Magnetic polystyrene microspheres and preparation method thereof

Abstract

The present invention relates to the field of biomaterial technology, and in particular to magnetic polystyrene microspheres and a method for preparing the same. The method comprises the following steps: providing magnetic nanoparticles, mixing the magnetic nanoparticles, polyethylene glycol, and a solvent, stirring the reaction, and coating the magnetic nanoparticles with the polyethylene glycol to prepare modified magnetic nanoparticles, wherein the polyethylene glycol has a degree of polymerization of 400 to 6000; providing polystyrene seed microspheres, mixing the polystyrene seed microspheres, the modified magnetic nanoparticles, an aqueous solution of sodium lauryl sulfate, and a swelling agent, and utilizing the swelling and contraction of the polystyrene seed microspheres to allow the modified magnetic nanoparticles to enter the polystyrene seed microspheres to prepare magnetic beads; and coating the surface of the magnetic beads with a shell layer. The resulting magnetic polystyrene microspheres have good particle size uniformity, and the magnetic nanoparticles are evenly dispersed within them, and can be used to synthesize fluorescently encoded microspheres.

Description

Technical Field

[0001] The present invention relates to the technical field of biomaterials, and in particular to magnetic polystyrene microspheres and a preparation method thereof. Background Art

[0002] Fluorescently encoded microspheres are loaded with varying amounts of one or more fluorescent dyes with different optical properties, enabling clustering within detection instruments. Magnetic fluorescently encoded microspheres, on the other hand, possess magnetic properties, enabling magnetic sorting. In some sophisticated detection systems, magnetic sorting can significantly improve detection limits by removing unreacted products.

[0003] Magnetic polystyrene microspheres can be used to synthesize fluorescently encoded microspheres. However, conventional methods such as monomer polymerization often produce magnetic polystyrene microspheres with poor particle size uniformity. Furthermore, the magnetic nanoparticles are often unevenly dispersed within the microspheres, resulting in a biased magnetic response. Summary of the Invention

[0004] Based on this, the present invention provides a magnetic polystyrene microsphere and a preparation method thereof.

[0005] The first aspect of the present invention provides a method for preparing magnetic polystyrene microspheres, and the technical solution is as follows:

[0006] A method for preparing magnetic polystyrene microspheres comprises the following steps:

[0007] Providing magnetic nanoparticles, mixing the magnetic nanoparticles, polyethylene glycol and a solvent, stirring and reacting, so that the polyethylene glycol coats the magnetic nanoparticles to prepare modified magnetic nanoparticles, wherein the degree of polymerization of the polyethylene glycol is 400 to 6000;

[0008] Providing polystyrene seed microspheres, mixing the polystyrene seed microspheres, the modified magnetic nanoparticles, an aqueous solution of sodium lauryl sulfate, and a swelling agent, and utilizing the swelling and shrinkage of the polystyrene seed microspheres to allow the modified magnetic nanoparticles to enter the polystyrene seed microspheres to prepare magnetic beads;

[0009] A shell layer is coated on the surface of the magnetic beads.

[0010] In some embodiments, the mass ratio of the magnetic nanoparticles to polyethylene glycol is 1:(5-20).

[0011] In some embodiments, the solvent is ethanol.

[0012] In some embodiments, the stirring reaction to coat the magnetic nanoparticles with polyethylene glycol comprises one or more of the following conditions:

[0013] a) the stirring reaction temperature is 40 to 60° C.; b) the stirring reaction time is 0.5 h to 1 h; c) the stirring reaction speed is 600 rpm to 1000 rpm; and d) the stirring reaction is carried out under a protective atmosphere.

[0014] In some embodiments, the swelling agent includes a good solvent and a poor solvent, and the volume ratio of the good solvent to the poor solvent is 1:(1-20).

[0015] In some embodiments, the good solvent is selected from one or more of dichloromethane, chloroform, petroleum ether and chlorododecane.

[0016] In some embodiments, the poor solvent is selected from one or more of methanol, ethanol and isopropanol.

[0017] In some embodiments, the shell layer is a polystyrene layer.

[0018] In some embodiments, coating the surface of the magnetic beads with the polystyrene layer comprises the following steps:

[0019] Magnetic beads, styrene monomer and a cross-linking agent are mixed, and an initiator is added to cause a polymerization reaction, thereby coating the surface of the magnetic beads with a polystyrene layer.

