A method for synthesizing hollow silica magnetic microspheres

Abstract

The present invention relates to the field of biomedicine technology, and in particular to a method for synthesizing hollow silica magnetic microspheres. Hydrophobic ferrite magnetic nanoparticles are swollen into non-crosslinked polystyrene microspheres, and a portion of the hydrophobic ferrite magnetic nanoparticles are embedded on the surface of the non-crosslinked polystyrene microspheres to obtain magnetic microspheres. Surfactant molecules with positive electrophilic ends are adsorbed on the surface of the microspheres through hydrophobic action. Subsequently, the microspheres are dispersed in a solution of ethyl orthosilicate and hydrolyzed on the surface of the magnetic microspheres to form a silica surface to obtain silica magnetic microspheres. The non-crosslinked polystyrene core is dissolved, and the linear molecules are washed off with ethanol. After washing, the hollow silica magnetic microspheres are dissolved in water to obtain hollow silica magnetic microspheres. Compared with the prior art, the method for synthesizing hollow silica magnetic microspheres of the present invention ensures the uniformity of the hollow microspheres, improves the magnetism, has more choices for the polystyrene particle size, does not need to be coated with a thick shell layer, and avoids the weakening of the magnetism caused by the reduction of the specific gravity of the magnetic particles.

Description

[Technical field]

[0001] The invention relates to the technical field of biomedicine, and in particular to a method for synthesizing hollow silica magnetic microspheres. [Background technology]

[0002] Magnetic microspheres have the characteristics of superparamagnetism and can be used for magnetic separation, which is conducive to automated operation. Therefore, they have always been a research hotspot in the field of materials and are also widely used in the biomedical field. Silica magnetic beads are one of the hottest ones. However, due to the high density and rapid sedimentation of silica magnetic beads, their application range in the biomedical field is limited. Therefore, how to reduce the density has become the key to breaking through its own limitations.

[0003] Hollow silica microspheres have the characteristics of low density. Common methods for preparing hollow silica microspheres include polymer template method, vesicle template method, layer-by-layer self-assembly method, etc. The silica magnetic beads and microspheres synthesized by the prior art have high density and are easy to settle. The particle size distribution of hollow magnetic silica microspheres is not uniform, the magnetism is weak, and the particle size coverage range is narrow, generally below 100nm, which is not conducive to application in the fields of biomedicine and so on. [Summary of the invention]

[0004] In order to overcome the above problems, the present invention provides a method for synthesizing hollow silica magnetic microspheres which can effectively solve the above problems.

[0005] The present invention provides a technical solution to solve the above technical problem: a method for synthesizing hollow silica magnetic microspheres is provided, comprising the following steps:

[0006] Step S1, taking 1g of non-crosslinked polystyrene microspheres and dispersing them in 100ml of isobutanol, then taking 100mg of hydrophobic ferrite magnetic nanoparticles with oleic acid bound to the surface and dissolving them in 25ml of dichloromethane and 75ml of isobutanol, mixing the two solutions in a ratio of 1:1, shaking for 2 hours after swelling, swelling the hydrophobic ferrite magnetic nanoparticles into the non-crosslinked polystyrene microspheres, and at the same time, a part of the hydrophobic ferrite magnetic nanoparticles are embedded on the surface of the non-crosslinked polystyrene microspheres, to obtain magnetic microspheres;

[0007] Step S2, preparing 100 ml of a 1% surfactant solution with a positive hydrophilic end, utilizing the property of the surfactant with a positive hydrophilic end being lipophilic at one end and hydrophilic at the other end, dispersing magnetic microspheres in the solution, and allowing the hydrophobic region of the surfactant to adsorb on the surface of the magnetic microspheres through hydrophobic interaction, and throwing out the hydrophilic end;

[0008] Step S3, removing the aqueous solution from the magnetic microspheres by magnetic separation, washing them twice with ethanol, and then dissolving them in 1 L of ethanol;

[0009] Step S4, after dispersion, add 20 ml of tetraethyl orthosilicate, mix thoroughly, add 10 ml of alkaline solution, after encountering the alkaline solution, tetraethyl orthosilicate is hydrolyzed on the surface of the magnetic microspheres to form a silica surface, mix again evenly, shake for 4 hours, remove ethanol, unreacted tetraethyl orthosilicate and alkaline solution by magnetic separation, wash three times with water, and then obtain silica magnetic microspheres;

[0010] Step S5, drying the obtained silica magnetic microspheres, adding them to 50 ml of dichloromethane to dissolve the non-crosslinked polystyrene core, washing the linear molecules with ethanol, washing three times, and dissolving them in water to obtain hollow silica magnetic microspheres.

[0011] Preferably, in step S1, the particle size of the non-crosslinked polystyrene microspheres is 0.1 μm to 50 μm.

