CN1217352C

CN1217352C - Nano/micron microsphere with superparamagnetism and preparation method

Info

Publication number: CN1217352C
Application number: CN 03100891
Authority: CN
Inventors: 刘先桥; 刘会洲; 邢建民; 张冠东
Original assignee: Institute of Process Engineering of CAS
Current assignee: Institute of Process Engineering of CAS
Priority date: 2003-01-24
Filing date: 2003-01-24
Publication date: 2005-08-31
Anticipated expiration: 2023-01-24
Also published as: CN1519866A

Abstract

The invention belongs to the field of superparamagnetic functional microspheres, in particular to superparamagnetic nano/micro microspheres and a method for preparing superparamagnetic nano/micro microspheres by silanization. The surface of freshly prepared Fe ₃ O ₄ nanoparticles is coated with SiO ₂ with different contents and layers to achieve the effect of controlling the particle size of the microspheres and preventing agglomeration, and then under relatively mild conditions, the magnetic properties of the silicon-coated The surface of the microsphere is silanized to obtain a kind of superparamagnetic microsphere with functional groups on the surface. The particle diameter of the microsphere is between 30nm-1000nm/1-20μm, and the weight percentage of the magnetic Fe ₃ O ₄ in the whole microsphere is between 0.5-60%. Magnetic microspheres have controllable particle size, good spheroidization, uniform size, uniform magnetic content among different spheres, and stable physical and chemical properties.

Description

Super-paramagnetism nano/micron microballoon and preparation method thereof

Technical field

The invention belongs to superparamagnetism functional microsphere field, particularly super-paramagnetism nano/micron microballoon and silanization thereof prepare the method for super-paramagnetism nano/micron microballoon.

Background technology

The particularly nano level magnetic function microballoon of magnetic microsphere, but bioactivators such as its surface chemical coupling enzyme, antibody, antigen utilize its superparamagnetism simultaneously, promptly in externally-applied magnetic field, can produce magnetic, after the external magnetic field disappeared, no remanent magnetism was realized fast and convenient isolate reactant.Have tempting application prospect at biomedical sectors such as immobilised enzymes, immune detection, protein purification, target administration, stem cell separation, belong to the field, forward position of current subject.

The method of the synthetic superparamagnetism microballoon of prior art mainly contains investment, monomer copolymerization method, chemical transformation, polymer chemistry reaction method and silanization method.Wherein investment is that magnetic particle is scattered in the biological macromolecule solns, obtains magnetic microsphere by means such as crosslinked, atomizing, flocculation, deposition, evaporations.This method granular biological compatibility simple to operate, preparation is good; But the gained grain shape is irregular, and granular size is wayward, particle size distribution is wide, is mixed with the impurity of emulsifying agent and so in the shell, makes to use to be very restricted.The monomer copolymerization method normally adopts two or more monomer (wherein a kind of is function monomer), polymerization reaction under certain condition, generate the magnetic microsphere of surface band functional group, mainly comprise emulsion (soap-free emulsion) polymerization, suspension polymerisation, dispersin polymerization, seeding polymerization and radiation polymerization.The magnetic microsphere better performances that this method is synthetic, but the content of function monomer is restricted (usually less than 10%), most of functional group is covered by microballoon inside, severe reaction conditions, and synthesis technique is very loaded down with trivial details.Chemical transformation is meant certain density magnetic metal ion infiltration and exchanges in the macroreticular resin and goes, utilize chemical reaction to make metal ion be converted into magnetic metal oxide then, make it to be evenly distributed in the pore structure of polymer, infiltration and step of converting can carry out repeatedly.This method is simple to operate, and magnetic is evenly distributed, and magnetic content is controlled easily, but relatively stricter to the requirement of resin.The polymer chemistry reaction method is the high molecule magnetic microsphere that generates earlier not with functional group, be reflected at the activity functional groups that the magnetic microsphere surface produces high power capacity by surperficial polymer chemistry then, but these reactions are often carried out under the high temperature strong acidic condition, magnetic property to microballoon exerts an influence, cause inner inorganic magnetic particle to decompose, thereby limited the use of this method.The current Silicane Method that adopts is direct magnetic particle (Fe at hydroxyl ₃O ₄) surface carries out the magnetic microsphere of silanization Processing of Preparation band functional group with the silicone couplet of band functional group, this method preparation process is simple, surperficial functional group content height; But because magnetic particle (Fe ₃O ₄) particle diameter too little (about 8nm) itself, bunch (cluster) of 200-400nm reunited, usually formed to the magnetic Nano microsphere of preparation easily, and the size of particle is not easy to regulate, and the range of application of particle is restricted.