[0020] In some embodiments, the step of adding a carboxyl compound is further included before the polymerization reaction occurs.

[0021] In some embodiments, the method for preparing polystyrene seed microspheres comprises the following steps:

[0022] Methacrylic acid, styrene monomer and dispersant solution are mixed, an initiator is added, a polymerization reaction occurs, and polystyrene seed microspheres are prepared.

[0023] In some embodiments, the method for preparing the magnetic nanoparticles comprises the following steps:

[0024] Ferric dichloride, ferric chloride and water are mixed, and an alkaline substance is added to react to prepare the magnetic nanoparticles.

[0025] The second aspect of the present invention provides magnetic polystyrene microspheres, which are prepared by the above preparation method.

[0026] Compared with the traditional solution, the present invention has the following beneficial effects:

[0027] The present invention first coats magnetic nanoparticles with polyethylene glycol of a specific degree of polymerization, then uses a swelling method to allow the polyethylene glycol-coated magnetic nanoparticles to enter polystyrene seed microspheres. The polyethylene glycol coating improves the dispersibility of the magnetic nanoparticles, ensuring that they are evenly distributed within the polystyrene seed microspheres after subsequent swelling. The coating shell prevents leakage of the magnetic nanoparticles. The magnetic polystyrene microspheres obtained by this method have good particle size uniformity and evenly dispersed magnetic nanoparticles within, making them suitable for the synthesis of fluorescently encoded microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention and to provide a more complete understanding of the present invention and its beneficial effects, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present application. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0029] Figure 1 Schematic diagram of the synthetic route of step 3 and step 4 of Example 1;

[0030] Figure 2 TEM image of the magnetic polystyrene prepared in Example 1;

[0031] Figure 3 TEM image 2 of the magnetic polystyrene prepared in Example 2

[0032] Figure 4 This is a microscope photograph of the magnetic polystyrene prepared in Example 1;

[0033] Figure 5 TEM image of the magnetic polystyrene prepared in Example 2;

[0034] Figure 6 TEM image of the magnetic polystyrene prepared in Example 3;

[0035] Figure 7 TEM image of the magnetic polystyrene prepared in Example 4;

[0036] Figure 8 This is the TEM image of the magnetic polystyrene prepared in Comparative Example 1. DETAILED DESCRIPTION

[0037] The present invention will be further described in detail below with reference to specific embodiments. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to provide a more thorough and comprehensive understanding of the present disclosure.

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0039] the term

[0040] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0041] In the present invention, the selection range of "and / or", "or / and", and "and / or" includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, and the said any and all combinations include any combination of two related listed items, any more related listed items, or all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that the technical solution undoubtedly includes technical solutions connected by "logical and" and technical solutions connected by "logical or". For example, "A and / or B" includes three parallel solutions of A, B and A+B. For example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (that is, the technical solution of all being connected by "logical OR"), and also includes any and all combinations of A, B, C, and D, that is, the combination of any two or any three of A, B, C, and D, and also includes the four-item combination of A, B, C, and D (that is, the technical solution of all being connected by "logical AND").

[0042] In the present invention, "plurality", "multiple", "multiple times", "multiple", etc., unless otherwise specified, refer to a number greater than or equal to 2. For example, "one or more" means one or more than or equal to two.

[0043] In the present invention, "combinations thereof", "any combination thereof", "any combination thereof" and the like include all suitable combinations of any two or more of the listed items.

[0044] In the present invention, the “suitable” mentioned in “suitable combination”, “suitable method”, “any suitable method”, etc. shall be based on the ability to implement the technical solution of the present invention, solve the technical problem of the present invention, and achieve the expected technical effect of the present invention.

[0045] In the present invention, “preferred”, “better”, “more preferred” and “suitable” are only used to describe implementation methods or examples with better effects, and it should be understood that they do not constitute a limitation on the scope of protection of the present invention.

[0046] In the present invention, the terms “further”, “further”, “particularly”, etc. are used for descriptive purposes to indicate differences in content, but should not be understood as limiting the scope of protection of the present invention.

[0047] In this disclosure, the terms "optionally," "optional," and "optional" are optional and refer to either option, i.e., to the selection of either option from the two parallel options of "optional" or "optional." If multiple "optional" terms appear in a technical solution, each "optional" term is independent unless otherwise specified and there are no conflicts or constraints.

