Preparation method of acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres

Abstract

This invention provides a method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres. It utilizes non-porous titanium dioxide microspheres as the core and a porous polymer shell to coat the non-porous titanium dioxide microspheres, thereby improving the material's acid and alkali resistance and expanding the application range of core-shell fillers. The porous polymer shell exhibits high chemical stability and can be applied over a wide pH range. Furthermore, the large pore size of the porous shell makes it particularly suitable for the rapid separation and analysis of biomolecules.

Description

Technical Field

[0001] This invention relates to the field of chromatographic media preparation technology, and in particular to a method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres. Background Technology

[0002] Core-shell titanium dioxide microspheres, as a new generation of chromatographic packing materials, have attracted widespread attention from chromatographic researchers due to their superior performance in terms of high efficiency, speed, high resolution, and low back pressure. Core-shell packing materials possess a unique non-porous core and mesoporous shell structure. This special structure ensures high mechanical strength while significantly shortening the solute diffusion path, thus greatly reducing the separation time required, making them particularly suitable for the rapid separation of biomolecules. Horvath was the first to apply core-shell microspheres to chromatographic separation processes. [4] Later, Kirkland's team refined and improved this technology. In particular, Kirkland commercialized sub-3 μm core-shell packing material in 2006, representing a breakthrough in the preparation and application of core-shell microspheres, which sparked significant attention and research enthusiasm among scientists. Our research group has achieved good results in the rapid chromatographic separation of small molecules and proteins using core-shell chromatographic packing materials prepared by the dual-template method and polymerization-induced redeposition method, respectively. However, the pH range of silica-based stationary phases is limited to 2.0-8.0, which greatly restricts their application. Furthermore, due to the weakly acidic surface of silica, residual silanol groups readily undergo irreversible adsorption with polar biomolecules, causing peak broadening, tailing, and loss of the analyzed sample. Therefore, the application of titanium dioxide core-shell matrices in the rapid separation and analysis of monoclonal antibodies is significantly limited.

[0003] Polymer-based chromatographic packing materials have advantages such as high chemical stability, easy derivatization, strong loading capacity, low non-specific adsorption, and high chromatographic capacity. They also have good biocompatibility and are especially suitable for the separation and analysis of biological samples. However, polymer materials have low pressure resistance and poor mechanical strength.

[0004] To address the above problems, this invention prepares a titanium dioxide@porous polymer core-shell chromatographic packing material by uniformly coating a porous polymer onto the surface of solid titanium dioxide microspheres. The material possesses high mechanical strength and high pressure resistance, while also exhibiting the advantages of polymer packing materials, such as wide applicability, no non-specific adsorption, and rapid separation, making it suitable for rapid separation and analysis in liquid chromatography. Summary of the Invention

[0005] To address the aforementioned issues, this invention provides a method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres, which improves the acid and alkali resistance of the material and facilitates the expansion of the application range of core-shell packings. Its porous polymer shell exhibits high chemical stability and can be applied over a wide pH range, and the large pore size of the porous shell makes it particularly suitable for the rapid separation and analysis of biomolecules.

[0006] The objective of this invention is achieved by providing a method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres, comprising the following steps:

[0007] (1) Preparation of titanium dioxide@polystyrene core-shell microspheres

[0008] Micron-sized monodisperse titanium dioxide@polystyrene core-shell microspheres were prepared by dispersion polymerization using nonporous titanium dioxide microspheres as the core, styrene and 2-vinylbenzene as monomers, sodium p-styrene sulfonate (NaSS) and 3-(methacryloyloxy)propyltrimethoxysilane (KH-570) as auxiliaries, and potassium persulfate (KPS) as the initiator. The volume ratio of 2-vinylbenzene to styrene was 1:9 to 2:8.

[0009] (2) Preparation of titanium dioxide@porous polymer core-shell microspheres

[0010] Titanium dioxide@polystyrene core-shell microspheres are used as the parent spheres. Using a seed swelling method, an emulsion containing functional monomers, crosslinking agents, and pore-forming agents is uniformly absorbed into the polystyrene shell. A polymerization reaction is initiated in the presence of surfactants. After removing the pore-forming agents from the product, titanium dioxide@porous polymer core-shell microspheres are obtained.

[0011] In step (2), glycidyl methacrylate (GMA) is used as the monomer, ethylene glycol dimethacrylate (EDMA) is used as the crosslinking agent, and butyl acetopropionate is used as the pore-forming agent.