The Fe of acidization preparation surface bag silicon related to the present invention ₃O ₄Magnetic-particle is (referring to TheChinese Journal of Process Engineering, Vol.2. (4): 319-320).This method at first adopts coprecipitation to obtain the Fe of fresh deposition ₃O ₄Nano particle utilizes magnet to wash separation, is dispersed in through pretreated Na sedimentation products is ultrasonic ₂SiO ₃In the solution, drip HCl solution then in solution, the pH value that changes solution is isolated product to faintly acid, obtains the surface and is coated with SiO ₂Magnetic microsphere, A of the present invention, the B step has been used for reference this method, and innovates on this basis, prepares the microballoon of different-grain diameter.

The direct silanization method close with the present invention prepare the superparamagnetism microballoon (referring to Journal ofColloid and Interface Science, Vol.141 (2): be to utilize end to contain functional group 505-511) (as-NH ₂) silicone couplet and the magnetic particle of surperficial hydroxyl (as Fe ₃O ₄) carry out thermal dehydration, obtain the magnetic microsphere of silanization.Because the particle diameter of magnetic particle is too little, agglomeration is unavoidable in the course of reaction, and the grain shape that obtains is irregular, and there are some defectives in synthetic microballoon on performance, as part Fe ₃O ₄Particle is exposed, and the magnetic content of variable grain is big outside, and homogeneity is poor, reunites easily in actual applications, influences result of use.

Summary of the invention

One of purpose of the present invention is the deficiency that exists on the preparation magnetic microsphere at existing direct silanization method, it is controlled to propose a kind of microspherulite diameter, narrow diameter distribution, the superparamagnetism microballoon of preparing does not have agglomeration, and the stable silanization of chemical property prepares the method for super-paramagnetism nano/micron microballoon.

Another object of the present invention provides a kind of microspherulite diameter scalable, the super-paramagnetism nano of narrow diameter distribution/micron microballoon.

The present invention is (as Fe at inorganic particles with superparamagnetism ₃O ₄) outside wraps one or more layers silicon dioxide, thereby can change and control the size of magnetic-particle, form uniform magnetic microsphere, carry out back silanization processing again on bag silicon magnetic microsphere surface then.Can prepare different-grain diameter, adapt to multi-purpose superparamagnetism microballoon, and the generation of agglomeration in can avoiding using.

Main technical schemes of the present invention is: adopt acidization to prepare surperficial coated Si O earlier ₂The superparamagnetism microballoon, by changing SiO ₂And Fe ₃O ₄Ratio, repeat the microballoon that encapsulation steps can prepare different magnetic content and different-grain diameter, adopt improved Silicane Method then, utilize to have certain functional group (as-NH ₂) silicone couplet and the hydroxyl of above-mentioned microsphere surface by dehydration, form the Si-O-Si key, thereby obtain the superparamagnetism microballoon that the surface has functional group.This microspherulite diameter between 30-1000nm or 1 μ m-20 μ m, the Fe in the superparamagnetism microballoon ₃O ₄Nano particle diameter is about 8-15nm, magnetic Fe ₃O ₄Accounting for whole microballoon percentage by weight is between the 0.5-60%.Magnetic microsphere particle diameter controlled amount, balling-up are good, magnetic uniform content between the particle size distribution homogeneous, different ball, reaction condition gentleness, physical and chemical performance are stable.

The method that silanization prepares the superparamagnetism microballoon comprises that coprecipitation prepares the nano-scale magnetic particle, and acidization is at magnetic-particle surface coated Si O ₂With with various silicone couplets the magnetic microsphere of bag behind the silicon carried out silanization and handles.The particle size that it is characterized in that magnetic microsphere is adjustable, and particle balling preparation and good dispersion, no serious agglomeration, preparation technology are simple.