[0048] In the present invention, in the "first aspect," "second aspect," "third aspect," "fourth aspect," etc., the terms "first," "second," "third," "fourth," etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance or quantity, nor as implicitly indicating the importance or quantity of the technical features indicated. Furthermore, "first," "second," "third," "fourth," etc. serve only as non-exhaustive enumeration and description and should be understood not to constitute a closed-ended limitation on quantity.

[0049] In the present invention, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0050] In the present invention, when referring to a numerical interval (i.e., a numerical range), unless otherwise specified, the optional numerical distribution is considered continuous within the above numerical interval and includes the two numerical endpoints of the numerical range (i.e., the minimum value and the maximum value), as well as each numerical value between the two numerical endpoints. Unless otherwise specified, when a numerical interval refers only to integers within the numerical interval, it includes the two endpoint integers of the numerical range, as well as each integer between the two endpoints. In this article, it is equivalent to directly listing each integer, such as t is an integer selected from 1 to 10, indicating that t is any integer selected from the group of integers consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. In addition, when multiple ranges are provided to describe features or characteristics, these ranges can be merged. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges included therein.

[0051] The temperature parameters in the present invention, unless otherwise specified, may be either constant temperature or fluctuating within a certain temperature range. It should be understood that the constant temperature treatment allows for temperature fluctuations within the precision range of the instrument control. Fluctuations within ranges such as ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are permitted.

[0052] In the present invention, when it comes to percentage content, unless otherwise specified, for solid-liquid mixing and solid-solid mixing, it refers to mass percentage, and for liquid-liquid mixing, it refers to volume percentage.

[0053] In the present invention, when referring to percentage concentration, unless otherwise specified, it refers to the final concentration. The final concentration refers to the percentage of the added component in the system after the addition of the component.

[0054] In the present invention, % (w / w) and wt% both represent weight percentage, % (v / v) refers to volume percentage, and % (w / v) refers to mass volume percentage.

[0055] There are many methods for synthesizing magnetic polystyrene microspheres, such as in situ method, embedding method and monomer polymerization method. Among them, monomer polymerization method mainly includes microemulsion polymerization method, dispersion polymerization method, suspension polymerization method, etc. Monomer polymerization method is currently the most widely used method for preparing magnetic polymers. It mainly refers to a method in which magnetic nanoparticles and polymerization monomers are present in the polymerization system, and appropriate initiators, surfactants and other additives are added to the polymerization system according to actual conditions, and then different polymerization methods are used to prepare magnetic polymers. However, the direct preparation of magnetic polystyrene microspheres by methods such as monomer polymerization still generally has the problem of poor uniformity of the synthesized particle size. In addition, the magnetic nanoparticles are prone to uneven dispersion in the magnetic polystyrene microspheres, resulting in deviations in the magnetic response of the magnetic polystyrene microspheres.

[0056] In order to solve the above problems, the present invention provides a method for preparing magnetic polystyrene microspheres. In one embodiment, the preparation method comprises the following steps:

[0057] Step 1: Preparation of magnetic nanoparticles

[0058] It is understood that the magnetic nanoparticles can be prepared by a co-precipitation method, which comprises the following steps:

[0059] Ferric dichloride, ferric chloride and water are mixed, and an alkaline substance is added to react to prepare the magnetic nanoparticles.

[0060] Optionally, the molar ratio of ferric dichloride to ferric chloride is 1:(1-3).

[0061] Optionally, the alkaline substance is sodium hydroxide or ammonia water.

[0062] In this embodiment, a portion of sodium hydroxide is first added, reacted at 60-80° C. for 25-35 minutes, and then the remaining sodium hydroxide is added until the pH value of the system reaches 10-11, and the reaction is stirred at 600-1000 rpm for 0.5-1.5 hours.

[0063] It is understood that after the reaction is completed, the magnetic nanoparticles can be collected by magnetic separation.

[0064] Step 2: Preparation of modified magnetic nanoparticles

[0065] The magnetic nanoparticles, polyethylene glycol (PEG) and a solvent are mixed and stirred to react so that the polyethylene glycol covers the magnetic nanoparticles to prepare modified magnetic nanoparticles, wherein the polymerization degree of the polyethylene glycol is 400-6000.

