Preparation method of mesoporous monodisperse silica gel chromatographic microspheres

Abstract

The invention belongs to a preparation process of silica gel filler in ultra-high performance liquid chromatography separation, and particularly relates to a preparation method of mesoporous monodisperse silica gel microspheres (chromatographic microspheres). The method comprises the following steps: preparing microspheres by taking an alcohol-water solution as a solvent, tetraethoxysilane as a silicon source, lauryl amine and lauryl amine polyoxyethylene ether as template agents and ammonia water as a catalyst; ultrasonically dispersing the microspheres into a hydrochloric acid solution serving as an activating agent for activation, and then cleaning; ultrasonically dispersing the cleaned microspheres in deionized water, and sealing in a hydrothermal reaction kettle for high-temperature hydrothermal reaming; and calcining at high temperature to obtain the mesoporous monodisperse silica gel microspheres (chromatographic microspheres). By adopting the method disclosed by the invention, the silica gel filler which can be used for ultra-high performance liquid chromatography separation and is complete in sphere, high in mechanical strength, ideal in pore structure and controllable in particle size can be produced.

Description

Technical Field

[0001] The invention belongs to a preparation process of silica gel filler in ultra-high performance liquid chromatography separation, and particularly relates to a preparation method of mesoporous monodisperse silica gel chromatographic microspheres. Background Art

[0002] Chromatographic separation technology, also known as chromatography or chromatographic separation, is a highly efficient method for separating the components of complex mixtures. It relies on the differences in the distribution coefficients of different substances in a system consisting of a stationary phase and a mobile phase. Through the relative motion of the two phases, these substances migrate with the mobile phase and repeatedly distribute between the two phases, ultimately achieving separation. Based on this technical principle, high-performance liquid chromatography (HPLC) was developed. Its rapid, efficient, and highly sensitive analytical characteristics have made it widely used in fields such as food testing, environmental monitoring, and biomedicine.

[0003] The successful application of small particles has ushered in unprecedented separation capabilities in the field of separation science, marking the arrival of a new era of chromatography: ultra-high performance liquid chromatography (UPLC). HPLC typically uses columns with 5-micron particle size fillers. Compared to traditional HPLC, UPLC columns have finer filler particles, reaching 3.5 microns or even 1.5 microns. These finer particles significantly improve the efficiency of material separation and demonstrate greater separation potential. As a commercialized UPLC product, the Waters ACQUITY UPLC system uses innovative design concepts to significantly improve the resolution, sample handling capacity, and detection sensitivity of liquid chromatography. The commercialization of UPLC is not only a major leap forward in separation science, but also marks a new stage in the development of liquid chromatography technology.

[0004] The 30-year history of liquid chromatography is a history of particle technology development. Changes in particle size directly impact column efficiency, and thus separation results. As particle size decreases, chromatographic resolution improves. The theoretical basis for this behavior is the famous van der Meter equation. The resulting van der Meter curve is the fundamental basis for chromatographic scientists to predict chromatographic changes caused by particle size changes. This curve predicts the optimal column efficiency and the corresponding mobile phase flow rate. The curve shows that as particle size decreases, the corresponding height per theoretical plate (HETP) decreases, resulting in higher column efficiency. It should also be noted that the HETP minimum region for 1.7μm particles expands, indicating that maximum column efficiency can be achieved over a wider flow range than with larger particles, thus optimizing analysis speed without sacrificing high resolution.

[0005] Small particles offer such advantages in chromatographic separation efficiency and speed that utilizing small particle technology has become a coveted goal for chromatographic scientists. However, HPLC system design has been plagued by difficulties in fully utilizing the advantages of the smallest particles. The use of small particle technology not only requires operating instruments at pressures exceeding current limits (6000 psi / 400 bar), but also requires a smaller instrument system size to maintain gradient performance and detectors capable of high-speed detection of peaks with widths of only a few seconds.