[0012] In step (2), the surfactant includes polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS). The mass percentage concentration of polyvinyl alcohol is 0.1-0.5% and the mass percentage concentration of sodium dodecyl sulfate is 1-5%. PVA provides steric hindrance protection and SDS provides electrostatic protection to avoid adhesion and aggregation between microspheres.

[0013] Step (1) involves dispersing non-porous titanium dioxide microspheres (TiO2) in an ethanol solution in a three-necked flask, purging with nitrogen using ultrasound, and then adding KPS, NaSS, and KH-570. The mixture is stirred and heated at 300-500 r / min until the solution temperature reaches 70°C. Then, 0.8-0.9 ml of styrene and 0.1-0.2 ml of divinylbenzene (DVB) are dispersed evenly in anhydrous ethanol and slowly added dropwise to the three-necked flask. The mixture is reacted at 70°C for 12 hours. After the reaction is complete, the mixture is washed with anhydrous ethanol until the solution is clear and no small particles are observed under a microscope. Finally, it is placed in a 60°C constant temperature oven and dried for 12 hours.

[0014] In step (1), the monodisperse nonporous titanium dioxide microspheres are obtained through the following steps: In the Stober system, monodisperse nonporous titanium dioxide microspheres with controllable particle size are prepared by sol-gel process using alkyl alcohol as solvent, titanate as titanium source, and electrolyte (NaCl, KCl, LiCl) as particle size regulator. The electrolyte is NaCl, KCl or LiCl.

[0015] Step (2) involves weighing 0.1 g of titanium dioxide@polystyrene core-shell microspheres into a 100 ml three-necked flask, adding 10-40 ml of SDS solution, ultrasonically dispersing for 20-60 min, then adding 5-20 ml of PVA and ultrasonically dispersing for 10-20 min, then placing it in a 30°C water bath and stirring at 150-350 r / min for 1 hour; then ultrasonically mixing 0.01-0.04 g of BPO, 0.1-0.4 ml of GMA, 0.1-0.4 ml of EDMA, 0.13-1.2 ml of butyl levulinate, 10-40 ml of SDS, and 5-20 ml of PVA until homogeneous, and then adding the mixture dropwise to the above solution, stirring in a 30°C water bath for 6 hours; then raising the temperature to 70°C under nitrogen protection and stirring for 12 hours; after the reaction is complete, rinsing the obtained product with deionized water at 2000 mL / min. Centrifuge three times at rpm, then wash with plenty of 60°C hot water until the filtrate is free of foam, and finally wash once with anhydrous ethanol. Then place it in a vacuum drying oven and dry at 60°C for 12 hours.

[0016] Compared with existing technologies, the titanium dioxide@porous polymer core-shell microspheres prepared in this invention utilize non-porous titanium dioxide microspheres as the core and a porous polymer shell to coat the non-porous silica microspheres, thereby improving the acid and alkali resistance of the material and expanding the application range of the core-shell filler. Its porous polymer shell has high chemical stability and can be used in a wide pH range, and the pore size of the porous shell is relatively large, making it particularly suitable for the rapid separation and analysis of biomacromolecules.

[0017] This invention uses emulsion polymerization to prepare titanium dioxide@porous polymer core-shell microspheres with a large pore size structure. The preparation process is simple, the raw materials are inexpensive, and it is easy to control and scale up.

[0018] By using inert organic small molecules as pore-forming agents, pore structures with large sizes can be prepared, which are particularly suitable for rapid analysis of biomacromolecules.

[0019] By adjusting the mass ratio of organic monomer to silicon core from 2:1 to 8:1, the shell thickness can be controlled within the range of 100~200 nm. By adjusting the mass ratio of monomer to pore-forming agent from 5:2 to 5:3, the pore size can be controlled within the range of 30~60 nm.