The method that silanization of the present invention prepares super-paramagnetism nano/micron microballoon mainly may further comprise the steps:

A. coprecipitation prepares superparamagnetism Fe ₃O ₄Nano particle

At 80-90 ℃, under the nitrogen protection, to containing Fe ²⁺And Fe ³⁺Molysite aqueous solution in impouring alkali lye, high-speed stirred is isolated sedimentation products with magnet, obtains fresh Fe ₃O ₄Nano particle.

B. acidization prepares surperficial coated Si O ₂Magnetic Fe ₃O ₄The Nano/micron microballoon

(1). the fresh Fe that step (A) is prepared ₃O ₄Nano particle, the ultrasonic Na that is dispersed in through preliminary treatment (the pH value being transferred to about 12-13 in advance) with hydrochloric acid ₂SiO ₃In the solution;

(2). the solution of step (1) is warming up to 80-90 ℃; under nitrogen protection and stirring condition, in solution, add hydrochloric acid or the sulfuric acid of the about 2mol/l of concentration, the pH value of solution is transferred to about 5-7 by alkalescence; isolate product and fully wash with magnet, obtain surperficial coated Si O with deionized water ₂Magnetic Fe ₃O ₄Nano microsphere;

(3). repeating step (2) can obtain different SiO ₂The magnetic Fe of the different-grain diameter of the covering amount and the coating number of plies ₃O ₄The Nano/micron microballoon;

C. super-paramagnetism nano/micron the microballoon of functional group is with on silanization preparation surface

(1). will join with the silicone couplet of functional group in methyl alcohol or the ethanol, wherein, the percent by volume of silicone couplet and methyl alcohol or ethanol is 10-20%, fully mixes;

(2). in the solution of step (1), add surperficial coated Si O ₂Magnetic Fe ₃O ₄The Nano/micron microballoon, wherein, surperficial coated Si O ₂Magnetic Fe ₃O ₄The mass percent of Nano/micron microballoon and solution is 0.5-5%, adds a spot of organic acid and water simultaneously, and wherein, the percent by volume of organic acid and solution is 1-10%, and the percent by volume of water and solution is 0.5-2%, ultrasonic 30-60min;

(3). the solution impouring of step (2) is filled in the container of glycerine, and wherein, the solution of step (2) and the volume ratio of glycerine are 1: 1-2, fully stir, be warmed up to 70-95 ℃ of reaction; After water in the question response thing and methyl alcohol or ethanol evaporate fully, stop reaction, fully wash with the product Magnetic Isolation and with deionized water.

Above-mentioned magnetic Fe ₃O ₄The preparation condition of nano particle is Fe in the molysite aqueous solution ²⁺And Fe ³⁺Mol ratio be 1: 2 to 1: 0, add the OH of alkali ^-With 2Fe in the molysite aqueous solution ²⁺+ 3Fe ³⁺The mol ratio of sum is 1: 0.1 to 1: 1.5; Described alkali is NH ₄OH, KOH, NaOH, Na ₂CO ₃Or NaHCO ₃

Above-mentioned silicone couplet is γ-An Jibingjisanyiyangjiguiwan (WD-50, KM-50, KH-550, A-1100), [γ (β-aminoethyl) aminopropyl] trimethoxy silane (WD-52, KM-52, A-1120), (γ-glycidyl ether) methoxy silane (WD-60, KM-60, KH-560, A-187), dodecyl triethoxysilane or n-hexane base trimethoxy silane (A-0800, A-0700, D-6224, H-7334).

Described organic acid is glacial acetic acid, phosphoric acid or other organic acid.

