Macroporous silicon dioxide microsphere as well as preparation method and application thereof

Abstract

The invention discloses macroporous silicon dioxide microspheres as well as a preparation method and application thereof, and belongs to the technical field of nano high-tech materials. The main aperture of the silicon dioxide microsphere is about 100nm, the primary particle size is 50nm, the agglomerated particle size D50 is 100mu m, and the specific surface area is gt; the pore volume is 1.0 to 1.75 cm / g. According to the preparation method, rice hull-based high-purity sodium silicate with the modulus of 3.25 and carbon dioxide are used as main raw materials, and the designed core technology is that a double-template system composed of polystyrene microspheres and a macromolecular block copolymer is adopted, and under specific conditions, processes such as carbon dioxide carbonization gel, spray drying granulation, oil-phase thermocuring and programmed roasting are used. The rice hull-based green high-tech material obtained by the method has the advantages of mild reaction process, good controllability of aperture and particle size, and high mechanical strength of the product. The macroporous silica microspheres prepared by the method are particularly suitable for the fields of drug controlled release systems, biological macromolecule chromatographic separation, immobilized enzyme carriers, high-performance catalyst carriers and the like.

Description

Technical Field

[0001] This invention relates to the field of nanomaterials technology, specifically to a macroporous silica microsphere, its preparation method, and its application. Background Technology

[0002] Silica materials with large pore sizes possess characteristics such as specific surface area, chemical stability, ease of surface modification, and biocompatibility, making them widely used in drug delivery, catalysis, chromatographic separation, and bioengineering. The key technical parameters are the pore size, pore volume, and particle size of silica.

[0003] Traditional silica gel chromatography packing materials typically have pore sizes less than 30 nm, resulting in low efficiency for the separation and purification of biomolecules such as proteins, antibodies, viruses, and plasmid DNA. This invention develops macroporous silica microbeads with pore sizes of approximately 100 nm, effectively solving this problem and allowing biomolecules to rapidly diffuse to all active sites within the pores. The 100-micron particle size (range 80-130 μm) provides excellent hydrodynamic performance, making it suitable for preparing low-pressure, high-capacity preparative chromatography columns.

[0004] Currently, commonly used template agents include small-molecule surfactants for preparing mesoporous materials and polymer microspheres for preparing macroporous materials. In the preparation of macroporous silica materials, a sol-gel method combined with template technology is often employed. This technology has serious drawbacks. For example, using a single template agent makes it difficult to simultaneously and precisely control the macropore size of 100 nm and the high pore volume of >1.0 cm³ / g. Complex molding processes are required to barely achieve microspheres around 100 μm in size. The microspheres exhibit large particle size deviations and insufficient strength, often necessitating high-temperature sintering, which can lead to the collapse or shrinkage of the macroporous structure. Furthermore, these methods often use organosilicon sources such as tetraethyl orthosilicate and strong acids, resulting in high costs and environmental unfriendliness.

[0005] Therefore, designing and developing a silica microsphere with characteristics such as green bio-based, low cost, specific large pore size, narrow particle size distribution, high pore volume, and sufficient mechanical strength would have significant industrial value. Summary of the Invention

[0006] The first objective of this invention is to address the shortcomings of existing macroporous silica lenticular beads technology and provide macroporous silica lenticular beads with a pore size D50 of 100nm (range 90-110nm), a particle size D50 of 100um (range 80-130um), high porosity, sphericity greater than 0.9, and a particle size distribution variation coefficient (CV value) of less than 15%.

[0007] The second objective of this invention is to provide a method for preparing the above-mentioned macroporous microspheres. This method uses inexpensive rice husk-based sodium silicate and carbon dioxide as the main raw materials. The raw materials are green, the pore size and particle size are controllable, and the product has high strength.

[0008] The third objective of this invention is to provide the application of the aforementioned macroporous microspheres in the field of high-end separation and catalysis.

[0009] To achieve the above three objectives, the technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides macroporous silica microspheres with an average particle size between 80-130 micrometers (D50=100um), a pore size between 90-110 nanometers (D50=100nm), a specific surface area greater than 25 m² / g, and a pore volume of 1.0-1.75 cm³ / g. Preferably, the microspheres have good sphericity and uniform particle size distribution.

[0011] Secondly, the present invention provides a method for preparing the above-mentioned macroporous silica microspheres, the specific steps of which are as follows:

[0012] S1. Preparation of a sodium silicate solution containing dual template agents: Dilute sodium silicate with a modulus of 3.25 with deionized water to a SiO2 concentration of 68 wt%. Add polystyrene (PS) microspheres with a particle size between 95-120 nm as the primary template agent for pore formation, and add polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer (such as P123) as an auxiliary template agent and structure directing agent. Add sodium polyacrylate dispersant to prevent PS agglomeration. Adjust the pH value to between 10.5 and 11.0 with dilute acid or ion exchange resin. After thorough stirring, a homogeneous and stable mixed solution is formed.