[0006] The core component of ultra-high-performance liquid chromatography (UPLC) is the chromatographic column. As a crucial component of the column, the performance of the chromatographic packing directly determines the efficiency of UPLC. Currently, the HPLC packings on the market are primarily based on silica gel, with fully porous silica microspheres dominating the market. Fully porous silica microspheres suitable for use as chromatographic packings must possess the following advantages: 1) high purity and absence of metallic impurities; 2) intact spherical shape, small particle size, and monodispersity; 3) good mechanical strength and resistance to high pressure; 4) excellent pore structure and sufficient chemical modification sites; and 5) stable chemical properties.

[0007] During ultra-high-performance liquid chromatography (UPLC) operation, the silica microspheres in the chromatographic column undergo repeated adsorption and elution processes under high pressure. Due to the limited capacity of the silica microspheres, the column lifespan is also limited, making the column an ​​expensive consumable for UPLC. Currently, many foreign companies are focusing on developing small-particle porous silica microsphere chromatographic packing materials for ultra-high-performance liquid chromatography (UPLC). These products have been launched and dominate the major domestic and international markets. While chromatographic separation technology has advanced significantly in China in recent years, with domestically produced chromatographic columns successfully entering the market, the preparation processes for small-particle porous silica microspheres for UPLC remain limited. Patent application number 202310973675.3 discloses a method for preparing porous functional microspheres. However, the microspheres produced by this method exhibit poor sphericity, poor mechanical strength, and brittleness, resulting in an inability to provide stable separation results. Therefore, the ability to independently produce ideal chromatographic packing materials is crucial for the further development of chromatographic separation technology in China. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a method for preparing mesoporous monodisperse silica gel chromatographic microspheres with controllable pore size.

[0009] In order to solve the above technical problems, the present invention provides a method for preparing mesoporous monodisperse silica microspheres (chromatographic microspheres): using alcohol aqueous solution as solvent, tetraethyl orthosilicate as silicon source, dodecylamine and dodecylamine polyoxyethylene ether as templates, ammonia water as catalyst, and hydrochloric acid as activator.

[0010] As an improvement of the preparation method of the present invention, the following steps are included: 1) Add dodecylamine and dodecylamine polyoxyethylene ether as templates to an alcohol-water solution at 28-40°C and stir (magnetically stir) to dissolve the template (fully dissolve) to form a template solution; the mass ratio of dodecylamine to dodecylamine polyoxyethylene ether is (2±0.05):1; then, while continuing to stir (magnetically stir), add ethyl orthosilicate as a silicon source to the template solution, and then add concentrated aqueous ammonia as a catalyst to form a reaction solution; the volume ratio of ethyl orthosilicate to concentrated aqueous ammonia is 20±0.5:1; for every 1.0g of dodecylamine polyoxyethylene ether, use 8±0.5mL of ethyl orthosilicate; The reaction solution is allowed to stand for aging at 28-40°C under sealed conditions (stop aging when no new precipitate is generated), and the lower precipitate obtained by standing for aging is washed with alcohol and water (repeatedly washed with alcohol and water) to obtain microspheres; Note: The ammonia content of concentrated ammonia water is 25% to 28% (mass %); Since magnetic stirring is used, the rotor used for magnetic stirring needs to be removed from the reaction liquid before the reaction liquid is allowed to stand for aging. This is a common operating method in the industry. 2) Ultrasonic dispersion of the microspheres obtained in step 1) in a hydrochloric acid solution with a pH of 1 to 3 (preferably pH 1 to 1.8) as an activator for about 5 to 10 minutes, followed by activation at 28 to 40°C for 24 ± 2 hours, followed by washing with deionized water and filtering until the pH of the washing solution is neutral (the pH of the washing solution is neutral); thus, washed microspheres are obtained; 3) Ultrasonic dispersion of the cleaned microspheres obtained in step 2) in deionized water for about 5 to 10 minutes, and then sealing the microspheres in a hydrothermal reactor for high-temperature hydrothermal pore expansion. After cooling naturally, the microspheres are washed and filtered with anhydrous ethanol (twice) and vacuum dried to obtain dried microspheres. Note: The high-temperature hydrothermal pore expansion in this step can be performed in a muffle furnace; the microspheres are dispersed in deionized water for hydrothermal pore expansion to prevent uneven heating and pressure of the microspheres; 4) The dried microspheres obtained in step 3) are heated to 600±50° C. and calcined for 6±0.5 h; and then cooled naturally to obtain mesoporous monodisperse silica microspheres (chromatographic microspheres).