The method that silanization of the present invention prepares super-paramagnetism nano/micron microballoon compared with prior art, method of the present invention on preparation technology at first to magnetic Fe ₃O ₄Nano grain surface has carried out bag silicon to be handled, and makes original particle diameter less (about 10nm), the Fe that is easy to reunite ₃O ₄It is bigger that nano particle becomes particle diameter, and (30nm-1000nm/1-20 μ m) can regulate as required within the specific limits, promptly changes the coated Si O of institute by the simple encapsulation steps that repeats ₂Amount and coat the number of plies, thereby reach the purpose of control microspherulite diameter, the particle balling preparation of generation is good, the size homogeneous can effectively be avoided the generation of agglomeration.Existing Silicane Method is to adopt directly at Fe ₃O ₄Nano grain surface carries out silanization to be handled, and handles by the thermal dehydration of glycerine, and reaction temperature is utilized Fe at 170-180 ℃ ₃O ₄The Fe-OH group of nano grain surface generates the effect that the Fe-O-Si key plays the coupling function group.The present invention carries out the thermal dehydration reaction on the bag silicon magnetic microsphere surface that has the Si-OH group, form so-called Si-O-Si key at microsphere surface, and this reaction is easier to be carried out, and reaction condition is gentleer than original, and operation is more easy.Because at Fe ₃O ₄The surface has coated dense SiO ₂, the bead chemical property of generation is stable, and microballoon can be stablized and preserve more than several weeks in the hydrochloric acid or sulfuric acid of 3mol/L, not then dissolving fully in 30min of the naked powder of Bao Fuing.

Description of drawings

Fig. 1: the Fe of Bao Fuing not ₃O ₄Nano particle TEM figure.

Fig. 2: the surperficial coated Si O of the embodiment of the invention 5 ₂Silanization magnetic microsphere SEM figure.

Embodiment

Below by embodiment technical scheme of the present invention is described further:

Embodiment 1

Coprecipitation prepares magnetic Fe ₃O ₄Nano particle

In the 1 liter of stirring reactor that fills the 500ml deionized water, add 0.043 mole of FeCl ₂4H ₂O and 0.086 mole of FeCl ₃6H ₂O is warming up to 85-90 ℃ under nitrogen protection, impouring contains 0.478 mole of NH in the high-speed stirred process ₃H ₂The O aqueous solution, solution colour blackening at once utilizes magnetic field the product that deposits to be isolated and used respectively the NaCl of deionized water and 0.02M to wash once then.

The about 30g of above-mentioned magnetic agglomerate gross weight, wherein Fe ₃O ₄About 10g, transmission electron microscope observing Fe ₃O ₄Particle is bordering on sphere, has superparamagnetism, and average grain diameter is 8nm.

Embodiment 2

In filling 1 liter of stirring reactor of 700ml deionized water, add 0.21 mole of FeCl ₂4H ₂O and 0.31 mole of FeCl ₃6H ₂O is warming up to 70 ℃, and impouring 100ml contains 1 mole NaHCO ₃The aqueous solution, Magnetic Isolation incline supernatant get final product the Fe of prepared fresh ₃O ₄Nano particle.

The about 60g of above-mentioned magnetic agglomerate gross weight, wherein Fe ₃O ₄About 35g, transmission electron microscope observing Fe ₃O ₄Particle is bordering on sphere, has superparamagnetism, and average grain diameter is 15nm.

Embodiment 3

Acidization prepares SiO ₂The magnetic microsphere that coats

Calculate 10g Fe ₃O ₄Coat 20g SiO ₂Need corresponding N a ₂SiO ₃9H ₂The about 95g of O, preset Na ₂SiO ₃The pH value of solution is to 12-13

(1). the fresh Fe that embodiment 1 is prepared ₃O ₄Nano particle, ultrasonic being dispersed in through pretreated Na ₂SiO ₃In the solution.

(2). solution is warming up to 85 ℃, under the high-speed stirred condition, in solution, adds the hydrochloric acid of the about 2mol/l of concentration; The pH value of solution is transferred to about 5-7 by alkalescence, isolate product and use deionized water wash 3-4 time, drying with magnet.Obtain surperficial coated Si O ₂Magnetic microsphere, SiO ₂And Fe ₃O ₄Weight ratio be 2: 1.

Embodiment 4

Calculating coats 20g SiO again at the microsphere surface of embodiment 3 ₂Need Na ₂SiO ₃9H ₂The about 95g of O.