[0013] S2. Carbon Dioxide Acidification-Induced Gelation: In a temperature-controlled reactor, maintain the temperature between 25-30°C. Slowly and uniformly introduce CO2 gas from the bottom of the reactor into the mixed solution from step S1, ensuring uniform acidification and a slow, steady decrease in the pH value of the mixed solution. When the pH value drops to 9.5, stop the gas flow and allow the system to stand, allowing the initially formed silica species to assemble around the template. Then continue the gas flow. When the pH value approaches the 7.0-8.0 range, the system reacts rapidly, forming a silica gel network with a dual-template framework. Maintain these conditions for maturation.

[0014] S3. Spray drying granulation: The gel produced after S2 curing is broken up, and the solid content is adjusted to between 15-20%, preferably 18%. A small amount of binder is added, preferably hydroxypropyl methylcellulose. The mixture is dried and granulated using a centrifugal spray dryer at an inlet air temperature of 180°C and an atomizer speed of 15,000-20,000 rpm to obtain relatively regular spherical precursor silica microspheres.

[0015] S4. Oil-phase thermosetting: The silica microspheres obtained in S3 are dispersed in a silicone oil medium and subjected to programmed temperature rise heating treatment. This process will further condense and strengthen the gel network, and the liquid in the gel network will continue to overflow. This process can significantly improve the mechanical strength of the silica microspheres. At the same time, under the protection of the oil phase environment, the capillary force damage to the pore structure caused by the drying of the aqueous phase is avoided. During this process, the particle size and pore size of silica will decrease slightly, and the sphericity will be improved.

[0016] S5. Template Removal and Pore Structure Forming: The silica microspheres cured in S4 are subjected to precisely controlled programmed temperature calcination. At 350°C, organic materials such as P123 and HPMC are removed. At 500°C, the PS microsphere template is completely decomposed and removed, replicating the spherical pores of the PS template to form the final macroporous structure that meets the requirements. During this process, the silica particle size and pore size will slightly decrease. It is necessary to control the heating rate and atmosphere to stabilize the pore wall structure and prevent collapse. High temperatures further ensure that the sphericity of the silica microspheres is greater than 0.9 and the coefficient of variation (CV) of the particle size distribution is less than 15%.

[0017] Thirdly, the present invention provides specific applications of the macroporous silica microspheres in the fields of biochromatographic separation media, immobilized enzyme carriers, drug controlled-release carriers, and macromolecular reaction catalyst carriers.

[0018] Products and others prepared using the method of this invention:

[0019] NO.1. The technical parameters of the prepared product meet the design goals: The prepared silica microspheres simultaneously possess a large pore size of D50=100nm, a suitable particle size of D50=80-130 micrometers, high pore volume, and good sphericity and mechanical strength, making them particularly suitable for the separation and catalysis of biomacromolecules.

[0020] NO.2. Mild and Green Economic Process: Using rice husk-based sodium silicate and CO2 as the main raw materials, this process replaces expensive organosilicon sources such as TEOS and strong acids. The byproduct is sodium carbonate, which can be recycled as alkali solution during the rice husk ash alkalization process. If the alkalinity is insufficient, a certain amount of sodium hydroxide can be added to supplement OH ions. This process conforms to the principles of green chemistry. For details of this sodium carbonate recycling process, please refer to the invention "A method for preparing rice husk-based high-purity high-modulus sodium silicate solution", application number or patent number: 202511260696.6 submitted by our company.

[0021] NO.3. Dual controllability of pore size and particle size: The final pore size is precisely controlled by selecting PS microspheres with a specific particle size (slightly larger than the pore size of silica macropores); the product particle size is controlled by adjusting the atomization speed and feed concentration of the spray drying process, resulting in good process compatibility.

[0022] NO.4. High structural mechanical strength: The innovative and precisely controlled "oil phase thermosetting" step effectively enhances the mechanical properties of the gel network, enabling the macroporous thin-walled structure to remain intact and not easily broken during subsequent processing and practical applications.

[0023] NO.5. Pore structure optimization: The synergistic use of dual template agents not only forms regular main channels of about 100nm (from PS), but also fills and connects the gaps between them with smaller mesopores generated by the P123 template, ensuring high porosity and high specific surface area, enhancing the connectivity of the channels, and ensuring the integrity of the silica microspheres and making them less prone to breakage. Attached Figure Description

[0024] Figure 1 is a SEM image of the silica microspheres prepared in Example 1 of the present invention: scale bar: 100 μm.

[0025] Figure 2 is a high-magnification SEM image of the surface of a single microbead in Figure 1. Scale bar: 5 μm.