[0066] Adding polyethylene glycol to coat and modify the magnetic nanoparticles is beneficial to improving the dispersibility of the magnetic nanoparticles and ensuring that they can be evenly distributed inside the polystyrene seed microspheres after subsequent swelling.

[0067] The inventors have verified through experiments that when the degree of polymerization of polyethylene glycol is 400 to 6000, it has a significant effect on improving the dispersibility of magnetic nanoparticles. Preferably, the degree of polymerization of polyethylene glycol is 1000 to 3000. Within this range, the morphology of the magnetic beads is good and the magnetic nanoparticles are well dispersed within the polystyrene seed microspheres.

[0068] Optionally, the mass ratio of the magnetic nanoparticles to polyethylene glycol is 1:(5-20).

[0069] Optionally, the solvent is ethanol.

[0070] Optionally, the temperature of the stirring reaction is 40-60°C.

[0071] Optionally, the stirring reaction time is 0.5h to 1h.

[0072] Optionally, the stirring speed of the stirring reaction is 600 rpm to 1000 rpm.

[0073] Optionally, the stirring reaction is carried out under a protective atmosphere. Further optionally, the protective atmosphere is nitrogen.

[0074] Step 3: Preparation of polystyrene seed microspheres

[0075] It is understood that polystyrene seed microspheres can be prepared by dispersion polymerization, which comprises the following steps:

[0076] Methacrylic acid (MAA), styrene monomer and dispersant solution are mixed, and an initiator is added to cause a polymerization reaction to prepare polystyrene seed microspheres.

[0077] Optionally, the dispersant is polyvinylpyrrolidone (PVP).

[0078] Optionally, the solvent of the dispersant solution is ethanol.

[0079] Optionally, the initiator is potassium persulfate (KPS) or azobisisobutyl cyanide (AIBN).

[0080] Optionally, the polymerization temperature is 60-80°C.

[0081] Optionally, the stirring speed of the polymerization reaction is 200 rpm to 300 rpm.

[0082] Optionally, the polymerization reaction time is 20 hours to 28 hours.

[0083] The polystyrene seed microspheres prepared by the above method can be prepared into micron-sized seed microspheres with uniform particle size and good dispersibility.

[0084] Step 4: Prepare magnetic beads

[0085] The polystyrene seed microspheres, the modified magnetic nanoparticles, an aqueous solution of sodium dodecyl sulfate (SDS) and a swelling agent are mixed, and the modified magnetic nanoparticles are allowed to enter the polystyrene seed microspheres by utilizing the swelling and shrinkage of the polystyrene seed microspheres to prepare magnetic beads.

[0086] Optionally, the swelling agent includes a good solvent and a poor solvent, and the volume ratio of the good solvent to the poor solvent is 1:(1-20). The use of a combination of a good solvent and a poor solvent can ensure the swelling effect while reducing the adverse effects of the swelling agent on the microsphere morphology of the magnetic sphere.

[0087] Optionally, the good solvent is selected from one or more of dichloromethane, chloroform, petroleum ether and chlorododecane.

[0088] Optionally, the poor solvent is selected from one or more of methanol, ethanol and isopropanol.

[0089] This embodiment adopts a swelling method. Based on the polystyrene seed microspheres with uniform particle size and good dispersibility obtained in step 3, the modified magnetic nanoparticles are introduced into the polystyrene seed microspheres by utilizing the swelling and contraction of the polystyrene seed microspheres under the action of a swelling agent and an SDS aqueous solution.

[0090] Step 5: Coating the surface of the magnetic beads with a shell layer.

[0091] Optionally, the shell layer is a polystyrene layer. By coating the shell layer, the risk of leakage of the modified magnetic nanoparticles can be reduced.

[0092] Optionally, coating the surface of the magnetic beads with a polystyrene layer comprises the following steps:

[0093] Magnetic beads, styrene monomer and a cross-linking agent are mixed, an initiator is added, a polymerization reaction occurs, and a polystyrene layer is coated on the surface of the magnetic beads.

[0094] Optionally, the cross-linking agent is divinylbenzene (DVB).

[0095] Optionally, the initiator is potassium persulfate (KPS) or azobisisobutyl cyanide (AIBN).

