Polyvinyl alcohol magnetic microsphere as well as preparation method and application thereof

Abstract

The invention discloses polyvinyl alcohol magnetic microspheres as well as a preparation method and application thereof, and the preparation method comprises the following steps: introducing nitrogen to completely react silicon-based magnetic microspheres and monomers in the presence of a cross-linking agent, a surfactant 1 and an initiator, and then adding alkali liquor into a reaction system for hydrolysis reaction to prepare the polyvinyl alcohol magnetic microspheres, wherein the monomer is vinyl acetate or a combination of vinyl acetate and methyl methacrylate. According to the method, high-efficiency preparation of the microspheres can be realized through simple operation steps under the condition that expensive equipment is not needed. The magnetic microspheres prepared by the method have good anti-interference performance, have wide application prospects in multiple fields such as biomedical research, clinical diagnosis and drug carriers, and are expected to promote the development of an in-vitro diagnosis technology especially in the aspect of nucleic acid extraction effect.

Description

Technical Field

[0001] The invention relates to magnetic microspheres, in particular to polyvinyl alcohol magnetic microspheres, a preparation method and application thereof. Background Art

[0002] Polyvinyl alcohol (PVA) is a water-soluble polymer known for its biosafety and biodegradability. The molecular chain of polyvinyl alcohol is rich in hydroxyl groups, which not only enhances its stability in aqueous environments, but also provides abundant reaction sites for further chemical modification. Polyvinyl alcohol can be used in many fields due to its good biocompatibility and adjustable hydroxyl content.

[0003] In the fields of biomedicine and materials science, magnetic microspheres have attracted widespread attention due to their unique physical and chemical properties. There are many different types of magnetic microspheres. Through physical or chemical methods, magnetic nanoparticles can be embedded in the PVA matrix to form polyvinyl alcohol magnetic microspheres. Based on its excellent biocompatibility, adjustable chemical functionality and magnetic manipulation, it has shown application potential in many fields. In drug delivery systems, it can achieve precise control and targeted release of drugs, reduce drug side effects and improve efficacy; in cell separation technology, it can efficiently separate and enrich specific types of cells to provide support for cell therapy and tissue engineering; in environmental governance, polyvinyl alcohol magnetic microspheres can be used to adsorb and remove pollutants in water bodies, such as heavy metal ions and organic pollutants.

[0004] The traditional method for preparing polyvinyl alcohol magnetic microspheres has some limitations, such as: the particle size and distribution of the microspheres cannot be accurately controlled, resulting in limited efficiency and consistency during application; the particle size of the microspheres is large, usually in the micron level, and if microspheres below 100 μm are to be prepared, a high speed of more than 10,000 rpm is required, which places higher requirements on the equipment. Therefore, if this process is used to prepare polyvinyl alcohol magnetic microspheres, it may be difficult to meet the use requirements in certain fields, such as cell sorting, nucleic acid extraction, etc. In order to meet the use requirements in certain aspects, it is particularly urgent to develop an improved polyvinyl alcohol magnetic microsphere. Summary of the invention

[0005] Based on this, the purpose of the present application is to provide a polyvinyl alcohol magnetic microsphere, a preparation method and its application. The polyvinyl alcohol magnetic microspheres prepared by this method can achieve adjustable alcoholysis degree, adjustable carboxyl density, monodispersity and controllable particle size, and achieve precise control of the microsphere particle size in the range of 200nm to 3μm, while maintaining a low CV value, thereby significantly improving its performance and effect in the target application.

[0006] In order to achieve the above objectives, this application provides the following technical solutions:

[0007] In a first aspect, the present invention discloses a method for preparing polyvinyl alcohol magnetic microspheres, comprising the following steps:

[0008] After the silicon-based magnetic microspheres and the monomers are reacted completely by passing nitrogen in the presence of a crosslinking agent, a surfactant 1 and an initiator, an alkali solution is added to the reaction system for hydrolysis reaction to obtain polyvinyl alcohol magnetic microspheres;

[0009] Wherein, the monomer is vinyl acetate or a combination of vinyl acetate and methyl methacrylate.