[0020] The acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres prepared in this invention have a large pore size and are composed of a solid titanium dioxide core and a porous polymer shell. The solid inner core not only increases the mechanical stability of the packing material, but also increases the permeability and thermal conductivity of the chromatographic bed. Most importantly, it reduces the dispersion path of the solute in the packing material. These factors can reduce the B and C terms in the Van Diem equation and increase the theoretical plate number. The porous organic shell increases the specific surface area of ​​the material, improves column efficiency and resolution, and expands the application range of core-shell packing materials, especially suitable for the separation and analysis of biomacromolecules. Attached Figure Description

[0021] Figure 1 This is a roadmap for the preparation of titanium dioxide@porous polymer core-shell microspheres according to the present invention;

[0022] Figure 2 These are scanning electron microscope images of the non-porous titanium dioxide microspheres prepared according to the present invention;

[0023] Figure 3 These are scanning electron microscope images of the titanium dioxide@polystyrene core-shell microspheres prepared in this invention;

[0024] Figure 4 These are transmission electron microscope images of the titanium dioxide@polystyrene core-shell microspheres prepared in this invention;

[0025] Figure 5 These are scanning electron microscope images of the titanium dioxide@porous polymer core-shell microspheres prepared in this invention;

[0026] Figure 6 These are transmission electron microscope images of titanium dioxide@porous polymer core-shell microspheres prepared in this invention;

[0027] Figure 7 This is a pore size distribution diagram of the titanium dioxide@porous polymer core-shell microspheres prepared in this invention;

[0028] Figure 8 This is a transmission electron microscope image of the titanium dioxide@porous polymer core-shell microspheres prepared in this invention after an acid resistance test;

[0029] Figure 9 This is a transmission electron microscope image of the titanium dioxide@porous polymer core-shell microspheres prepared in this invention after an alkali resistance test. Detailed Implementation

[0030] The present invention will now be described in detail with reference to specific embodiments. It should be noted that these embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the above description of the present invention.

[0031] A method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres includes the following steps:

[0032] (1) Preparation of titanium dioxide@polystyrene core-shell microspheres

[0033] Micron-sized monodisperse titanium dioxide@polystyrene core-shell microspheres were prepared by dispersion polymerization using nonporous titanium dioxide microspheres as the core, styrene and 2-vinylbenzene as monomers, sodium p-styrene sulfonate (NaSS) and 3-(methacryloyloxy)propyltrimethoxysilane (KH-570) as auxiliaries and potassium persulfate (KPS) as initiator. The volume ratio of 2-vinylbenzene to styrene was 1:9 to 2:8.

[0034] (2) Preparation of titanium dioxide@porous polymer core-shell microspheres

[0035] Titanium dioxide@polystyrene core-shell microspheres are used as the parent spheres. Using a seed swelling method, an emulsion containing functional monomers, crosslinking agents, and pore-forming agents is uniformly absorbed into the polystyrene shell. A polymerization reaction is initiated in the presence of surfactants. After removing the pore-forming agents from the product, titanium dioxide@porous polymer core-shell microspheres are obtained.

[0036] In step (1), the monodisperse nonporous titanium dioxide microspheres are achieved through the following steps: within the Stober system, using alkyl alcohols (CH3-(CH2)) X Monodisperse, nonporous titanium dioxide microspheres with controllable particle size were prepared by a sol-gel process using titanates (ethyl titanate, propyl titanate, butyl titanate) as solvents, titanates (ethyl titanate, propyl titanate, butyl titanate) as titanium sources, and electrolytes (NaCl, KCl, LiCl) as particle size modifiers.

[0037] The roadmap for preparing titanium dioxide@porous polymer core-shell microspheres according to this invention is as follows: Figure 1 As shown.

[0038] The preparation method of titanium dioxide@porous polymer core-shell microspheres includes the following steps:

[0039] (1) Preparation of non-porous titanium dioxide microspheres

[0040] First, add 200-300 mL of anhydrous ethanol and an appropriate amount of electrolyte solution to a clean three-necked flask, and disperse evenly by ultrasonication. Then, add an appropriate amount of tetraethyl orthotitanate dropwise to the above mixed solution. After the addition is complete, keep the reaction conditions unchanged and continue the reaction for 1-10 min. Then, add a certain amount of vinyltriethoxytitane (VTEO) diluted with ethanol, and continue the reaction for 1-10 min. After the reaction is complete, wash with anhydrous ethanol by centrifugation at 3000 rpm. Place the washed product in a vacuum drying oven at 50°C for 12 h.