[0096] Optionally, the polymerization temperature is 60-80°C.

[0097] Optionally, the polymerization reaction time is 1 h to 3 h.

[0098] Optionally, before the polymerization reaction, a step of adding a carboxyl compound is included. By adding the carboxyl compound to achieve carboxyl modification of the shell, it is beneficial to improve the dispersibility of the magnetic polystyrene microspheres and the feasibility of coupling with proteins.

[0099] Optionally, the carboxyl compound is undecylenic acid or oleic acid.

[0100] In this embodiment, magnetic nanoparticles are first coated with polyethylene glycol of a specific degree of polymerization, and then the polyethylene glycol-coated magnetic nanoparticles are introduced into polystyrene seed microspheres through a swelling method. The polyethylene glycol coating improves the dispersibility of the magnetic nanoparticles, ensuring that they are evenly distributed within the polystyrene seed microspheres after subsequent swelling. The coating shell prevents leakage of the magnetic nanoparticles. The magnetic polystyrene microspheres obtained by this method have good particle size uniformity and even dispersion of the magnetic nanoparticles within them, making them suitable for the synthesis of fluorescently encoded microspheres.

[0101] The present invention also provides magnetic polystyrene microspheres, which, in one embodiment, are prepared by the above-mentioned preparation method.

[0102] The advantages of the magnetic polystyrene microspheres of this embodiment are as described above and will not be elaborated on again.

[0103] The following is further described in conjunction with specific examples and comparative examples. Unless otherwise specified, the raw materials involved in the following specific examples and comparative examples can be sourced from commercial sources. The instruments used can be sourced from commercial sources unless otherwise specified. The processes involved can be selected conventionally by those skilled in the art unless otherwise specified.

[0104] Among them, PEG2000 is polyethylene glycol with a degree of polymerization of 2000; PVP is polyvinyl pyrrolidone; MAA is methacrylic acid; DCM is dichloromethane; SDS is sodium dodecyl sulfate; DVB is divinylbenzene; and KPS is potassium persulfate.

[0105] Example 1

[0106] This embodiment provides a magnetic polystyrene microsphere and a preparation method thereof, the steps are as follows:

[0107] Step 1: Preparation of magnetic nanoparticles

[0108] Weigh appropriate amounts of FeCl₃·6H₂O and FeCl₂·4H₂O and add water to prepare 0.1M FeCl₂ and 0.1M FeCl₃ solutions, respectively. Mix 10mL of 0.1M FeCl₂ solution and 20mL of 0.1M FeCl₃ solution and filter through a 0.22μm aqueous filter to obtain mixed solution A.

[0109] Under vigorous stirring, NaOH aqueous solution (5 mL, 0.4 M) was added dropwise to the mixed solution A, and the mixture was reacted in an oil bath at 70° C. for 30 min. NaOH aqueous solution (0.4 M) was continued to be added dropwise, the pH value was adjusted to 10-11, and the mixture was stirred at 800 rpm for 1 h to obtain a reaction solution containing magnetic nanoparticles, wherein the magnetic nanoparticles were Fe3O4 nanoparticles. The magnetic nanoparticles were magnetically separated and washed with anhydrous ethanol and ultrapure water, and finally preserved with anhydrous ethanol to obtain an anhydrous ethanol solution of magnetic nanoparticles.

[0110] Step 2: Preparation of modified magnetic nanoparticles

[0111] Take 2 mL (about 50 mg / mL) of the anhydrous ethanol solution of the magnetic nanoparticles obtained in step 1 and add it to a 50 mL eggplant-shaped flask, add 5 mL of PEG2000 aqueous solution (0.2 g / mL) and 10 mL of anhydrous ethanol, pass nitrogen, and stir at 800 rpm in a 50°C oil bath for 1 h to obtain modified magnetic nanoparticles (PEG-Fe3O4NPS).

[0112] Step 3: Preparation of polystyrene seed microspheres

[0113] See also Figure 1 Weigh 0.4 g of PVP-K30, transfer it to a 250 mL flask, add 50 mL of anhydrous ethanol, oscillate and ultrasonically dissolve it, then add a mechanical stirring paddle and transfer it to an oil bath to obtain a PVP solution.