[0010] Furthermore, the preparation method of the silicon-based magnetic microspheres is as follows:

[0011] (1) adding iron salt and alkali to the reaction solution and mixing them evenly, and reacting them in a closed reactor to obtain magnetic particles;

[0012] (2) reacting the prepared magnetic particles with a silane coupling agent to obtain monodisperse silicon-based magnetic microspheres;

[0013] Furthermore, a surfactant 2 is added to the reaction system of step (1), and the surfactant 2 is one or more of polyacrylic acid, sodium citrate, polyethylene glycol, and polyvinyl pyrrolidone; and the concentration of the surfactant 2 is not higher than 2M.

[0014] Furthermore, the iron salt in step (1) is one or more of ferric chloride hexahydrate, anhydrous ferric chloride or ferric sulfate pentahydrate, and the concentration of iron ions in the reaction system is 0.2 to 0.45 M;

[0015] Further, the reaction solution is water and / or alcohol solution;

[0016] Furthermore, the base is one or more of sodium acetate, sodium acetate dihydrate, sodium hydroxide, and urea, and the molar ratio of the base to iron ions is 2:1 to 6:1.

[0017] Furthermore, the reaction conditions of step (1) are: heating to 160-220° C. at 0.2-2° C. / min and reacting for 8-24 hours.

[0018] Furthermore, the reaction temperature of step (2) is 35-90° C., the pH is 8-11, and the reaction time is 2-6 hours.

[0019] Furthermore, in step (2), the silane coupling agent is one or more combinations of tetraethyl orthosilicate, KH550, KH560, and KH570, and the mass ratio of the silane coupling agent to the magnetic particles is 0.5 to 2:1;

[0020] Preferably, the silane coupling agent is tetraethyl orthosilicate and KH570, and the magnetic particles react with tetraethyl orthosilicate and KH570 in sequence.

[0021] Furthermore, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the reaction conditions are: reacting at 60-90° C. under nitrogen conditions for 2-16 hours.

[0022] Furthermore, in the method for preparing polyvinyl alcohol magnetic microspheres of the present invention, the mass ratio of silicon-based magnetic microspheres to monomers is 1:0.5-2, and the reaction concentration of the monomers is 0.2-1% by volume fraction;

[0023] Furthermore, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the crosslinking agent is one or more of divinylbenzene, N,N'-methylenebisacrylamide, triallyl cyanurate or N-methyldiallylamine, and the molar ratio of the crosslinking agent to the monomer is 1:10 to 4:1;

[0024] Furthermore, in the method for preparing polyvinyl alcohol magnetic microspheres of the present invention, the surfactant 1 is SDS and / or CTAB, and the reaction concentration of the surfactant 1 is 0.1 to 1 g / L;

[0025] Furthermore, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the initiator is one or more of ammonium superphosphate, potassium superphosphate or dibenzoyl peroxide, and the mass ratio of the monomer to the initiator is 1:0.01-0.2.

[0026] In a second aspect, the present invention discloses polyvinyl alcohol magnetic microspheres prepared by the preparation method of the present invention.

[0027] In a third aspect, the present invention discloses the use of the polyvinyl alcohol magnetic microspheres described in the present invention in the preparation of nucleic acid extraction reagents.

[0028] Compared with the prior art, this application has the following beneficial effects:

[0029] The present invention provides an innovative polyvinyl alcohol magnetic microsphere and a preparation method thereof, which can realize efficient preparation of microspheres through simple operation steps without the need for expensive equipment. The magnetic microspheres prepared by the present invention have good anti-interference performance and have broad application prospects in multiple fields such as biomedical research, clinical diagnosis, and drug carriers, especially in terms of nucleic acid extraction effect, and are expected to promote the development of in vitro diagnostic technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the SEM image of the magnetic microspheres prepared in experimental group 1-2 in Example 1.

[0031] Figure 2 SEM image of the magnetic microspheres prepared in experimental group 2-1 in Example 2.