[0012] Preferably, in step S1, the particle size of the hydrophobic ferrite magnetic nanoparticles is 5 nm to 50 nm.

[0013] Preferably, in step S2, the surfactant is an amphiphilic molecule having a nitrogen atom at the hydrophilic end and exhibiting positive electrophilicity.

[0014] Preferably, in step S4, the alkaline solution may be aqueous ammonia or aqueous sodium hydroxide solution.

[0015] Compared with the prior art, the synthesis method of hollow silica magnetic microspheres of the present invention has the following advantages:

[0016] Beneficial effects:

[0017] 1. Using polystyrene microspheres as templates ensures the uniformity of hollow microspheres;

[0018] 2. Polystyrene particle size can be selected in more ways, and it does not need to be coated with a very thick shell layer, which can avoid the weakening of magnetism caused by the decrease in the specific gravity of magnetic particles, and has a wide range of application prospects and use value;

[0019] 3. Non-cross-linked polystyrene microspheres can swell into more hydrophobic magnetic particles, while improving the magnetic properties, and after forming a silica shell, it can be dissolved by organic solvents, leaving only the hollow magnetic silica microsphere structure;

[0020] 4. The surfactant molecules with positive hydrophilic end are distributed on the surface of the microspheres and adsorb ethyl orthosilicate. The shell formed is defect-free and very complete.

Brief Description of the Drawings

[0021] Figure 1 The flowchart of the synthesis method of hollow silica magnetic microspheres of the present invention;

[0022] Figure 2The scanning electron microscope image is of 6-micron hollow silica magnetic microspheres prepared by the synthesis method of hollow silica magnetic microspheres of the present invention. [Specific implementation method]

[0023] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and implementation examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0024] It should be noted that in the embodiments of the present invention, all directional indications (such as up, down, left, right, front, back, etc.) are limited to relative positions on the specified view, rather than absolute positions.

[0025] In addition, in the present invention, descriptions such as "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0026] See also Figure 1 and Figure 2 The method for synthesizing hollow silica magnetic microspheres of the present invention comprises the following steps:

[0027] Step S1, take 1g of non-crosslinked polystyrene microspheres and disperse them in 100ml of isobutanol, then take 100mg of hydrophobic ferrite magnetic nanoparticles with oleic acid bound to the surface and dissolve them in 25ml of dichloromethane and 75ml of isobutanol, mix the two solutions in a ratio of 1:1, shake them for 2 hours after swelling, and swell the hydrophobic ferrite magnetic nanoparticles into the non-crosslinked polystyrene microspheres, and at the same time, a part of the hydrophobic ferrite magnetic nanoparticles is embedded on the surface of the non-crosslinked polystyrene microspheres to obtain magnetic microspheres. At this time, the magnetic microspheres are in a hydrophobic state.

[0028] In the step S1, the particle size of the non-crosslinked polystyrene microspheres is 0.1 μm to 50 μm.

[0029] In the step S1, the particle size of the hydrophobic ferrite magnetic nanoparticles is 5 nm to 50 nm.

[0030] Step S2, prepare 100 ml of a 1% surfactant solution with a positive hydrophilic end, and utilize the property that the surfactant with a positive hydrophilic end is lipophilic at one end and hydrophilic at the other end to disperse the magnetic microspheres in the solution. The hydrophobic region of the surfactant is adsorbed on the surface of the magnetic microspheres through hydrophobic interaction, and the hydrophilic end is thrown out.

[0031] In step S2, the hydrophilic end of the surfactant molecule has the characteristic of being electropositive, including but not limited to PVP with a molecular weight of 5000 to 1000000, alkyl ammonium bromide molecules with a carbon chain length of 8 to 24, etc., which contain nitrogen atoms at the hydrophilic end and are electropositive. That is, the surfactant is an amphiphilic molecule with a nitrogen atom at the hydrophilic end and is electropositive.

[0032] In step S2, 100 ml of a 1% PVP (K30) solution is prepared, and the properties of the PVP surfactant are used to disperse the magnetic microspheres in the PVP solution. The hydrophobic region of the PVP is adsorbed on the surface of the magnetic microspheres through hydrophobic interactions, and the hydrophilic end is thrown out. Since the hydrophilic end of the PVP molecule contains nitrogen atoms, it is slightly electropositive. PVP is polyvinyl pyrrolidone, and K30 refers to the molecular weight. PVP is usually abbreviated in this way, and the latter represents the molecular weight range, and K30 represents the molecular weight within a certain range.

[0033] Step S3, the magnetic microspheres are subjected to magnetic separation to remove the aqueous solution, washed twice with ethanol, and then dissolved in 1 L of ethanol.