(1). with the fresh bag silicon grain that embodiment 3 prepares, the ultrasonic Na that is dispersed in ₂SiO ₃In the solution.

(2). solution is warming up to 85 ℃, under high-speed stirred (400-600rpm) condition, in solution, adds the hydrochloric acid of the about 2mol/l of concentration; The pH value of solution is transferred to about 5-7 by alkalescence, with magnet isolate product and with deionized water fully wash, drying, obtain the surface and coat two-layer SiO ₂Magnetic microsphere, SiO ₂And Fe ₃O ₄Weight ratio be 4: 1.

Fresh bag silicon grain repeating step (2) with preparing can obtain different SiO ₂The magnetic microsphere of the different-grain diameter of the covering amount and the coating number of plies.

Embodiment 5

Silanization method prepares the magnetic function microballoon

(1). get 10ml silicone couplet KH-550 and add in the 250ml absolute methanol, fully mix.

(2). in the solution of step (1), add the bag silicon magnetic microsphere of 2g embodiment 4,5ml glacial acetic acid or phosphoric acid and 2.5g water, ultrasonic 30-60min.

(3). the solution impouring of step (2) is filled in the 500ml there-necked flask of 200ml glycerine, fully stir, be warmed up to 75-80 ℃ of reaction 3-4 hour.

(4). fully wash 4-5 time with the product Magnetic Isolation and with deionized water, obtain surface band-NH ₂The silanization magnetic microsphere of group.Particle diameter is about 100nm.

Embodiment 6

(1). get 20g silicone couplet WD-52, add absolute ethyl alcohol, the solution 100ml of preparation 20wt%.

(2). in the solution of step (1), add the Fe of 1g embodiment 4 bag silicon ₃O ₄Magnetic microsphere, ultrasonic 20 minutes.

(3). the mixture adding of step (2) is filled in the 250ml there-necked flask of 200ml glycerine, stir, normal temperature reacts more than 12 hours down.

(4). product is fully washed 4-5 time with deionized water, and Magnetic Isolation is removed unreacted silicone couplet, obtains surface band-NH ₂The silanization magnetic microsphere of group.Particle diameter is about 100nm.

Embodiment 7

Acidization prepares SiO ₂The magnetic microsphere that coats

Calculate 10g Fe ₃O ₄Coat 40g SiO ₂Need corresponding N a ₂SiO ₃9H ₂The about 190g of O, preset Na ₂SiO ₃The pH value of solution is to 12-13

(1). the fresh Fe that embodiment 2 is prepared ₃O ₄Nano particle, ultrasonic being dispersed in through pretreated Na ₂SiO ₃In the solution.

(2). solution is warming up to 85 ℃, under the high-speed stirred condition, in solution, adds the sulfuric acid of the about 1mol/l of concentration; The pH value of solution is transferred to about 5-7 by alkalescence, isolate product and use deionized water wash 3-4 time with magnet, in dry.Obtain surperficial coated Si O ₂Magnetic microsphere, SiO ₂And Fe ₃O ₄Weight ratio be 4: 1.

Embodiment 8

Calculating coats 20g SiO again at the microsphere surface of embodiment 7 ₂Need Na ₂SiO ₃9H ₂The about 95g of O.

(1). with the fresh bag silicon grain that embodiment 7 prepares, the ultrasonic Na that is dispersed in ₂SiO ₃In the solution.

(2). solution is warming up to 85 ℃, under high-speed stirred (400-600rpm) condition, in solution, adds the sulfuric acid of the about 1mol/l of concentration; The pH value of solution is transferred to about 5-7 by alkalescence, with magnet isolate product and with deionized water fully wash, drying, obtain the surface and coat two-layer SiO ₂Magnetic microsphere, SiO ₂And Fe ₃O ₄Weight ratio be 6: 1.

Embodiment 9

Silanization method prepares the magnetic function microballoon

(1). get 10ml silicone couplet KM-50 and add in the 250ml absolute ethyl alcohol, fully mix.

(2). in the solution of step (1), add the bag silicon magnetic microsphere of 2g embodiment 8,5ml phosphoric acid and 3.0g water, ultrasonic 45-60min.