[0032] Figure 3 SEM images of magnetic microspheres prepared in experimental groups 2-4 in Example 2. DETAILED DESCRIPTION

[0033] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0035] In a first aspect, the present invention discloses a method for preparing polyvinyl alcohol magnetic microspheres, comprising the following steps:

[0036] After the silicon-based magnetic microspheres and the monomers are reacted completely by passing nitrogen in the presence of a crosslinking agent, a surfactant 1 and an initiator, an alkali solution is added to the reaction system for hydrolysis reaction to obtain polyvinyl alcohol magnetic microspheres;

[0037] Wherein, the monomer is vinyl acetate or a combination of vinyl acetate and methyl methacrylate;

[0038] The alkali solution includes an alkaline solution capable of exerting a hydrolysis reaction, such as NaOH and the like.

[0039] In certain embodiments, the preparation method of the silicon-based magnetic microspheres is as follows:

[0040] (1) adding iron salt and alkali to the reaction solution and mixing them evenly, and reacting them in a closed reactor to obtain magnetic particles;

[0041] (2) reacting the prepared magnetic particles with a silane coupling agent to obtain monodisperse silicon-based magnetic microspheres;

[0042] In certain embodiments, a surfactant 2 is further added to the reaction system of step (1), and the surfactant 2 is one or more of polyacrylic acid, sodium citrate, polyethylene glycol, and polyvinyl pyrrolidone; and the concentration of the surfactant 2 is not higher than 2M.

[0043] In certain embodiments, the iron salt in step (1) is one or more of ferric chloride hexahydrate, anhydrous ferric chloride or ferric sulfate pentahydrate, and the concentration of iron ions in the reaction system is 0.2 to 0.45 M;

[0044] In certain embodiments, the reaction solution is water and / or an alcohol solution;

[0045] In certain embodiments, the base is one or more of sodium acetate, sodium acetate dihydrate, sodium hydroxide, and urea, and the molar ratio of the base to iron ions is 2:1 to 6:1. The base in step (1) is not completely the same as the alkaline solution used in the hydrolysis reaction above, and can be selected accordingly according to experimental needs.

[0046] In certain embodiments, the reaction conditions of step (1) are: heating to 160-220° C. at 0.2-2° C. / min and reacting for 8-24 hours.

[0047] In certain embodiments, the reaction temperature of step (2) is 35-90° C., the pH is 8-11, and the reaction time is 2-6 h.

[0048] In certain embodiments, the silane coupling agent in step (2) is one or more combinations of tetraethyl orthosilicate, KH550, KH560, and KH570, and the mass ratio of the silane coupling agent to the magnetic particles is 0.5 to 2:1;

[0049] In certain embodiments, the silane coupling agent is tetraethyl orthosilicate and KH570, and the magnetic particles react with tetraethyl orthosilicate and KH570 in sequence.

[0050] In certain embodiments, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the reaction conditions are: reacting at 60-90° C. for 2-16 hours under nitrogen conditions.

[0051] In certain embodiments, in the method for preparing polyvinyl alcohol magnetic microspheres of the present invention, the mass ratio of silicon-based magnetic microspheres to monomers is 1:0.5-2, and the reaction concentration of the monomers is 0.2-1% by volume fraction;

[0052] In certain embodiments, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the crosslinking agent is one or more of divinylbenzene, N,N'-methylenebisacrylamide, triallyl cyanurate or N-methyldiallylamine, and the molar ratio of the crosslinking agent to the monomer is 1:10 to 4:1;

[0053] In certain embodiments, in the method for preparing polyvinyl alcohol magnetic microspheres of the present invention, the surfactant 1 is SDS and / or CTAB, and the reaction concentration of the surfactant 1 is 0.1 to 1 g / L;

[0054] In certain embodiments, in the method for preparing polyvinyl alcohol magnetic microspheres described in the present invention, the initiator is one or more of ammonium superphosphate, potassium superphosphate or dibenzoyl peroxide, and the mass ratio of the monomer to the initiator is 1:0.01 to 0.2.

[0055] In a second aspect, the present invention discloses polyvinyl alcohol magnetic microspheres prepared by the preparation method of the present invention.

[0056] In a third aspect, the present invention discloses the use of the polyvinyl alcohol magnetic microspheres described in the present invention in the preparation of nucleic acid extraction reagents.