[0041] (2) Preparation of titanium dioxide@polystyrene core-shell microspheres

[0042] In a three-necked flask, TiO2 from (1) was dispersed in an ethanol solution, sonicated and purged with nitrogen, and then KPS, NaSS, and 3-(methacryloyloxy)propyltrimethoxysilane (KH-570) were added. The mixture was stirred and heated at 300-500 r / min. After the temperature of the three-necked flask and the solution reached 70℃, 0.8-0.9 ml of styrene and 0.1-0.2 ml of divinylbenzene (DVB) were dispersed evenly with a small amount of anhydrous ethanol and slowly added dropwise to the three-necked flask. The mixture was reacted at 70℃ for 12 hours. After the reaction was completed, the mixture was washed with anhydrous ethanol until the solution was clear and no small particles were observed under a microscope. Then, it was placed in a 60℃ constant temperature oven to dry for 12 hours.

[0043] (3) Preparation method of silica@porous polymer core-shell microspheres

[0044] Weigh 0.1 g of titanium dioxide@polystyrene core-shell microspheres into a 100 ml three-necked flask, add 10-40 ml of SDS solution, and sonicate for 20-60 min. Then add 5-20 ml of PVA and sonicate for 10-20 min. Place the flask in a 30°C water bath and stir at 150-350 r / min for 1 hour. Then, sonicate 0.01-0.04 g of BPO, 0.1-0.4 ml of GMA, 0.1-0.4 ml of EDMA, 0.13-1.2 ml of butyl levulinate, 10-40 ml of SDS, and 5-20 ml of PVA until homogeneous, and add this mixture dropwise to the above solution. Stir in a 30°C water bath for 6 hours. Then, under nitrogen protection, raise the temperature to 70°C and stir for 12 hours. After the reaction was completed, the product was centrifuged three times at 2000 rpm with deionized water, then washed with a large amount of 60°C hot water until the filtrate was free of foam, and finally washed once with anhydrous ethanol. After that, it was placed in a vacuum drying oven and dried at 60°C for 12 hours.

[0045] 1. Preparation of titanium dioxide@porous polymer core-shell microspheres

[0046] Example 1

[0047] (1) Preparation of non-porous titanium dioxide microspheres

[0048] A typical method for preparing micron-sized solid titanium dioxide microspheres is as follows: 200 mL of anhydrous ethanol and 1 mL of KCl solution are added to a 500 mL three-necked flask and ultrasonically dispersed until homogeneous. Then, 1 mL of tetraethyl orthotitanate is added under rapid stirring at 500 r / min. After the addition is complete, the reaction conditions are kept constant, and the reaction is continued for 10 min. Then, 10 mL of vinyltriethoxytitane (10 wt%) diluted in ethanol is added, and the reaction is continued for another 10 min. After the reaction is complete, the product is washed with anhydrous ethanol by centrifugation at 3000 rpm. The washed product is then dried in a vacuum drying oven at 50°C for 12 h. Microspheres with a particle size of 2.1 μm are selected as the core, and the morphology of the microspheres is shown in [Figure showing morphology]. Figure 2 .

[0049] (2) Preparation of titanium dioxide@polystyrene core-shell microspheres

[0050] Take 0.5 g of TiO2 from (1) and disperse it in 40 ml of 65% ethanol solution. Sonicate for 10 min, purge with nitrogen for 1 hour, then add 0.08 g KPS, 0.04 g NaSS and 0.2 ml KH-570. Stir and heat at 300 r / min. After the temperature of the three-necked flask and the solution reaches 70℃, take a certain amount of styrene and divinylbenzene (DVB) mixed solution (Table 1), disperse it evenly with a small amount of anhydrous ethanol, and slowly add it dropwise to the three-necked flask. React at 70℃ for 12 hours. After the reaction is complete, wash with anhydrous ethanol until the solution is clear and no small particles are observed under a microscope. Then place it in a 60℃ constant temperature oven to dry for 12 hours.

[0051] Table 1. Proportions of titanium dioxide@polystyrene core-shell microspheres with different degrees of crosslinking

[0052]