[0011] This shows that high-temperature calcination can not only remove the template, but also improve the mechanical strength of the microspheres; it can be carried out in a muffle furnace.

[0012] As a further improvement to the preparation method of the present invention, in step 1): The alcohol aqueous solution consists of methanol, isopropanol and water, with a volume ratio of methanol:isopropanol:water = (1±0.05): (1±0.05):1; For every 1.0g of dodecylamine polyoxyethylene ether, add (300±50)ml of alcohol aqueous solution.

[0013] As a further improvement of the preparation method of the present invention, In step 2), 100-150 ml of hydrochloric acid solution is added to every 1.0 g of microspheres prepared from polyoxyethylene laurylamine ether; In step 3), 40-60 ml of deionized water is added to each 1.0 g of washed microspheres prepared from dodecylamine polyoxyethylene ether.

[0014] As a further improvement to the preparation method of the present invention, in step 1): The stirring (magnetic stirring) speed is 400~800 rpm, After adding the template, the stirring time is 1 to 2 hours (so that the template is fully dissolved to form a template solution); After adding ethyl orthosilicate, stir for 1–4 min, then add concentrated aqueous ammonia and stir for 20–120 s (stop stirring before the reaction solution turns turbid). The static aging time is 1 to 6 days.

[0015] As a further improvement to the preparation method of the present invention, in step 3), the high-temperature hydrothermal pore expansion is performed by heating the temperature to 100-200° C. (preferably 100-120° C.) and maintaining the temperature for 24-48 hours.

[0016] Note: The higher the temperature and the longer the holding time, the larger the microsphere pore size. However, when the hydrothermal temperature is too high or the holding time is too long, excessive pore expansion may occur, i.e., the microsphere pores become too large, the specific surface area decreases, and the mechanical strength of the microspheres also decreases. Therefore, it is necessary to perform high-temperature hydrothermal pore expansion within the temperature and holding time ranges specified in this invention.

[0017] As a further improvement to the preparation method of the present invention, the heating rate of step 3) high-temperature hydrothermal pore expansion is 5±0.5°C / min; The heating rate of the high-temperature calcination in step 4) is 2±0.5°C / min.

[0018] As a further improvement to the preparation method of the present invention, the vacuum drying in step 3) is: vacuum drying at 60±10° C. for 6±1 h.

[0019] The present method for preparing mesoporous monodisperse silica microspheres (chromatographic microspheres) does not involve the introduction of metal elements throughout the entire preparation process, significantly improving the purity of the silica microspheres. The resulting microspheres exhibit excellent monodispersity, high mechanical strength, and a narrow pore size distribution. The reaction temperature can be controlled to achieve minute variations in microsphere size between 1 and 2 μm. Compared to conventional 5 μm microsphere fillers, the mesoporous microspheres prepared in this invention have a smaller particle size. According to the Van Deemeter equation, smaller particle size results in a smaller theoretical step height and higher column efficiency, thus shortening analysis time, improving separation efficiency, and reducing solvent usage, better meeting the requirements for efficient and rapid separations. This preparation method is simple to operate and easily scalable, and the production system is stable.

[0020] In the entire preparation process of the present invention, the reaction temperature affects the particle size of the microspheres. The temperature control is mainly concentrated in step 1) the magnetic stirring and aging process, and step 2) the hydrochloric acid activation process. The effect of temperature on the particle size and morphology of the microspheres is mainly investigated.

[0021] In summary, the method of the present invention can produce silica gel fillers with complete spherical shape, high mechanical strength, ideal pore structure and controllable particle size that can be used for ultra-high performance liquid chromatography separation. Promote the development of chromatographic separation technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The specific embodiments of the present invention are further described in detail below with reference to the accompanying drawings.

