CN113066657B - A kind of hedgehog-shaped magnetic microsphere and preparation method thereof - Google Patents

Abstract

The invention discloses a preparation method of hedgehog-shaped magnetic microspheres, which is based on magnetic nano particles wrapped by silicon dioxide, takes a silicon dioxide layer as a template, enables the silicon dioxide layer to be completely etched to generate a hedgehog-shaped shell structure by a one-step hydrothermal method, cleans the hedgehog-shaped shell structure by deionized water after reaction, and collects magnets to obtain the hedgehog-shaped magnetic microspheres. The microsphere is characterized by comprising an inner core and a magnesium silicate shell, wherein the magnesium silicate shell is in a nano needle-like structure, is similar to a hedgehog in shape and has a strong surface function; the kernel is magnetic ferroferric oxide nano particles, and the micro-spheres are endowed with rapid magnetic responsiveness, so that the controllable motion of the hedgehog-shaped magnetic micro-spheres can be realized under the action of an external magnetic field. The hedgehog-shaped magnetic microsphere preparation method based on the magnetic nanoparticles has the advantages of low cost, easiness in operation, convenience, reliability and the like.

Description

A kind of hedgehog-shaped magnetic microsphere and preparation method thereof

technical field

The invention relates to the field of biological materials, in particular to a hedgehog-shaped magnetic microsphere and a preparation method thereof.

Background technique

Magnetic nanomaterials have attracted extensive attention due to their superparamagnetic properties, good dispersibility and biocompatibility, and have excellent application prospects in the field of biotechnology, including magnetic targeted drug delivery, medical imaging, cancer diagnosis, sewage treatment, cell separation etc. Among them, the unique magnetic response performance of magnetic microspheres makes magnetic separation technology a core technology in the field of separation analysis. Magnetic beads will not undergo magnetic aggregation without an external magnetic field. When an external magnetic field occurs, these magnetic beads can respond quickly to achieve separation. target enrichment. Magnetic microspheres for the enrichment and separation of biomolecules have the advantages of simple operation, rapid enrichment and separation, recyclability, and no introduction of new substances in the separation process.

Common preparation methods of magnetic nanomaterials include microemulsion method, embedding method, solvothermal method, co-precipitation method, etc., but these preparation processes are relatively complicated and have high technical requirements. In addition, the surface structure of traditionally prepared magnetic beads is often relatively simple. Although complex surface group modifications can be carried out, they still have great limitations in the enrichment of biomolecules, which can no longer meet people's application needs. Therefore, magnetic microspheres with larger surface functions, easy preparation, and selective and efficient separation of biomolecules are of great significance in the field of biomedicine.

The hedgehog-shaped magnetic microspheres prepared based on silica-encapsulated magnetic nanoparticles have larger specific surface area, adjustable size, and contain magnetic beads. When a magnetic field is applied, the controllable movement of the hedgehog-shaped magnetic microspheres can be realized, which is flexible, time-saving and convenient.

SUMMARY OF THE INVENTION

In order to solve the shortcomings of simple surface structure and complicated preparation of traditional magnetic microspheres, the present invention provides a hedgehog-shaped magnetic microsphere and a preparation method thereof.

For achieving the above object, the technical scheme provided by the present invention is:

A preparation method of hedgehog-shaped magnetic microspheres, comprising the following steps:

(1) Preparation of magnetic nanoparticles:

In the ethylene glycol solution, add anhydrous ferric chloride, sodium acetate, poly(4-styrenesulfonic acid-co-maleic acid) sodium salt, L-ascorbic acid and an appropriate amount of water in sequence, and stir to form a mixed solution; Add sodium hydroxide to the mixed solution, continue stirring to obtain a brown transparent solution; transfer it to the reaction kettle, and obtain magnetic nanoparticles by one-step hydrothermal method;

(2) Preparation of silica-wrapped magnetic nanoparticles:

Disperse the above magnetic nanoparticles in ethanol, add ammonia water, ultrasonically disperse, slowly add tetraethyl orthosilicate dropwise in a water bath at 50°C, and stir for 1 h to collect the silica-coated magnetic nanoparticles;

(3) Preparation of hedgehog-shaped magnetic microspheres:

A mixed solution of magnesium chloride and ammonium chloride is prepared, mixed evenly with the above-mentioned silica-coated magnetic nanoparticles, ammonia water is added, and ultrasonically dispersed; it is transferred to a reaction kettle, and hedgehog-shaped magnetic microspheres are obtained by a one-step hydrothermal method.