[0053] (3) Preparation of silica@porous polymer core-shell microspheres

[0054] Weigh 0.1 g of titanium dioxide@polystyrene core-shell microspheres (SiO2@PS) with different formulations in (2), transfer to a 100 ml three-necked flask, add 40 mL of 0.25% SDS and sonicate for 20 min, then add 20 mL of 5% PVA and sonicate for 10 min. Stir at 30 ℃ and 250 r / min for 1 hour to obtain a silica gel suspension. Next, disperse 0.01 g BPO, 0.1 mL GMA, 0.1 mL EDMA, and 0.13 mL butyl levulinate in a mixed solution of 20 mL of 0.25% SDS and 10 mL of 5% PVA, and sonicate until uniformly dispersed. Then, at a low speed of 150 r / min, dropwise add the dispersed monomer mixture to the silica gel suspension and react at 30 ℃ for 6 hours. Then, nitrogen gas was purged for 30 minutes, the temperature was raised to 70 °C, and the reaction was continued for 12 hours. The resulting product was centrifuged three times at 2000 rpm with deionized water, then washed with a large amount of 60 °C hot water until the filtrate was free of foam. Finally, it was washed once with anhydrous ethanol and placed in a vacuum drying oven to dry overnight at 60 °C. The results are shown in Table 2 below.

[0055] Table 2. Effect of different degrees of crosslinking on titanium dioxide@porous polymer core-shell microspheres

[0056]

[0057] Based on the results in Table 2, titanium dioxide@polystyrene core-shell microspheres with a crosslinking degree in the range of 0.1-0.2 were selected as seeds for the next step of swelling polymerization.

[0058] Example 2

[0059] (2) Preparation of titanium dioxide@polystyrene core-shell microspheres

[0060] Take 0.5 g of TiO2 from Example 1 (1) and disperse it in 40 ml of 65% ethanol solution. Sonicate for 10 min, purge with nitrogen for 1 hour, then add 0.08 g KPS, 0.04 g NaSS, and 0.2 ml KH-570. Stir and heat at 300 r / min. After the temperature of the three-necked flask and solution reaches 70℃, take 0.9 ml of styrene and 0.1 mL of DVB and disperse them evenly with a small amount of anhydrous ethanol. Slowly add the mixture to the three-necked flask with a dropper and react at 70℃ for 12 hours. After the reaction is complete, wash with anhydrous ethanol until the solution is clear and no small particles are observed under a microscope. Then dry it in a 60℃ constant temperature oven for 12 hours. Scanning electron microscope (SEM) and transmission electron microscope (TEM) images of titanium dioxide@polystyrene core-shell microspheres are shown below. Figure 3 and Figure 4 As shown.

[0061] Based on transmission electron microscopy images, the shell thickness of the titanium dioxide@polystyrene core-shell microspheres was calculated to be approximately 25 nm.

[0062] (3) Preparation of silica@porous polymer core-shell microspheres

[0063] Take 0.1 g of titanium dioxide@polystyrene core-shell microspheres from (2), add 40 mL of 0.25% SDS and ultrasonically disperse for 20 min, then add 20 mL of 5% PVA and ultrasonically disperse for 10 min. Stir at 30 ℃ and 280 r / min for 1 hour to obtain a silica gel suspension. Next, disperse 0.01 g BPO, 0.1 mL GMA, 0.1 mL EDMA, and 0.13 mL butyl levulinate in a mixed solution of 20 mL of 0.25% SDS and 10 mL of 5% PVA, and ultrasonically emulsify until uniformly dispersed. Then, at a low speed of 150 r / min, dropwise add the dispersed monomer mixture to the silica gel suspension. React at 30 ℃ for 6 hours. Then, nitrogen gas was purged for 30 minutes, the temperature was raised to 70 °C, and the reaction was continued for 12 hours. The resulting product was centrifuged three times at 2000 rpm with deionized water, then washed with plenty of 60 °C hot water until the filtrate was foam-free. Finally, it was washed once with anhydrous ethanol and dried at 60 °C overnight. The morphology and pore size distribution of the microspheres are characterized as follows: Figure 5-7 The shell thickness is about 100 nm, and the average pore size is 30 nm.

[0064] Example 3

[0065] Take 0.1 g of titanium dioxide@polystyrene core-shell microspheres from Example 2, add 40 mL of 0.25% SDS and ultrasonically disperse for 20 min, then add 20 mL of 5% PVA and ultrasonically disperse for 10 min. Stir at 30 ℃ and 150 r / min for 1 hour to obtain a silica gel suspension. Next, disperse 0.02 g BPO, 0.2 mL GMA, 0.2 mL EDMA, and 0.4 mL butyl levulinate in a mixed solution of 20 mL of 0.25% SDS and 10 mL of 5% PVA, and ultrasonically emulsify until uniformly dispersed. Then, at a low speed of 150 r / min, dropwise add the dispersed monomer mixture to the silica gel suspension. React at 30 ℃ for 6 hours. Nitrogen gas was then purged for 30 minutes, the temperature was raised to 70 °C, and the reaction was continued for 12 hours. The resulting product was centrifuged three times at 2000 rpm with deionized water, then washed with plenty of 60 °C hot water until the filtrate was foam-free. Finally, it was washed once with anhydrous ethanol and dried at 60 °C overnight. The shell thickness was approximately 150 nm, and the average pore size was 40 nm.