[0026] Figure 3 shows the nitrogen adsorption-reference method graph and numerical photographs of the silica microspheres prepared in Example 1 of this invention. Sample 1 and Sample 3 in the figure are silica microspheres prepared in Example 1 of this invention. The standard sample and Sample 2 are silica standard samples used for comparing the accuracy of the standard sample and the detection value. Based on the specific surface area of ​​28 m² / g and the aggregate particle size D50 of the silica microspheres of 105 μm (measured by SEM in Figures 1 and 2), the original particle size of the silica microspheres can be calculated using a general formula to be around 50 nm, the average pore size between 90-130 nm, and the pore volume between 1.0-1.4 cm³ / g. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited thereto.

[0028] Example 1

[0029] Preparation of macroporous silica microspheres:

[0030] S1. Solution Preparation: Take 100g of rice husk-based sodium silicate with a modulus of 3.25 and prepare a solution with a SiO2 content of 28.5wt%. Dilute with deionized water to a total mass of 500g, at which point the SiO2 concentration is approximately 5.7wt%. Add 75g of monodisperse polystyrene microsphere emulsion with an average particle size of approximately 105nm, of which the solid content is 20%, i.e., the PS solid mass is 15g, approximately 52.6% of the theoretical SiO2 mass of 28.5g. In actual production, this can be adjusted according to the claims. Then add 3g of P123 and 2.5g of sodium polyacrylate. Treat part of the solution with a cation exchange resin column to reduce the sodium ion concentration, while adjusting the pH value to 10.8, and gently stir mechanically for 3 hours.

[0031] S2. Carbon dioxide acidification and gelation: The solution prepared in S1 was placed in a 1L jacketed reactor (with a high-power deceleration stirrer), and the temperature was controlled at 28℃. 99.95% pure CO2 gas was then uniformly introduced from the bottom at a flow rate of 0.35 L / min. When the pH reached pH=9.5, the gas flow was stopped, and the mixture was allowed to stand for 30 minutes. Gas flow was then resumed until the pH reached approximately 8.0. The system reacted rapidly, yielding a milky white gel block with a network structure. The CO2 was then quickly shut off, and stirring was stopped after 30 minutes. The mixture was allowed to stand and mature at 28℃ for 60 hours, followed by low-speed stirring for another hour to obtain a stable milky white gel block.

[0032] S3. Spray drying granulation: The gel blocks were broken up using a high-speed disperser, water was added to adjust the solid content to 18%, 0.4g HPMC was added as a binder, and a centrifugal spray dryer was used to control the inlet air temperature at 190℃, the outlet air temperature at 95℃, the atomizing disc speed at 18000 rpm, and the feed rate at 400 mL / min. The qualified white precursor powder was collected by grading and screening.

[0033] S4. Oil phase thermosetting: The precursor powder prepared in S3 was mixed with methyl silicone oil No. 200 at a mass ratio of 1:6 and loaded into a stirred reactor. The temperature was programmed and controlled to rise to 120°C at 12°C / min and held for 12 hours. Then the temperature was raised to 220°C at 0.51°C / min and held for 35 hours. After cooling, the mixture was washed three times with n-hexane to remove the silicone oil and then dried.

[0034] S5. Template Removal: Place the cured powder from S4 in a tube furnace and heat it to 350°C at a rate of 0.51°C / min under a nitrogen atmosphere. Switch to air and hold for 4 hours. Then, heat it to 500°C at a rate of 0.5°C / min, switch to nitrogen containing 13% oxygen, and hold for 6 hours. Then, cool it down to 200°C at a controlled rate of 1°C / min, and finally allow it to cool naturally to room temperature. Pass the powder through a standard grading sieve, collecting particles that pass through a 120-mesh / 125μm sieve and are retained on a 100-mesh / 150μm sieve to obtain the final product.

[0035] Example 2: Chromatographic packing material

[0036] The macroporous silica microspheres obtained in Example 1 were surface-epoxylated with γ-glycidoxypropyltrimethoxysilane and then coupled with Protein A ligand. These microspheres were then packed into a 10 mm inner diameter glass column to form a 10 cm bed height chromatographic column. Sample loading with IgG-containing buffer was tested. The results showed that the dynamic loading capacity (DBC, 10% breakthrough) of this packing material reached 45 mg IgG / mL, which is approximately 30% higher than that of commercially available 30 nm pore size Protein A packing material (DBC approximately 35 mg / mL), and the back pressure increase was gradual.

[0037] Example 3: Immobilized enzyme carrier

[0038] The silica microbeads obtained in Example 1 were aminopropyltriethoxysilane-amined and then immobilized with Candida lipase using glutaraldehyde as a cross-linking agent. The immobilized enzyme activity recovery rate was measured to be 72%, and the enzyme loading was 85 mg / g carrier. When used to catalyze the transesterification reaction of vinyl acetate and n-hexanol, the enzyme activity remained at 88% of the initial value after 10 consecutive batches, demonstrating good operational stability and reusability.