Further, the volume ratio of the ethylene glycol solution described in step (1) to an appropriate amount of water is 160:1 to 800:1.

Further, the size of the magnetic nanoparticles prepared in step (1) can be changed by adjusting the amount of water added: reducing or increasing the amount of water added, the magnetic nanoparticles will shrink or increase accordingly.

Further, the hedgehog-shaped magnetic microspheres described in step (3) can change the size of the microspheres by adjusting the amount of tetraethyl orthosilicate added in step (2): reducing or increasing tetraethyl orthosilicate, The hedgehog-shaped magnetic microspheres shrink or grow accordingly.

Further, the condition of the hydrothermal method in step (1) is to react at 190° C. for 9 hours.

Further, the condition of the hydrothermal method in step (3) is to react at 140° C. for 14 hours.

The hedgehog-shaped magnetic microspheres prepared by the above method have the outer shell of magnesium silicate, a nano-needle structure and a hedgehog-like shape, and the inner core of magnetic ferric oxide nanoparticles, which have good magnetic responsiveness.

The inner core magnetic ferric oxide nanoparticles have a particle size of 60-90 nm, and the magnetic microspheres have a particle size of 250-300 nm.

Compared with the prior art, the beneficial effects of the present invention are:

(1) The present invention prepares hedgehog-shaped magnetic microspheres based on silica-wrapped magnetic nanoparticles, which has low cost, high repeatability, does not require high technical requirements, and is easy to control the size of the hedgehog-shaped magnetic microspheres.

(2) The present invention designs a hedgehog-shaped magnetic microsphere, which has high specific surface area and strong adhesion, can achieve efficient selective enrichment of biomolecules, and is highly practical.

(3) The hedgehog-shaped magnetic microspheres prepared by the present invention can move in a controlled manner under an external magnetic field, and are suitable for direct separation after biomolecule enrichment, and the magnetic microspheres have good biocompatibility. In addition to magnetic separation, It has excellent application value in technical fields such as targeted drug delivery and cell culture.

Description of drawings

Figure 1 is a schematic diagram of the process of preparing hedgehog-shaped magnetic microspheres.

FIG. 2 is a scanning electron microscope topography diagram of a sample prepared under the conditions of Example 1 of the present invention. Figure a is a magnetic nanoparticle, Figure b is a silica-wrapped magnetic nanoparticle, and Figure c is a hedgehog-shaped magnetic microsphere. The scale bar in the figure is 100 nm.

FIG. 3 is a topography diagram of a transmission electron microscope of a sample prepared under the conditions of Example 1 of the present invention. Figure a is a magnetic nanoparticle, Figure b is a silica-wrapped magnetic nanoparticle, and Figure c is a hedgehog-shaped magnetic microsphere. The scale bar in the figure is 100 nm.

Detailed ways

The above-mentioned content of the present invention will be described in further detail below through the form of examples, but it should not be understood that the scope of the above-mentioned subject matter of the present invention is limited to the following examples, and all technologies realized based on the above-mentioned content of the present invention belong to the present invention. scope of invention.

The experimental methods used in the following examples are conventional methods unless otherwise specified, and the reagents, methods and equipment used are conventional reagents, methods and equipment in the technical field unless otherwise specified.

Example 1

(1) Preparation of magnetic nanoparticles:

Get 16ml ethylene glycol solution, add 0.26g anhydrous ferric chloride, 1.2g sodium acetate, 0.4g poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (molar ratio 1:1), 0.004g L-ascorbic acid and 40ul ultrapure water, vigorously stir to form a brown mixed solution. 0.24 g of sodium hydroxide was added to the mixed solution, and stirring was continued for 30 min to obtain a brown transparent solution. It was transferred to a 20ml reaction kettle, and calcined at 190°C for 9h by hydrothermal method to obtain magnetic nanoparticles. The product was washed three times with a 1:1 mixture of ethanol and water, and then three times with ultrapure water.

(2) Preparation of silica-wrapped magnetic nanoparticles:

Disperse 6ml of the above magnetic nanoparticles in 40ml of ethanol, add 2ml of ammonia water, ultrasonically disperse for 15min, slowly add 200ul of tetraethyl orthosilicate dropwise in a water bath at 50°C, and stir at 600r for 1h to collect the silica-coated magnetic nanoparticles. , washed three times with ethanol and water respectively.