[0066] Example 4

[0067] Take 0.1 g of titanium dioxide@polystyrene core-shell microspheres from Example 2, add 40 mL of 0.25% SDS and ultrasonically disperse for 20 min, then add 20 mL of 5% PVA and ultrasonically disperse for 10 min. Stir at 350 r / min for 1 hour at 30 ℃ to obtain a silica gel suspension. Next, disperse 0.03 g BPO, 0.3 mL GMA, 0.3 mL EDMA, and 0.73 mL butyl levulinate in a mixed solution of 20 mL of 0.25% SDS and 10 mL of 5% PVA, and ultrasonically emulsify until uniformly dispersed. Then, at a low speed of 150 r / min, dropwise add the dispersed monomer mixture to the silica gel suspension. React at 30 ℃ for 6 hours. Nitrogen gas was then purged for 30 minutes, the temperature was raised to 70 °C, and the reaction was continued for 12 hours. The resulting product was centrifuged three times at 2000 rpm with deionized water, then washed with plenty of 60 °C hot water until the filtrate was free of foam. Finally, it was washed once with anhydrous ethanol and dried overnight at 60 °C. The shell thickness was approximately 180 nm, and the average pore size was 50 nm.

[0068] Example 5

[0069] Take 0.1 g of titanium dioxide@polystyrene core-shell microspheres from Example 2, add 40 mL of 0.25% SDS and ultrasonically disperse for 20 min, then add 20 mL of 5% PVA and ultrasonically disperse for 10 min. Stir at 300 r / min for 1 hour at 30 ℃ to obtain a silica gel suspension. Next, disperse 0.04 g BPO, 0.4 mL GMA, 0.4 mL EDMA, and 1.2 mL butyl levulinate in a mixed solution of 20 mL of 0.25% SDS and 10 mL of 5% PVA, and ultrasonically emulsify until uniformly dispersed. Then, at a low speed of 150 r / min, dropwise add the dispersed monomer mixture to the silica gel suspension. React at 30 ℃ for 6 hours. Nitrogen gas was then purged for 30 minutes, the temperature was raised to 70 °C, and the reaction was continued for 12 hours. The resulting product was centrifuged three times at 2000 rpm with deionized water, then washed with plenty of 60 °C hot water until the filtrate was foam-free. Finally, it was washed once with anhydrous ethanol and dried at 60 °C overnight. The shell thickness was approximately 200 nm, and the average pore size was 60 nm.

[0070] 2. Acid and alkali resistance of titanium dioxide@porous polymer core-shell microspheres as chromatographic stationary phase

[0071] Experimental Example 1

[0072] 2 g of titanium dioxide@porous polymer core-shell microspheres were dispersed in isopropanol solution and ultrasonically dispersed for 5 min. The dispersed homogenate was transferred to a column packer and a mixed solution of isopropanol and methanol was used as the displacement solution for column packing. The pressure was maintained at 60 MPa for one hour and then slowly decreased.

[0073] Acid resistance testing was performed on a Shimadzu LC-20 high-performance liquid chromatograph. Isopropanol and water were mixed in equal volumes, and the pH was adjusted to 1. Using this mixture as the mobile phase, the solution was washed for 10 hours at a flow rate of 1 mL / min. The stationary phase was then ejected and tested using transmission electron microscopy. The results are shown in the figure. Figure 8 After prolonged rinsing at high acidity and high flow rate, the morphology of the stationary phase did not change, proving that the material has good acid resistance.

[0074] Experimental Example 2

[0075] The column loading process is as described in Experiment Example 1.

[0076] Alkali resistance testing was performed on a Shimadzu LC-20 high-performance liquid chromatograph. Isopropanol and water were mixed in equal volumes, and the pH was adjusted to 14. Using this mixture as the mobile phase, the solution was washed for 10 hours at a flow rate of 1 mL / min. The stationary phase was then ejected and analyzed using transmission electron microscopy. The results are shown in the figure. Figure 9 After prolonged rinsing at high alkalinity and high flow rate, the morphology of the stationary phase did not change, proving that the material has good alkali resistance.

