; The solvent consists of deionized water and anhydrous ethanol; the volume ratio of deionized water to anhydrous ethanol is 1:6 to 8.

5. The method for preparing core-shell silica microspheres according to claim 4, characterized in that... In step 2): The cationic surfactant used as a template agent is at least one of the following: octadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, methyltrioctylammonium bromide, or polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer.

6. The method for preparing core-shell silica microspheres according to any one of claims 1 to 5, characterized in that... In step 2): The alcohol-water solution is obtained by mixing ethanol and water in a volume ratio of 1:(1±0.1). Each 0.1g of solid silica microspheres is mixed with 40-100ml of alcohol-water solution.

7. The method for preparing core-shell silica microspheres according to claim 6, characterized in that... In step 4): For every 0.1 g of solid silica microspheres, the corresponding silica core-shell microspheres of the composite template agent are prepared with 10–50 mL of (0.1 ± 0.02) M hydrochloric acid solution. The cleaning and drying process involves washing with water and ethanol alternately until the pH is neutral, followed by drying at 60±10℃ for 240±20 minutes.

8. The method for preparing core-shell silica microspheres according to claim 7, characterized in that... In step 4): After hydrothermal pore expansion, the temperature is increased to the required high-temperature calcination temperature at a heating rate of 1℃ / min.

9. Core-shell silica microspheres prepared by any one of the methods described in claims 1 to 8.

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