[0114] In a 50 mL centrifuge tube, add 120 μL of MAA and 15 mL of styrene monomer, shake and ultrasonically mix, then add dropwise into the PVP solution using a separatory funnel, stir at 250 rpm for 10 min, and then pass nitrogen for 10 min to obtain mixed solution B.

[0115] Weigh 0.12 g of KPS, add 1 mL of deionized water, dissolve it by ultrasonication, and then add it dropwise to mixed solution B using a pipette. Then, heat it to 70°C and stir it at 250 rpm for 24 h. After the reaction, transfer the solution in the flask to a 50 mL centrifuge tube, centrifuge it at 4000 rpm, wash it twice with anhydrous ethanol, wash it once with ultrapure water, and finally store it in ultrapure water to obtain an aqueous solution of polystyrene seed microspheres.

[0116] Step 4: Prepare magnetic beads

[0117] Continue to see Figure 1 , weigh 30 mL of 0.25 wt% SDS aqueous solution into a 250 mL flask, add 200 μL of the aqueous solution of the polystyrene seed microspheres in step 3 to the above flask, ultrasonically disperse, then add 200 uL of the modified magnetic nanoparticles (PEG-Fe3O4NPS) in step 2, ultrasonically disperse and mix, then add 100 uL of a mixed solution of dichloromethane and methanol (volume ratio = 1:4), heat in an oil bath at 50°C, stir at 200 rpm for 3 hours, utilize the swelling and contraction of the polystyrene seed microspheres to make the modified magnetic nanoparticles enter the polystyrene seed microspheres, synthesize magnetic beads, and obtain a reaction solution containing magnetic beads.

[0118] Step 5: Coating the surface of the magnetic beads with a shell layer.

[0119] To the reaction solution containing magnetic beads in step 4, 100 μL of styrene monomer, 10 μL of DVB, and 10 μL of undecylenic acid were added, and nitrogen was passed through for 10 minutes to obtain a mixed solution C.

[0120] 12.5 mg of KPS was added to the mixed solution C, the temperature was raised to 70°C, stirring was continued for 2 h, the mixture was quickly cooled to room temperature, and the mixture was transferred to a 50 mL centrifuge tube for magnetic separation and washing to obtain magnetic polystyrene. The obtained magnetic polystyrene was washed twice with anhydrous ethanol and finally stored in anhydrous ethanol to obtain an anhydrous ethanol solution containing magnetic polystyrene microspheres.

[0121] The above solution was taken and dried, and the obtained powder was characterized by TEM. The TEM image of the magnetic polystyrene of Example 1 is shown in Figure 2 and Figure 3 ,from Figure 2 and Figure 3 It can be seen that the magnetic polystyrene is spherical, with a smooth surface, complete shape, and uniform brightness, indicating that the PEG-Fe3O4NPS is evenly dispersed in the magnetic polystyrene microspheres. The obtained powder is placed under a microscope for observation. The microscope photo of the magnetic polystyrene in Example 1 is shown in FIG. Figure 3 ,from Figure 3 It can be seen that the magnetic polystyrene has uniform particle size and good dispersion.

[0122] Example 2

[0123] This embodiment provides a magnetic polystyrene microsphere and a preparation method thereof, which is basically the same as that of Example 1, with the main difference being that PEG2000 is replaced by PEG600.

[0124] The TEM image of the magnetic polystyrene microspheres obtained in this example is shown in FIG. Figure 5 .

[0125] Example 3

[0126] This embodiment provides a magnetic polystyrene microsphere and a preparation method thereof, which is basically the same as that of Example 1, with the main difference being that PEG2000 is replaced by PEG4000.

[0127] The TEM image of the magnetic polystyrene microspheres obtained in this example is shown in FIG. Figure 6 .

[0128] contrast Figure 4-Figure 6 This indicates that the degree of polymerization of PEG affects the dispersibility of PEG-Fe3O4NPS in polystyrene seed microspheres and the morphology of magnetic polystyrene.

[0129] Example 4

[0130] This embodiment provides a magnetic polystyrene microsphere and a preparation method thereof, which is basically the same as that of Example 1, except that 100 μL of a mixed solution of dichloromethane and methanol (volume ratio = 1:4) is replaced with 100 μL of a mixed solution of petroleum ether and methanol (volume ratio = 1:4). The steps are as follows:

[0131] The TEM image of the magnetic polystyrene microspheres obtained in this example is shown in FIG. Figure 7 .contrast Figure 1 and Figure 7 It can be seen that the swelling agent has an impact on whether PEG-Fe3O4NPS can completely enter the interior of the polystyrene seed microspheres.