[0077] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. It should be noted that for those skilled in the art and any person skilled in the art, any equivalent substitutions or changes made to the technical solution and inventive concept of the present invention without departing from the overall concept of the present invention, as well as any changes and improvements made, should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres, characterized in that: Comprising the following steps, (1) Preparation of titanium dioxide@polystyrene core-shell microspheres Micron-sized monodisperse titanium dioxide@polystyrene core-shell microspheres are prepared by dispersion polymerization, with non-porous titanium dioxide microspheres as the core, styrene and 2-vinylbenzene as monomers, sodium p-styrenesulfonate and 3-(methacryloyloxy)propyltrimethoxysilane as auxiliaries, and potassium persulfate as an initiator, wherein the volume ratio of 2-vinylbenzene to styrene is 1:9~2:8; (2) Preparation of titanium dioxide@porous polymer core-shell microspheres Titanium dioxide@polystyrene core-shell microspheres are used as parent spheres, and a seed swelling method is used to uniformly absorb an emulsion containing functional monomers, cross-linking agents and pore-forming agents into the polystyrene shell, and a polymerization reaction is initiated in the presence of a surfactant to obtain titanium dioxide@porous polymer core-shell microspheres by removing the pore-forming agents in the product. 2.The method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres according to claim 1, characterized in that: In step (2), glycidyl methacrylate is used as a monomer, ethylene glycol dimethacrylate is used as a cross-linking agent, and butyl acetoacetate is used as a pore-forming agent, and the surfactant includes polyvinyl alcohol and sodium dodecyl sulfate, the mass percentage concentration of polyvinyl alcohol is 5 %, and the mass percentage concentration of sodium dodecyl sulfate is 0.25 %. 3.The method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres according to claim 2, characterized in that: In step (2), 0.1 g of titanium dioxide@polystyrene core-shell microspheres is weighed into a 100 ml three-necked flask, 10-40 ml of SDS solution is added, ultrasonic dispersion is performed for 20-60 min, then 5-20 ml of PVA is added and ultrasonic dispersion is performed for 10-20 min, then the mixture is placed in a 30℃ water bath and stirred at a speed of 150-350 r / min for 1 hour; then 0.01-0.04 g of BPO, 0.1-0.4 ml of GMA, 0.1-0.4 ml of EDMA, 0.13-1.2 ml of butyl acetoacetate, 10-40 ml of SDS, and 5-20 ml of PVA are ultrasonically mixed until uniform, and then added dropwise to the above solution, and stirred in a 30℃ water bath for 6 hours; then the temperature is raised to 70℃ under nitrogen protection, and stirring reaction is performed for 12 hours; after the reaction is completed, the obtained product is centrifuged three times at 2000 rpm using deionized water, then washed with a large amount of 60℃ hot water until the filtrate is free of foam, and finally washed once with anhydrous ethanol, and then placed in a vacuum drying oven at 60℃ for 12 hours. 4.The method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres according to claim 1, characterized in that: In step (1), non-porous titanium dioxide microspheres TiO2 are dispersed in an ethanol solution in a three-necked flask, ultrasonic nitrogen charging is performed, then potassium persulfate, sodium p-styrenesulfonate and 3-(methacryloyloxy)propyltrimethoxysilane are added, stirring is performed at a speed of 300-500 r / min while heating, after the solution temperature reaches 70℃, 0.8-0.9 ml of styrene and 0.1-0.2 ml of divinylbenzene are dispersed uniformly using anhydrous ethanol, and then slowly added dropwise to the three-necked flask using a dropper, and then stirred at 70℃ for 12 hours; after the reaction is completed, washed with anhydrous ethanol until the solution is clear and no small particles are observed under a microscope, and then placed in a 60℃ constant-temperature oven for drying for 12 hours. 5.The method for preparing acid and alkali resistant core-shell titanium dioxide@porous polymer microspheres according to claim 1, characterized in that: In the step (1), the monodisperse non-porous titanium dioxide microspheres are prepared by the following steps: in a stober system, using an alkyl alcohol as a solvent, a titanate as a titanium source, and an electrolyte as a particle size regulator, monodisperse non-porous titanium dioxide microspheres with controllable particle sizes are prepared by a sol-gel process, and the electrolyte is NaCl, KCl, or LiCl.

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