[0057] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0058] The present application is described in detail below in conjunction with specific embodiments. These embodiments and comparative examples are used to understand rather than limit the present application.

[0059] Example 1 Preparation of magnetic particles of different particle sizes by adjusting the water content or reaction temperature

[0060] 171 g of ethylene glycol, 23.06 g of anhydrous sodium acetate, ferric chloride hexahydrate, anhydrous ferric chloride and water were added to a beaker, and the iron ion concentration was controlled to be 0.36 M. The mixed solution was evenly divided into multiple portions to set up different experimental groups. The volume fraction of water and the reaction temperature of each experimental group were shown in Table 1. After reacting for 24 hours, the magnetic particles were washed with pure water to obtain magnetic particles.

[0061] Table 1 shows the particle size changes of magnetic particles prepared under different conditions (the particle size is measured by the following method: taking SEM images of 50 magnetic particles, measuring the particle size at randomly selected positions, and calculating the average particle size). It can be concluded from Table 1 that the particle size of the magnetic particles can be controlled by adjusting the content of water molecules or the reaction temperature. Figure 1 This is a scanning electron microscope image (SEM image) of the magnetic particles prepared in group No. 1-2.

[0062] Table 1

[0063]

[0064] Example 2 Preparation of magnetic particles of different particle sizes and morphologies by adjusting the type of surfactant 2

[0065] Add 570g of ethylene glycol, 46.05g of alkali, and 50.6g of ferric chloride hexahydrate into a beaker, add different types of surfactants 2 to 0.5%wt of the reaction system according to Table 2, mix well and transfer to a hydrothermal reactor and set it to 200°C for reaction for 24h, and wash with pure water after the reaction to obtain magnetic particles. It can be concluded from Table 2 that under the same conditions, different types of surfactants are used to participate in the reaction to obtain magnetic particles of different particle sizes. Figure 2 This is the SEM image of the magnetic particles in the experimental group No. 2-1. Figure 3 The SEM images of the magnetic particles in the experimental groups No. 2-4 are shown in Figure 2. Figure 2 and Figure 3 It can be seen that the morphologies of magnetic particles prepared using polyacrylic acid and polyvinyl pyrrolidone as surfactants are different. The magnetic particles prepared using polyacrylic acid as a surfactant are solid microspheres, and the magnetic particles prepared using polyvinyl pyrrolidone as a surfactant are hollow microspheres. Microspheres with different particle sizes and morphologies can be prepared according to different application requirements.

[0066] Table 2

[0067]

[0068] Example 3 Preparation of polyvinyl alcohol magnetic microspheres

[0069] Take 1g of 455nm magnetic particles of No. 1-7 in Example 1, add 100mL of 1M hydrochloric acid, stir ultrasonically for 10min, and then wash with pure water 5 times; add 800g of pure water and 1g of tetraethyl silicate, stir ultrasonically for 10min, add 20mL of ammonia water, react for 3h, and then wash with pure water. Re-disperse the magnetic particles in 800g of pure water, add 10g of KH570, stir ultrasonically for 10min, add 20mL of ammonia water, react for 3h, and then wash with ethanol 3 times and pure water 3 times to obtain silicon-based magnetic microspheres.

[0070] Silica-based magnetic microspheres were mixed evenly with 0.75 g of CTAB, 250 g of water, 25 mL of divinylbenzene, 7.5 mL of n-butanol, and 1.25 g of vinyl acetate. The mixture was heated and stirred under nitrogen. BPO was added at 80°C to react for 8 h. After the reaction, 10 g of NaOH was added and the reaction was continued for 1 h. The mixture was washed three times with ethanol and then washed with pure water to obtain polyvinyl alcohol magnetic microspheres.

[0071] Example 4

[0072] The preparation conditions of Example 4 are substantially the same as those of Example 3, except that the monomer in Example 4 further includes 0.2 g of methyl methacrylate.

[0073] Example 5

[0074] The preparation conditions of Example 5 are substantially the same as those of Example 3, except that the monomer in Example 5 further includes 0.4 g of methyl methacrylate.