[0132] Comparative Example 1

[0133] This comparative example provides a magnetic polystyrene microsphere and a preparation method thereof, which is basically the same as Example 1, except that PEG2000 is replaced with oleic acid. The steps are as follows:

[0134] The TEM image of the magnetic polystyrene microspheres obtained in this comparative example is shown in FIG. Figure 8 .contrast Figure 1 and Figure 8It can be seen that compared with using oleic acid to coat magnetic nanoparticles, using PEG at a specific degree of polymerization to coat magnetic nanoparticles is beneficial for the magnetic nanoparticles to enter the interior of the polystyrene seed microspheres through swelling, and can ensure that the magnetic nanoparticles after swelling into the polystyrene seed microspheres can be evenly distributed inside them and are not easy to agglomerate.

[0135] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0136] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A method for preparing magnetic polystyrene microspheres, characterized in that: The following steps are involved: Providing magnetic nanoparticles, mixing the magnetic nanoparticles, polyethylene glycol, and a solvent, stirring and reacting to allow the polyethylene glycol to coat the magnetic nanoparticles, thereby preparing modified magnetic nanoparticles, wherein the degree of polymerization of the polyethylene glycol is 1000-3000; Providing polystyrene seed microspheres, mixing the polystyrene seed microspheres, the modified magnetic nanoparticles, an aqueous solution of sodium lauryl sulfate, and a swelling agent, and utilizing the swelling and shrinkage of the polystyrene seed microspheres to allow the modified magnetic nanoparticles to enter the polystyrene seed microspheres to prepare magnetic beads; A shell layer is coated on the surface of the magnetic beads; The mass ratio of the magnetic nanoparticles to polyethylene glycol is 1:(5-20); The reaction conditions for coating the magnetic nanoparticles with polyethylene glycol include: a) the stirring reaction temperature is 40-60° C.; b) the stirring reaction time is 0.5 h-1 h; c) the stirring reaction speed is 600 rpm-1000 rpm; and d) the stirring reaction is performed under a protective atmosphere.

2. The method for preparing magnetic polystyrene microspheres according to claim 1, wherein: The solvent is ethanol.

3. The method for preparing magnetic polystyrene microspheres according to any one of claims 1 to 2, wherein: The swelling agent includes a good solvent and a poor solvent, and the volume ratio of the good solvent to the poor solvent is 1:(1-20).

4. The method for preparing magnetic polystyrene microspheres according to claim 3, wherein: The good solvent is selected from one or more of dichloromethane, chloroform, petroleum ether and chlorododecane.

5. The method for preparing magnetic polystyrene microspheres according to claim 3, characterized in that: The poor solvent is selected from one or more of methanol, ethanol and isopropanol.

6. The method for preparing magnetic polystyrene microspheres according to any one of claims 1 to 2 and 5, characterized in that: The shell layer is a polystyrene layer.

7. The method for preparing magnetic polystyrene microspheres according to claim 6, characterized in that: Coating the polystyrene layer on the surface of the magnetic beads comprises the following steps: Mixing magnetic beads, styrene monomer and cross-linking agent, adding initiator, causing polymerization reaction, and coating the surface of the magnetic beads with a polystyrene layer; Optionally, before the polymerization reaction occurs, a step of adding a carboxyl compound is also included.

8. The method for preparing magnetic polystyrene microspheres according to any one of claims 1 to 2, 5 and 7, characterized in that: The preparation method of the polystyrene seed microspheres comprises the following steps: Methacrylic acid, styrene monomer and dispersant solution are mixed, an initiator is added, a polymerization reaction occurs, and polystyrene seed microspheres are prepared.

9. The method for preparing magnetic polystyrene microspheres according to any one of claims 1 to 2, 5 and 7, wherein: The preparation method of the magnetic nanoparticles comprises the following steps: Ferric dichloride, ferric chloride and water are mixed, and an alkaline substance is added to react to prepare the magnetic nanoparticles.

10. A magnetic polystyrene microsphere, characterized in that: Prepared by the preparation method according to any one of claims 1 to 9.

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