(3). the solution impouring of step (2) is filled in the 500ml there-necked flask of 200ml glycerine, fully stir, be warmed up to 70-75 ℃ of reaction 4-5 hour.

(4). fully wash 4-5 time with the product Magnetic Isolation and with deionized water, obtain surface band-NH ₂The silanization magnetic microsphere of group.Particle diameter is about 200nm.

Embodiment 10

(1). get 20g silicone couplet KM-52, add absolute methanol, the solution 100ml of preparation 20wt%.

(2). in the solution of step (1), add the Fe of 1g embodiment 8 bag silicon ₃O ₄Magnetic microsphere, ultrasonic 45-60 minute.

(3). the mixture adding of step (2) is filled in the 250ml there-necked flask of 200ml glycerine, stir, normal temperature reacts more than 14 hours down.

(4). product is fully washed 4-5 time with deionized water, and Magnetic Isolation is removed unreacted silicone couplet, obtains surface band-NH ₂The silanization magnetic microsphere of group.Particle diameter is about 200nm.

Claims

1. a method for preparing superparamagnetic nanometer/micron microspheres by silanization is characterized in that: the method for preparing superparamagnetic nanometer/micron microspheres by described silanization may further comprise the steps:

A. Preparation of Magnetic Fe ₃ O ₄ Nano/Microspheres Coated with SiO ₂ by Acidification Method

(1). The prepared fresh Fe ₃ O ₄ nanoparticles are ultrasonically dispersed in a Na ₂ SiO ₃ solution whose pH value is pre-adjusted to 12-13 with hydrochloric acid;

(2). Warm up the solution in step (1) to 80-90°C, under nitrogen protection and stirring conditions, add hydrochloric acid or sulfuric acid to the solution, adjust the pH value of the solution from alkaline to 5-7, separate The product is fully washed with deionized water _to obtain magnetic _Fe3O4 nanospheres coated with _SiO2 on the surface;

Repeat step (2) to obtain magnetic nano/micron microspheres of different particle sizes;

B. Preparation of superparamagnetic nano/microspheres with functional groups on the surface by silanization

(1). Add the silicon coupling agent with functional groups into methanol or ethanol, wherein the volume percentage of silicon coupling agent and methanol or ethanol is 10-20%, fully stir and mix evenly;

(2). In the solution of step (1), add surface coating SiO ₂ Magnetic Fe ₃ O ₄ nanometer/micron microspheres, wherein, surface coating SiO ₂ Magnetic Fe ₃ O ₄ nanometer/micron microspheres and solution The mass percentage is 0.5-5%, while adding a small amount of organic acid and water, wherein, the volume percentage of organic acid and solution is 1-10%, the volume percentage of water and solution is 0.5-2%, ultrasonic;

(3). Pour the solution in step (2) into a container containing glycerin, wherein the volume ratio of the solution in step (2) to glycerin is 1:1-2, stir well, and heat up to 70-95°C for reaction ; After the water and methanol or ethanol in the reactant are completely evaporated, the reaction is stopped, and the product is magnetically separated and fully washed with deionized water.

2. The method according to claim 1, characterized in that: the silicon coupling agent is γ-aminopropyl triethoxysilane, [γ (β-aminoethyl) aminopropyl] trimethoxy Silane, (γ-glycidyl ether)methoxysilane, n-dodecyltriethoxysilane or n-hexyltrimethoxysilane.

3. The method according to claim 1, characterized in that: said organic acid is glacial acetic acid or phosphoric acid.

4. The method according to claim 1, characterized in that: the ultrasonic time of the step B is 30-60min.

5. A superparamagnetic nano/micro microsphere prepared by the method according to any one of claims 1 to 4, characterized in that: the particle size of the microsphere is between 30-1000nm or 1 μm-20 μm .

6. The microsphere as claimed in claim 5, characterized in that: the _Fe3O4 nanoparticle diameter in the superparamagnetic nano/micron microsphere is _8-15nm , and the magnetic _Fe3O4 occupies _the entire microsphere The ball weight percentage is between 0.5-60%.