[0075] Example 6

[0076] The preparation conditions of Example 6 are basically the same as those of Example 3, except that the magnetic particles used in Example 6 are the magnetic particles prepared by sequence number 2-1 in Example 2.

[0077] Example 7

[0078] The preparation conditions of Example 7 are basically the same as those of Example 3, except that the magnetic particles used in Example 7 are the magnetic particles prepared by sequence numbers 2-4 in Example 2.

[0079] Table 3

[0080] Serial number Magnetic particles Vinyl acetate Methyl Methacrylate Example 3 Examples 1-7 1.25g 0g Example 4 Examples 1-7 1.25g 0.2g Example 5 Examples 1-7 1.25g 0.4g Example 6 Example 2-1 1.25g 0g Example 7 Embodiment 2-4 1.25g 0g

[0081] Comparative Example 1

[0082] The preparation conditions of Comparative Example 1 and Example 3 are basically the same, except that: Comparative Example 1 prepares silicon-based magnetic microspheres without the subsequent monomer polymerization step.

[0083] Comparative Example 2

[0084] The silicon-modified magnetic microspheres prepared in Example 3 were modified with PVA. The specific steps were as follows: adding the silicon-modified magnetic microspheres to 100 mL of pure water, adding 100 mL of 5% PVA solution, stirring at 65° C. for 4 h, and washing with pure water 5 times after the reaction was completed.

[0085] Comparative Example 3

[0086] The silicon-based magnetic microspheres prepared in Example 7 were modified with PVA. The specific steps were as follows: adding the silicon-based modified magnetic microspheres to 100 mL of pure water, adding 100 mL of 5% PVA solution, stirring at 65° C. for 4 h, and washing with pure water 5 times after the reaction was completed.

[0087] Dynamic light scattering (DLS) was used to measure the hydrated particle size of Example 3 and Comparative Examples 1-3. The hydrated particle size was used to represent the degree of agglomeration of the magnetic microspheres. From the DLS test data (Table 4), it can be seen that Comparative Example 1 did not perform monomer polymerization on the silicon-based magnetic microspheres, and its hydrated particle size was slightly different from that of Example 3. Comparative Examples 2 and 3 were prepared using PVA, and the hydrated particle size was significantly increased, showing serious agglomeration, which exceeded the upper limit of the equipment test (1000 nm), and the data did not have much reference significance.

[0088] Table 4

[0089] Test items Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 DLS particle size (nm) 603 615 12025 5450

[0090] Nucleic acid extraction performance test

[0091] A kit (purchased from Fosun Diagnostics Technology (Shanghai) Co., Ltd.) was used to perform HBV virus extraction test. The positions of the kit plates are shown in Table 5 (except for the magnetic bead aqueous solution, all other reagents in Table 5 are reagents in the kit). The specific test process is as follows (refer to the instruction manual of the kit):

[0092] a. Use human serum to dilute the HBV virus quality control provided by the kit as the extraction sample, and take serum and

[0093] HBV virus quality control products were mixed and added to blood as control extraction samples;

[0094] b. Take 200 μL of sample and add it to columns 1 and 7, and take 30 μL of 25 mg / mL magnetic bead aqueous solution and add it to columns 2 and 8; the magnetic bead aqueous solution is the magnetic microsphere product of Example 3-7 and Comparative Example 1-3, and each magnetic microsphere product was subjected to nucleic acid extraction experiments and performance tests;

[0095] c. Use a 16-channel nucleic acid extractor and the product provided procedures to extract nucleic acids;

[0096] d. Perform amplification test on the eluate using PCR amplification.

[0097] Table 5

[0098]

[0099] Serum and serum + blood were used as samples respectively, and the CT value of the extracted nucleic acid was measured to measure the ability of magnetic beads to resist hemoglobin interference in blood sample detection. It is generally believed in the art that a difference of <0.3CT is a test fluctuation, a difference of 0.5CT is the upper limit of the fluctuation of quality inspection, and a difference of 1CT indicates that the performance of nucleic acid extraction reagents is greatly different.