[0023] Figure 1 This is a scanning electron microscope image of a monodisperse silica gel microsphere provided in Example 1; Figure 2 This is a scanning electron microscope image of a monodisperse silica gel microsphere provided in Example 2; Figure 3 This is a scanning electron micrograph of monodisperse silica gel microspheres provided in Example 3-1; Figure 4 This is a scanning electron microscope image of a monodisperse silica gel microsphere provided in Example 4; Figure 5 This is a scanning electron micrograph of a monodisperse silica gel microsphere provided in Example 5; Figure 6 This is a scanning electron microscope image of monodisperse silica gel microspheres provided in Example 6. DETAILED DESCRIPTION

[0024] The present invention will be further described in detail below through specific implementation. It should be noted that the following embodiments are limited to the present invention, but are not intended to limit the scope of implementation of the present invention.

[0025] Example 1: A method for preparing mesoporous monodisperse silica gel chromatographic microspheres is carried out at room temperature of 27°C to 35°C in summer. The following steps are performed in sequence: 1) At room temperature in summer, 100 mL of methanol, 100 mL of isopropanol, and 100 mL of deionized water were added to a 500 mL beaker as a solvent. Then, 2.0 g of dodecylamine and 1.0 g of dodecylamine polyoxyethylene ether, two templates, were added. The mixture was magnetically stirred at 500 rpm for 1 h to fully dissolve the templates and form a template solution. While continuing to stir, 8 mL of ethyl orthosilicate was added. After 1 min, 0.4 mL of concentrated ammonia water (mass concentration of ammonia was 25% to 28%) was quickly added. The mixture was stopped immediately after 20 s. The rotor was quickly removed and the beaker was sealed with plastic wrap. The reaction solution was allowed to stand at room temperature in summer for 24 h (no new precipitate was generated at this time). The lower precipitate obtained after standing and aging was repeatedly washed with alcohol and water to obtain microspheres. Note: The alcohol washing method above uses anhydrous ethanol. The purpose of alcohol washing is to wash away free chain polymers and prevent adhesion and agglomeration between microspheres. The number of alcohol washing times is 2 to 3 times. The purpose of the above water washing is to wash away the residual ammonia; the water washing is stopped when the pH is neutral.

[0026] 2) At room temperature in summer, the microspheres obtained in step 1) were added to 100 ml of hydrochloric acid solution (pH = 1) and ultrasonically dispersed for 5 minutes, so that the microspheres can be evenly dispersed in the hydrochloric acid solution; Then, the microspheres were left to stand and activated for 24 h at room temperature in summer, and then washed and filtered with deionized water several times until the washing solution became neutral, thus obtaining the washed microspheres. 3) At room temperature in summer, the washed microspheres obtained in step 2) were added to 50 mL of deionized water and ultrasonically dispersed for 5 minutes, so that the microspheres can be evenly dispersed in the deionized water; then sealed in a hydrothermal reactor of corresponding specifications (slightly larger than 50 mL), the reactor was placed in a muffle furnace, and high-temperature hydrothermal pore expansion was performed, the temperature was increased to 100 ° C at a rate of 5 ° C / min, and the temperature was kept for 24 hours. After natural cooling, the microspheres were washed and filtered twice with anhydrous ethanol (so that the microspheres no longer agglomerated), and vacuum dried at 60 ° C for 6 hours; 4) The dried microspheres obtained in step 3) were placed in a muffle furnace and calcined at high temperature to remove the template and improve the mechanical strength of the microspheres. The muffle furnace was heated at a rate of 2 °C / min to 600 °C and maintained for 6 h. After cooling naturally, mesoporous monodisperse silica gel chromatographic microspheres were obtained.

[0027] Note: If the temperature is not clearly defined in this embodiment, all experiments were carried out at room temperature as defined in this embodiment.

[0028] The morphology of the monodisperse silica microspheres obtained in Example 1 is as follows: Figure 1As shown by Figure 1 As can be seen from the scanning electron microscope photos in the figure, the particle size of the monodisperse silica microspheres is 1.5 μm, with high sphericity and no agglomeration; the particle size distribution is narrow, D90 / D10=1.84; and the average pore diameter is 9.15 nm.

[0029] Example 2: With respect to Example 1, the "summer room temperature of 27°C to 35°C" is changed to "normal room temperature of 18°C ​​to 25°C"; the rest is the same as Example 1.