[0039] Comparative example:

[0040] If step S4 is omitted and "oil phase thermosetting" is not performed, and the spray-dried precursor is directly calcined, the remaining steps are the same as in Example 1. The resulting silica microsphere product has poor mechanical strength, and the breakage rate is as high as about 25% during sieving and subsequent column packing. Nitrogen adsorption calculation shows that the pore volume is only 0.85 cm³ / g, which indicates that the pore structure partially collapsed during the direct calcination process.

[0041] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This descriptive method is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A macroporous silica microsphere, its preparation method and application, characterized in that, The characteristics of silica microspheres are: macropore diameter D50=100nm, deviation range 10nm, microsphere particle size D50=100 micrometers, specific surface area greater than 25 m² / g, and pore volume of 1.0-1.75 cm³ / g. The preparation method uses rice husk-based high-purity sodium silicate with modulus 3.25 and carbon dioxide as the main raw materials. Polystyrene microspheres and macromolecular block copolymers form a dual template. Under specific conditions, they are prepared by carbon dioxide carbonization gelation, spray drying granulation, oil phase thermosetting and programmed calcination.

2. The macroporous silica microspheres according to claim 1, characterized in that, The microspheres have a macropore diameter D50 of 100 nm, a sphericity greater than 0.9, and a particle size distribution variation coefficient (CV value) of less than 15%.

3. The preparation method according to claim 1, characterized in that, Includes the following steps: S1. Preparation of a sodium silicate mixed solution containing two template agents: High-purity sodium silicate with a modulus of 3.25 is diluted with water to a SiO2 concentration of 68 wt%. Polystyrene microspheres with a particle size of 95-120 nm are added as the main template agent, and polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer is added as the auxiliary template agent. A dispersant is also added, and the pH value is adjusted to 10.5-11.

0. The mixture is stirred evenly to obtain a mixed solution. The mass of the polystyrene microspheres is about 35% of the theoretical mass of SiO2, and the mass of the block copolymer is about 58% of the theoretical mass of SiO2. S2. Carbonation-induced gelation: At 25-30℃, CO2 gas with a purity of 99.995% or higher is introduced into the mixed solution until the pH value is 7.0-8.

0. During this period, when the pH value drops to 9.5, the solution is allowed to stand for aging. After the reaction is completed, the solution is kept warm for aging to obtain wet silica gel. S3. Spray drying granulation: The wet gel is made into a slurry with a solid content of 15-20%, a binder is added, and the precursor microspheres are obtained by spray drying at 180 degrees and a speed of 15,000-20,000 rpm. S4. Oil phase thermosetting: The prepared precursor microspheres are dispersed in silicone oil and cured by heating. After completion, the silicone oil is washed away. S5. Template removal and pore structure formation: The cured microspheres are heated and calcined according to a predetermined program. The auxiliary template and binder are removed at 350°C, and the polystyrene microsphere template is removed at 500°C to obtain macroporous silica microspheres.

4. The method according to claim 3, characterized in that, In step S1, the dispersant is sodium polyacrylate, and the amount added is 0.5-1.0% of the total mass of the solution; in step S3, the binder is hydroxypropyl methylcellulose, and the amount added is 12% of the mass of SiO2 solids in the slurry.

5. The method according to claim 3, characterized in that, Step S2 specifically includes: introducing CO2 at a flow rate of 0.3-0.5 L / min, stopping the aeration when the pH of the system drops to 9.5, and letting it stand for 30 minutes; continuing the aeration until the pH is between 7.0 and 8.0, and maintaining it at 30°C for 60 hours.

6. The method according to claim 3, characterized in that, In step S4, the programmed temperature rise curing is as follows: the temperature is increased to 120°C at 12°C / min, held for 12 hours, and then increased to 180-250°C at 0.51°C / min, held for 35 hours.

7. The method according to claim 3, characterized in that, In step S5, the programmed temperature rise calcination is carried out under a flowing atmosphere, specifically: the temperature is increased from room temperature to 350°C at a rate of 0.51°C / min, and held at this temperature for 4 hours in an air or nitrogen atmosphere; then the temperature is increased to 500°C at a rate of 0.4-0.6°C / min, and held at this temperature for 6 hours in a nitrogen atmosphere containing 13% oxygen; finally, the temperature is controlled to drop back to room temperature.

8. The method according to any one of claims 3-7, characterized in that, The precursor microspheres obtained in step S3, or the macroporous silica microspheres obtained after step S5, are subjected to multi-stage sieving to collect fractions with a particle size of 80-130 micrometers.

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