(3) Preparation of hedgehog-shaped magnetic microspheres:

0.0714g of magnesium chloride and 0.5349g of ammonium chloride were weighed and dispersed in 30ml of ultrapure water, mixed with 0.05g of the above silica-wrapped magnetic nanoparticles, 350ul of ammonia water was added, and ultrasonically dispersed for 30min. It was transferred to a 20ml reaction kettle and calcined at 140°C for 14h to obtain hedgehog-shaped magnetic microspheres.

Example 2

(1) Preparation of magnetic nanoparticles:

Get 16ml ethylene glycol solution, add 0.26g anhydrous ferric chloride, 1.2g sodium acetate, 0.4g poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (molar ratio 1:1), 0.004g L-ascorbic acid and 100ul ultrapure water, vigorously stir to form a brown mixed solution. 0.24 g of sodium hydroxide was added to the mixed solution, and stirring was continued for 30 min to obtain a brown transparent solution. It was transferred to a 20ml reaction kettle, and calcined at 190°C for 9h by hydrothermal method to obtain magnetic nanoparticles. The product was washed three times with a 1:1 mixture of ethanol and water, and then three times with ultrapure water.

(2) Preparation of silica-wrapped magnetic nanoparticles:

Disperse 6ml of the above magnetic nanoparticles in 40ml of ethanol, add 2ml of ammonia water, ultrasonically disperse for 15min, slowly add 200ul of tetraethyl orthosilicate dropwise in a water bath at 50°C, and stir at 600r for 1h to collect the silica-coated magnetic nanoparticles. , washed three times with ethanol and water respectively.

(3) Preparation of hedgehog-shaped magnetic microspheres:

0.0714g of magnesium chloride and 0.5349g of ammonium chloride were weighed and dispersed in 30ml of ultrapure water, mixed with 0.05g of the above silica-wrapped magnetic nanoparticles, 350ul of ammonia water was added, and ultrasonically dispersed for 30min. It was transferred to a 20ml reaction kettle and calcined at 140°C for 14h to obtain hedgehog-shaped magnetic microspheres.

Example 3

(1) Preparation of magnetic nanoparticles:

Get 16ml ethylene glycol solution, add 0.26g anhydrous ferric chloride, 1.2g sodium acetate, 0.4g poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (molar ratio 1:1), 0.004g L-ascorbic acid and 40ul ultrapure water, vigorously stir to form a brown mixed solution. 0.24 g of sodium hydroxide was added to the mixed solution, and stirring was continued for 30 min to obtain a brown transparent solution. It was transferred to a 20ml reaction kettle, and calcined at 190°C for 9h by hydrothermal method to obtain magnetic nanoparticles. The product was washed three times with a 1:1 mixture of ethanol and water, and then three times with ultrapure water.

(2) Preparation of silica-wrapped magnetic nanoparticles:

Disperse 6ml of the above magnetic nanoparticles in 40ml of ethanol, add 2ml of ammonia water, ultrasonically disperse for 15min, slowly add 200ul of tetraethyl orthosilicate dropwise in a water bath at 50°C, stir vigorously for 20min, and slowly add 200ul of tetraethylorthosilicate dropwise again. Ethyl ester, stirring at 600 r for 1 h to collect magnetic nanoparticles wrapped with silica, and washed with ethanol and water three times respectively.

(3) Preparation of hedgehog-shaped magnetic microspheres:

0.0714g of magnesium chloride and 0.5349g of ammonium chloride were weighed and dispersed in 30ml of ultrapure water, mixed with 0.05g of the above silica-wrapped magnetic nanoparticles, 350ul of ammonia water was added, and ultrasonically dispersed for 30min. It was transferred to a 20ml reaction kettle and calcined at 140°C for 14h to obtain hedgehog-shaped magnetic microspheres.

Example 4

(1) Preparation of magnetic nanoparticles:

16ml of ethylene glycol solution, followed by adding 0.26g anhydrous ferric chloride, 1.2g sodium acetate, 0.4g poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (molar ratio 1:1), 0.004 g L-ascorbic acid and 40ul ultrapure water, vigorously stir to form a brown mixed solution. 0.24 g of sodium hydroxide was added to the mixed solution, and stirring was continued for 30 min to obtain a brown transparent solution. It was transferred to a 20ml reaction kettle, and calcined at 190°C for 9h by hydrothermal method to obtain magnetic nanoparticles. The product was washed three times with a 1:1 mixture of ethanol and water, and then three times with ultrapure water.