[0100] The test results of nucleic acid extraction are shown in Table 6, from which it can be concluded that: (1) For the magnetic microspheres prepared in Examples 3-7, the CT difference of nucleic acid extraction in serum and serum + blood samples is within the range of less than 0.3, and the test results are stable, which shows that the magnetic microspheres prepared in Examples 3-7 have strong anti-heme interference ability. (2) The magnetic microspheres of Comparative Example 1 show excellent nucleic acid extraction performance in serum samples, but in serum + blood samples, the extraction effect of nucleic acid is significantly reduced, which shows that the magnetic microspheres of Comparative Example 1 have weak anti-heme interference ability. (3) The magnetic microspheres prepared in Comparative Examples 2-3 have poorer nucleic acid extraction performance in serum samples than that of Examples 3-7. In serum + blood samples, the detection difference of CT value is higher than 0.5, which shows that the magnetic microspheres of Comparative Examples 2-3 have poor nucleic acid extraction performance and weak anti-heme interference ability.

[0101] Table 6

[0102]

[0103] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims, and the description and drawings may be used to interpret the contents of the claims.

Claims

1. A method for preparing polyvinyl alcohol magnetic microspheres, characterized in that: The following steps are involved: After the silicon-based magnetic microspheres and the monomers are reacted completely by passing nitrogen in the presence of a crosslinking agent, a surfactant 1 and an initiator, an alkali solution is added to the reaction system for hydrolysis reaction to obtain polyvinyl alcohol magnetic microspheres; Wherein, the monomer is vinyl acetate or a combination of vinyl acetate and methyl methacrylate.

2. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 1, characterized in that: The preparation method of the silicon-based magnetic microspheres is as follows: (1) adding iron salt and alkali to the reaction solution and mixing them evenly, and reacting them in a closed reactor to obtain magnetic particles; (2) reacting the prepared magnetic particles with a silane coupling agent to obtain monodisperse silicon-based magnetic microspheres; Furthermore, a surfactant 2 is added to the reaction system of step (1), and the surfactant 2 is one or more of polyacrylic acid, sodium citrate, polyethylene glycol, and polyvinyl pyrrolidone; and the concentration of the surfactant 2 is not higher than 2M.

3. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 2, characterized in that: The iron salt in step (1) is one or more of ferric chloride hexahydrate, anhydrous ferric chloride or ferric sulfate pentahydrate, and the concentration of iron ions in the reaction system is 0.2-0.45M.

4. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 2, characterized in that: The reaction conditions of step (1) are: heating to 160-220° C. at 0.2-2° C. / min and reacting for 8-24 hours; the reaction temperature of step (2) is 35-90° C., pH is 8-11, and the reaction time is 2-6 hours.

5. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 2, characterized in that: The silane coupling agent is one or more combinations of tetraethyl orthosilicate, KH550, KH560, and KH570, and the mass ratio of the silane coupling agent to the magnetic particles is 0.5 to 2:1; Preferably, the silane coupling agent is tetraethyl orthosilicate and KH570, and the magnetic particles react with tetraethyl orthosilicate and KH570 in sequence.

6. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 1, characterized in that: The reaction conditions are: react at 60-90°C for 2-16 hours under nitrogen.

7. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 1, characterized in that: The mass ratio of silicon-based magnetic microspheres to monomers is 1:0.5-2, and the reaction concentration of the monomers is 0.2-1% by volume fraction.

8. The method for preparing polyvinyl alcohol magnetic microspheres according to claim 1, characterized in that: The crosslinking agent is one or more of divinylbenzene, N,N'-methylenebisacrylamide, triallyl cyanurate or N-methyldiallylamine, and the molar ratio of the crosslinking agent to the monomer is 1:10 to 4:1; The surfactant 1 is SDS and / or CTAB, and the reaction concentration of the surfactant 1 is 0.1-1 g / L; The initiator is one or more of ammonium superphosphate, potassium superphosphate or dibenzoyl peroxide, and the mass ratio of the monomer to the initiator is 1:0.01-0.

2.

9. Polyvinyl alcohol magnetic microspheres obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the polyvinyl alcohol magnetic microspheres according to claim 9 in preparing nucleic acid extraction reagents.

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