[0030] The morphology of the prepared silica microspheres varies. The morphology of the monodisperse silica microspheres provided in Example 2 is as follows: Figure 2 As shown in the figure, the particle size is 2.0 μm, but the sphericity is poor and there is agglomeration between the microspheres.

[0031] Example 3-1: Compared with Example 1, the "summer room temperature of 27°C to 35°C" is changed to "constant temperature of 28°C"; Also, change the pH of the hydrochloric acid solution in step 2) from "pH = 1" to "pH = 1.5"; The rest is the same as Example 1.

[0032] Note: To ensure constant temperature, the beaker in step 1) was placed on a magnetic stirring hot plate set at a constant temperature of 28°C. The aging in step 1) and the activation in step 2) were both performed in a 28°C thermostat. The ultrasonic dispersion in step 3) was also performed at a constant temperature of 28°C. That is, this Example 3-1 is based on the experience of Example 1 and Example 2. In order to avoid the influence of ambient temperature changes on the experiment and keep the experimental temperature stable, a constant temperature equipment magnetic stirring heating plate and a constant temperature box are introduced to accurately control the experimental temperature.

[0033] The morphology of the monodisperse silica microspheres obtained in Example 3-1 is as follows: Figure 3 As shown by Figure 3 The SEM images show that the monodisperse silica microspheres have a particle size of 1.6 μm, high sphericity, and no agglomeration. D90 / D10 = 1.69.

[0034] Example 3-2: Compared with Example 3-1, the hydrothermal conditions for hydrothermal pore expansion in step 3) were changed from "100° C., 24 h" to "120° C., 24 h", and the rest were the same as Example 3-1.

[0035] Example 3-3: Compared with Example 3-1, the hydrothermal conditions for hydrothermal pore expansion in step 3) were changed from "100° C., 24 h" to "100° C., 48 h", and the rest were the same as Example 3-1.

[0036] The mesoporous monodisperse silica gel chromatographic microspheres obtained in Examples 3-1 to 3-3 above showed no agglomeration phenomenon, as shown in Table 1 below.

[0037] Table 1

[0038] According to Table 1, time and temperature have an impact on the pore structure of silica gel microspheres. Increasing temperature and prolonging time will increase the pore diameter, but at the same time the specific surface area and pore volume will decrease.

[0039] Example 3-4: Compared with Example 3-1, the hydrothermal temperature for hydrothermal pore expansion in step 3) is changed from "100°C" to "150°C" or "200°C", and the hydrothermal time remains unchanged at 24h. The rest is the same as Example 3-1.

[0040] The results showed that at 150°C, some microspheres showed hollowing and damage, and at 200°C, the hollowing and damage phenomenon increased significantly, indicating that high temperature expanded the pore structure of the microspheres, but excessive temperature and pressure would cause excessive etching, which greatly reduced the mechanical strength of the microspheres.

[0041] Example 4: Compared with Example 3-1, the constant temperature is changed from "28°C" to "35°C", and the rest is the same as Example 3-1.

[0042] The morphology of the monodisperse silica microspheres obtained in Example 4 is as follows: Figure 4 As shown in Table 2, the particle size is 1.1 μm, with high sphericity and no agglomeration.

[0043] Table 2

[0044] Example 5: Compared with Example 3-1, the constant temperature is changed from "28°C" to "40°C", and the rest is the same as Example 3-1.

[0045] The morphology of the monodisperse silica microspheres obtained in Example 5 is as follows: Figure 5 As shown in Table 3, the particle size is 0.9 μm, with high sphericity and no agglomeration.

[0046] Table 3

[0047] Verification experiment 1: To verify the scale-up of the reaction system by 10 times, the experimental temperature was 30 °C. Since the amount of reaction material was scaled up by 10 times, a 5L spherical magnetic stirring heating jacket was used instead of the flat magnetic stirring heating plate to provide a uniform reaction temperature.