(2) Preparation of silica-wrapped magnetic nanoparticles:

Disperse 6ml of the above magnetic nanoparticles in 40ml of ethanol, add 2ml of ammonia water, ultrasonically disperse for 15min, slowly add 200ul of tetraethyl orthosilicate dropwise in a water bath at 50°C, stir vigorously for 20min, and slowly add 200ul of tetraethylorthosilicate dropwise again. Ethyl ester, stirring at 600 r for 1 h to collect magnetic nanoparticles wrapped with silica, and washed with ethanol and water three times respectively.

(3) Preparation of hedgehog-shaped magnetic microspheres:

0.0714g of magnesium chloride and 0.5349g of ammonium chloride were weighed and dispersed in 30ml of ultrapure water, mixed with 0.1g of the above silica-coated magnetic nanoparticles, 350ul of ammonia water was added, and ultrasonically dispersed for 30min. It was transferred to a 20ml reaction kettle and calcined at 140°C for 14h to obtain hedgehog-shaped magnetic microspheres.

The above are only preferred embodiments of the present invention, and do not limit the present invention in any form. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, according to the technical essence of the present invention, Any simple modifications, equivalent replacements and improvements made in the above embodiments still fall within the protection scope of the technical solutions of the present invention.

Claims (8)

1. A preparation method of hedgehog shaped magnetic microsphere is characterized in that: the method comprises the following steps:

(1) Preparing magnetic nanoparticles:

adding anhydrous ferric trichloride, sodium acetate, poly (4-styrenesulfonic acid-co-maleic acid) sodium salt, L-ascorbic acid and a proper amount of water into an ethylene glycol solution in sequence, and stirring to form a mixed solution; adding sodium hydroxide into the mixed solution, and continuously stirring to obtain a brown transparent solution; transferring the magnetic nanoparticles into a reaction kettle, and obtaining magnetic nanoparticles by a one-step hydrothermal method;

(2) Preparing the silica-coated magnetic nanoparticles:

dispersing the magnetic nanoparticles in ethanol, adding ammonia water, performing ultrasonic dispersion, slowly dropwise adding tetraethyl orthosilicate under the condition of a water bath at 50 ℃, stirring for 1h, and collecting the magnetic nanoparticles coated by silicon dioxide;

(3) Preparing hedgehog magnetic microspheres:

preparing a mixed solution of magnesium chloride and ammonium chloride, uniformly mixing the mixed solution with the magnetic nano particles wrapped by the silicon dioxide, adding ammonia water, and performing ultrasonic dispersion; transferring the hedgehog magnetic microsphere into a reaction kettle, and obtaining the hedgehog magnetic microsphere by a one-step hydrothermal method.

2. The method of preparing the hedgehog shaped magnetic microsphere of claim 1, wherein: the volume ratio of the glycol solution in the step (1) to a proper amount of water is 160:1 to 800:1.

3. the method of preparing the hedgehog shaped magnetic microsphere of claim 1, wherein: the size of the magnetic nanoparticles prepared in the step (1) can be changed by adjusting the water adding amount: when the water addition amount is reduced or increased, the magnetic nano particles can be correspondingly reduced or enlarged.

4. The method of preparing the hedgehog shaped magnetic microsphere of claim 1, wherein: the hedgehog shaped magnetic microspheres of the step (3) can change the size of the microspheres by adjusting the adding amount of the tetraethyl orthosilicate of the step (2): by decreasing or increasing tetraethyl orthosilicate, the hedgehog shaped magnetic microspheres will shrink or enlarge accordingly.

5. The method of preparing the hedgehog shaped magnetic microsphere of claim 1, wherein: the hydrothermal method in the step (1) is carried out for 9 hours at 190 ℃.

6. The method of preparing the hedgehog shaped magnetic microsphere according to claim 1, wherein: the hydrothermal method in the step (3) is carried out for 14 hours at 140 ℃.

7. The hedgehog-shaped magnetic microsphere prepared by the method according to any one of claims 1 to 6, wherein the shell is magnesium silicate, has a nano needle structure, and is shaped like hedgehog; the inner core is magnetic ferroferric oxide nano particles and has good magnetic responsiveness.

8. The hedgehog shaped magnetic microsphere of claim 7, wherein: the particle size of the core magnetic ferroferric oxide nano particle is 60-90nm, and the particle size of the magnetic microsphere is 250-300nm.

Images