[0034] Step S4, after dispersion, add 20ml of tetraethyl orthosilicate solution, after fully mixing, add 10ml of alkaline solution, after encountering alkaline solution, tetraethyl orthosilicate is hydrolyzed on the surface of magnetic microspheres to form a silicon dioxide surface, mix evenly again, shake for 4 hours, remove ethanol, unreacted tetraethyl orthosilicate and alkaline solution by magnetic separation, wash three times with water, and obtain silicon dioxide-coated magnetic microspheres, i.e. silicon dioxide magnetic microspheres. Wherein, the tetraethyl orthosilicate solution can be a tetraethyl orthosilicate aqueous solution, a tetraethyl orthosilicate alcohol solution, or a mixed solution of the two.

[0035] In the step S4, since tetraethyl orthosilicate is electronegative, tetraethyl orthosilicate will be adsorbed on the surface of the magnetic microspheres.

[0036] In step S4, the alkaline solution may be aqueous ammonia or aqueous sodium hydroxide solution.

[0037] Step S5, drying the obtained silica magnetic microspheres, adding them to 50 ml of dichloromethane to dissolve the non-crosslinked polystyrene core, washing the linear molecules with ethanol, washing three times, and dissolving them in water to obtain hollow silica magnetic microspheres.

[0038] In the above steps, the dichloromethane can be trichloromethane, 1,2-dichloromethane, etc.

[0039] from Figure 2 It can be seen that the 6-micron hollow silica magnetic microspheres prepared by the synthesis method of hollow silica magnetic microspheres of the present invention are uniform and have a complete surface structure.

[0040] The first embodiment of the synthesis method of hollow silica magnetic microspheres of the present invention is as follows: 1g of non-crosslinked 0.2μm polystyrene microspheres is dispersed in 100ml of isobutanol, and then 100mg of 6nm hydrophobic ferrite magnetic nanoparticles with oleic acid on the surface are dissolved in 25ml of dichloromethane and 75ml of isobutanol, and the two solutions are mixed in a ratio of 1:1, and the swelling is followed by shaking for 2 hours, so that the hydrophobic magnetic ferrite nanoparticles are swollen into the interior of the microspheres, and a part of the hydrophobic magnetic ferrite nanoparticles are embedded on the surface of the microspheres to obtain magnetic microspheres. At this time, the microspheres are in a hydrophobic state. 100ml of a 1% PVP solution is prepared, and the magnetic microspheres are dispersed in this solution by utilizing the properties of the PVP surfactant. The hydrophobic region of the PVP is adsorbed on the surface of the microspheres through hydrophobic interactions, and the hydrophilic end is thrown out. Since the hydrophilic end of the PVP molecule contains nitrogen atoms, it is slightly electropositive. The magnetic microspheres are separated by magnetic separation, the aqueous solution is removed, and the magnetic microspheres are washed twice with ethanol, and finally dissolved in 1L of ethanol. After dispersion, 20ml of ethyl orthosilicate is added. Since tetraethyl orthosilicate is electronegative, it will adsorb on the surface of magnetic microspheres. After fully mixing, add 10ml of ammonia water. After meeting ammonia water, tetraethyl orthosilicate is hydrolyzed on the surface of the microspheres to form a silica surface. Mix evenly again, shake for 4 hours, remove ethanol, tetraethyl orthosilicate, and ammonia water by magnetic separation, and wash three times with water to obtain silica-coated magnetic microspheres. After drying the obtained silica magnetic microspheres, add them to 50ml of dichloromethane, dissolve the non-crosslinked polystyrene core, wash the linear molecules with ethanol, wash three times, and dissolve in water to obtain hollow silica magnetic beads.

[0041] The second embodiment of the synthesis method of hollow silica magnetic microspheres of the present invention is as follows: 1g of non-crosslinked 15μm polystyrene microspheres is dispersed in 100ml of isobutanol, and then 100mg of 18nm hydrophobic ferrite magnetic nanoparticles with oleic acid on the surface are dissolved in 25ml of dichloromethane and 75ml of isobutanol, and the two solutions are mixed in a ratio of 1:1, and the swelling is followed by shaking for 2 hours, so that the hydrophobic magnetic ferrite nanoparticles are swollen into the interior of the microspheres, and a part of the hydrophobic magnetic ferrite nanoparticles are embedded in the surface of the microspheres to obtain magnetic microspheres. At this time, the microspheres are in a hydrophobic state. 100ml of a 1% PVP solution is prepared, and the magnetic microspheres are dispersed in this solution by utilizing the properties of the PVP surfactant. The hydrophobic region of the PVP is adsorbed on the surface of the microspheres through hydrophobic interactions, and the hydrophilic end is thrown out. Since the hydrophilic end of the PVP molecule contains nitrogen atoms, it is slightly electropositive. The magnetic microspheres are separated by magnetic separation, the aqueous solution is removed, and the magnetic microspheres are washed twice with ethanol, and finally dissolved in 1L of ethanol. After dispersion, 20ml of ethyl orthosilicate is added. Since tetraethyl orthosilicate is electronegative, it will adsorb on the surface of magnetic microspheres. After fully mixing, add 10ml of ammonia water. After meeting ammonia water, tetraethyl orthosilicate is hydrolyzed on the surface of the microspheres to form a silica surface. Mix evenly again, shake for 4 hours, remove ethanol, tetraethyl orthosilicate, and ammonia water by magnetic separation, and wash three times with water to obtain silica-coated magnetic microspheres. After drying the obtained silica magnetic microspheres, add them to 50ml of dichloromethane, dissolve the non-crosslinked polystyrene core, wash the linear molecules with ethanol, wash three times, and dissolve in water to obtain hollow silica magnetic beads.