[0048] Specifically, perform the following steps in sequence: 1) Add 1.0 L methanol, 1.0 L isopropanol, and 1.0 L deionized water to a 5 L round-bottom flask, then add 20.0 g dodecylamine and 10.0 g dodecylamine polyoxyethylene ether, two templates. Place the round-bottom flask on a magnetic stirring heating mantle, set the heating mantle to a constant temperature of 30°C, place it in a magnetic rotor of corresponding size, and stir magnetically at 800 rpm for 2 h to fully dissolve the template to form a template solution. While continuing to stir, add 80 mL of ethyl orthosilicate. After 4 minutes, quickly add 4.0 mL of concentrated ammonia water. Stop immediately after 2 minutes. Transfer the reaction solution to a 5 L beaker and seal it with plastic wrap. Then place it in a constant temperature box at 30°C for aging for 6 days (no new precipitate is produced at this time). The lower precipitate is repeatedly washed with alcohol and water to obtain microspheres. 2) The microspheres prepared in step 1) were uniformly dispersed in a hydrochloric acid solution with a pH of 1.8 by ultrasonication for 5 minutes, sealed with plastic wrap, and placed in a 30°C thermostat for activation for 24 hours. The microspheres were then washed with deionized water and filtered several times until the washing solution was neutral, thereby obtaining washed microspheres. 3) The cleaned microspheres obtained in step 2) were ultrasonically dispersed again for 10 minutes in 400 mL of deionized water and sealed in two hydrothermal reactors of corresponding specifications (slightly larger than 200 mL). The reactors were placed in a forced air drying oven for high-temperature hydrothermal pore expansion at 100°C for 24 hours. After natural cooling, the microspheres were washed with anhydrous ethanol and centrifuged twice, and then vacuum dried at 60°C for 6 hours. 4) The dried microspheres obtained in step 3) were placed in a muffle furnace and calcined at high temperature to remove the template and improve the mechanical strength of the microspheres. The muffle furnace was heated at a rate of 2 °C / min to 600 °C and maintained for 6 h. After cooling naturally, mesoporous monodisperse silica gel chromatographic microspheres were obtained.

[0049] The morphology of the monodisperse silica microspheres in the verification experiment 1 is as follows Figure 6 As shown by Figure 6 The SEM images show that the monodisperse silica microspheres have a particle size of 1.7 μm, high sphericity, and no agglomeration. The particle size distribution is narrow, with a D90 / D10 ratio of 1.83, and the average pore size is 11.2 nm.

[0050] Comparative Example 1: With respect to Example 3-1, “100 mL of methanol, 100 mL of isopropanol, and 100 mL of deionized water” was changed to “150 mL of ethanol and 150 mL of deionized water”, and the rest was the same as Example 3-1.

[0051] The prepared microspheres have serious agglomeration phenomenon, small pore volume and pore size, poor monodispersity and poor microsphere morphology.

[0052] Comparative Example 2: Compared with Example 3-1, “2.0 g of dodecylamine and 1.0 g of dodecylamine polyoxyethylene ether” was changed to “1.5 g of dodecylamine and 1.5 g of dodecylamine polyoxyethylene ether”, and the rest was the same as Example 3-1.

[0053] The prepared microspheres have serious agglomeration phenomenon, small pore volume and pore size, poor monodispersity and poor microsphere morphology.

[0054] The comparison between Comparative Example 1, Comparative Example 2 and Example 3-1 is shown in Table 4 below.

[0055] Table 4

[0056] Comparative Example 3: Compared to Example 3-1, in step 1), the reaction solution was stirred at 360 rpm for 2 hours, instead of aging for 24 hours. The remaining reaction mixture was identical to Example 3-1. The resulting product was lumpy and could not be formed into a complete sphere.

[0057] Comparative Example 4: Relative to Example 3-1, step 3) was modified from "After cleaning, the microspheres were uniformly dispersed in 50 mL of deionized water; then, sealed in a hydrothermal reactor, the microspheres were subjected to high-temperature hydrothermal pore expansion, heating to 100°C at a rate of 5°C / min and maintaining the temperature for 24 hours" to "The microspheres were placed in a hydrothermal reactor, 0.01 M ammonia (50 mL) was added, and the reaction was hydrothermally reacted at 120°C for 48 hours." The remaining steps were identical to those in Example 3-1. The sample prepared in Comparative Example 4 exhibited significant crystallization. Under high temperature, the silica microspheres were etched and dissolved by the alkaline solution, reorganizing into crystalline blocks. The desired mesoporous monodisperse silica chromatographic microspheres could not be obtained.

[0058] Finally, it should be noted that the above examples are merely specific embodiments of the present invention. Obviously, the present invention is not limited to the above examples and is subject to numerous variations. All variations that can be directly derived or conceived by a person of ordinary skill in the art from the disclosure of the present invention are considered to be within the scope of protection of the present invention.

Claims

1. A method for preparing mesoporous monodisperse silica microspheres, characterized by: The method uses alcohol aqueous solution as solvent, ethyl orthosilicate as silicon source, dodecylamine and dodecylamine polyoxyethylene ether as templates, ammonia water as catalyst, and hydrochloric acid as activator.

2. The preparation method according to claim 1, wherein The following steps are involved: 1) Add dodecylamine and dodecylamine polyoxyethylene ether as templates to a solvent at 28-40°C and stir to dissolve the templates to form a template solution; the mass ratio of dodecylamine to dodecylamine polyoxyethylene ether is (2±0.05):1; then, while continuing to stir, add ethyl orthosilicate as a silicon source and then add concentrated aqueous ammonia as a catalyst to the template solution to form a reaction solution; the volume ratio of ethyl orthosilicate to concentrated aqueous ammonia is 20±0.5:1; for every 1.0g of dodecylamine polyoxyethylene ether, use 8±0.5mL of ethyl orthosilicate; The reaction solution is placed in a sealed condition at 28-40°C for aging, and the lower precipitate obtained by the aging is washed with alcohol and water to obtain microspheres; 2) Ultrasonic dispersion of the microspheres obtained in step 1) in a hydrochloric acid solution with a pH of 1 to 3, activation at 28 to 40° C. for 24 ± 2 h, and then washing with deionized water and filtering to neutrality to obtain washed microspheres; 3) Ultrasonic dispersion of the cleaned microspheres obtained in step 2) in deionized water, sealing the microspheres in a hydrothermal reactor, and then performing high-temperature hydrothermal pore expansion. After cooling naturally, the microspheres are washed and filtered with anhydrous ethanol and vacuum dried to obtain dried microspheres. 4) The dried microspheres obtained in step 3) are heated to 600±50° C. and calcined for 6±0.5 h; and then cooled naturally to obtain mesoporous monodisperse silica microspheres.

3. The preparation method according to claim 2, wherein In the step 1): The alcohol aqueous solution consists of methanol, isopropanol and water, with a volume ratio of methanol:isopropanol:water = (1±0.05): (1±0.05):1; For every 1.0g of dodecylamine polyoxyethylene ether, add (300±50)ml of alcohol aqueous solution.

4. The preparation method according to claim 3, characterized in that In the step 1): In step 2), 100-150 ml of hydrochloric acid solution is added to every 1.0 g of microspheres prepared from polyoxyethylene laurylamine ether; In step 3), 40-60 ml of deionized water is added to each 1.0 g of washed microspheres prepared from dodecylamine polyoxyethylene ether.

5. The preparation method according to claim 4, characterized in that In the step 1): The stirring speed is 400~800 rpm, The stirring time after adding the template is 1~2 h; After adding ethyl orthosilicate, stir for 1–4 min, then add concentrated ammonia solution and stir for 20–120 s. The static aging time is 1 to 6 days.

6. The preparation method according to any one of claims 1 to 5, characterized in that In step 3), the high-temperature hydrothermal pore expansion is performed by heating the pores to 100-200° C. and maintaining the temperature for 24-48 hours.

7. The preparation method according to claim 6, characterized in that: The heating rate of step 3) high-temperature hydrothermal pore expansion is 5±0.5°C / min; The heating rate of the high-temperature calcination in step 4) is 2±0.5°C / min.

8. The preparation method according to claim 7, characterized in that The vacuum drying in step 3) is as follows: vacuum drying at 60±10° C. for 6±1 h.

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