[0042] Compared with the prior art, the synthesis method of hollow silica magnetic microspheres of the present invention has the following advantages:

[0043] Beneficial effects:

[0044] 1. Using polystyrene microspheres as templates ensures the uniformity of hollow microspheres;

[0045] 2. Polystyrene particle size can be selected in more ways, and it does not need to be coated with a very thick shell layer, which can avoid the weakening of magnetism caused by the decrease in the specific gravity of magnetic particles, and has a wide range of application prospects and use value;

[0046] 3. Non-cross-linked polystyrene microspheres can swell into more hydrophobic magnetic particles, while improving the magnetic properties, and after forming a silica shell, it can be dissolved by organic solvents, leaving only the hollow magnetic silica microsphere structure;

[0047] 4. The surfactant molecules with positive hydrophilic end are distributed on the surface of the microspheres and adsorb ethyl orthosilicate. The shell formed is defect-free and very complete.

[0048] The above description is only a preferred embodiment of the present invention, and does not limit the patent scope of the present invention. Any modifications, equivalent substitutions and improvements made within the concept of the present invention should be included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing hollow silica magnetic microspheres, characterized in that: The steps include: Step S1, taking 1g of non-crosslinked polystyrene microspheres and dispersing them in 100ml of isobutanol, then taking 100mg of hydrophobic ferrite magnetic nanoparticles with oleic acid bound to the surface and dissolving them in 25ml of dichloromethane and 75ml of isobutanol, mixing the two solutions in a ratio of 1:1, shaking for 2 hours after swelling, swelling the hydrophobic ferrite magnetic nanoparticles into the non-crosslinked polystyrene microspheres, and at the same time, a part of the hydrophobic ferrite magnetic nanoparticles are embedded on the surface of the non-crosslinked polystyrene microspheres, to obtain magnetic microspheres; Step S2, preparing 100 ml of a 1% surfactant solution with a positive hydrophilic end, utilizing the property of the surfactant with a positive hydrophilic end being lipophilic at one end and hydrophilic at the other end, dispersing magnetic microspheres in the solution, and allowing the hydrophobic region of the surfactant to adsorb on the surface of the magnetic microspheres through hydrophobic interaction, and throwing out the hydrophilic end; Step S3, removing the aqueous solution from the magnetic microspheres by magnetic separation, washing them twice with ethanol, and then dissolving them in 1 L of ethanol; Step S4, after dispersion, add 20 ml of tetraethyl orthosilicate, mix thoroughly, add 10 ml of alkaline solution, after encountering the alkaline solution, tetraethyl orthosilicate is hydrolyzed on the surface of the magnetic microspheres to form a silica surface, mix again evenly, shake for 4 hours, remove ethanol, unreacted tetraethyl orthosilicate and alkaline solution by magnetic separation, wash three times with water, and then obtain silica magnetic microspheres; Step S5, drying the obtained silica magnetic microspheres, adding them to 50 ml of dichloromethane to dissolve the non-crosslinked polystyrene core, washing the linear molecules with ethanol, washing three times, and dissolving them in water to obtain hollow silica magnetic microspheres.

2. The method for synthesizing hollow silica magnetic microspheres according to claim 1, wherein: In the step S1, the particle size of the non-crosslinked polystyrene microspheres is 0.1 μm to 50 μm.

3. The method for synthesizing hollow silica magnetic microspheres according to claim 1, characterized in that: In the step S1, the particle size of the hydrophobic ferrite magnetic nanoparticles is 5 nm to 50 nm.

4. The method for synthesizing hollow silica magnetic microspheres according to claim 1, characterized in that: In the step S2, the surfactant is an amphiphilic molecule having a nitrogen atom at the hydrophilic end and showing positive electrophilicity.

5. The method for synthesizing hollow silica magnetic microspheres according to claim 1, characterized in that: In step S4, the alkaline solution may be aqueous ammonia or aqueous sodium hydroxide solution.

Images