CN101923932A - Multifunctional double-layer core-shell structure magnetic nano particle, preparation method and application thereof - Google Patents
Multifunctional double-layer core-shell structure magnetic nano particle, preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a multifunctional double-layer core-shell structure magnetic nano particle. In the invention, a magnetic nano particle with a particle size of 1-300 nm is used as a core and coated with a double-layer shell consisting of a SiO2 layer with a thickness of 1-200 nm and a hydrolyzed silane coupling agent layer is 1-100 nm thick and comprises one or more multifunctional groups; the particle size and the shell layer thickness can be controlled through regulating the volumes, the weight ratios and the reaction time of the magnetic core, a silicon dioxide precursor, a silane coupling agent and a catalyst in a preparation process; the total particle size of the nano particle can be as small as 5-50 nm and as large as 700-800 nm; the nano particle can have superparamagnetism, paramagnetism and ferromagnetism according to the change of the magnetic core particle size; and one or more bioactive molecules can be connected into the shell layer of the magnetic nano particle or to the surface of the shell layer through a chemical method or a physical method. The invention also provides a preparation method of the multifunctional double-layer core-shell structure magnetic nano particle and application thereof. The particle preparation method has the advantages of simplicity, moderate condition, low cost and easy realization of industrial production. The nano particle can obtain different functions through connecting different bioactive molecules and can be applied to the fields of protein enrichment, biological detection, separation and purification, targeted drug carriers, cell imaging and medical imaging.
Description
Technical field
The invention belongs to material and biomedicine field, relate to a kind of multifunctional double-layer shell-core structure magnetic nano-particle and its production and application.
Background technology
Magnetic nano-particle has broad application prospects in fields such as biological detection and separation and purification, medical science radiography, target medicine carrier, environment measurings.These application requirements magnetic nano-particles have good chemical stability, dispersiveness and biocompatibility, narrower particle size distribution and higher magnetic responsiveness will satisfy these application requirements and must carry out the introducing of necessary chemistry coating, modification and proper function group to the magnetic nano particle sub-surface.
SiO
2Have good chemical stability, biocompatibility and anti-capacity of decomposition, the surface is electronegative simultaneously.Coat one deck SiO in the magnetic nano particle sub-surface
2After, can not only effectively shield the interaction of magnetic dipole, greatly reduce its ZETA current potential, increase between the particle coulomb repulsion power, it is dispersed well to make that nano particle has, and greatly strengthens the chemical stability and the biocompatibility of magnetic nano-particle, reduces its bio-toxicity.While SiO
2There is hydroxyl in the surface, further biological functional.Therefore, the SiO of difference in functionality base group modification
2The coated magnetic nano particle shows tempting application prospect in material, biology, medicine and other fields.
Present research mainly concentrates on the individual layer SiO of difference in functionality base group modification
2The preparation of the magnetic nanoparticle of shell-core structure and the application in material, biology, field of medicaments thereof.But various bioactive molecules are with being connected in same shell or surface, interact easily between different molecular and the functional group and influence its correlated performance, as connection amount, stability, fluorescent quenching etc.Therefore, the synthetic good dispersion of design, the stable double shells-core-shell structure magnetic nano particle that has that contains a large amount of organic functions groups high, that joint efficiency is high, structure is controlled show wide application prospect in fields such as material, biological medicines.Recently, also there is a small amount of research to report SiO
2The magnetic nano-particle of double-deck shell-core structure, but mainly concentrate on titanium dioxide silicon-metal and metal oxide, polymer-SiO
2And the report of two silica shell structures, utilize hydro thermal method with SnO as people such as Lou
2Be deposited on the magnetic nuclear surface that has coated silicon dioxide, particle (the Adv.Mater.2007 that has prepared bivalve-magnetic nuclear structure with cocoon shape structure, 19,3328), people such as Tang Huili coat silicon dioxide layer outside magnetic nuclear after, outside silicon dioxide layer, coat one deck inorganic, metal oxide again, prepare silicon dioxide-metal oxide bivalve-magnetic nuclear structure nano particle and increased its stability (Chinese invention patent application number: 200610147251), people such as Li have synthesized a kind of bivalve-nuclear magnetism nano particle (Chem.Phys.Lett.2008 with sandwich structure, 461,114), magnetic nuclear can be coated on different SiO respectively with fluorescent probe molecule
2In the shell, avoid the generation of fluorescent quenching.People such as Ma have prepared two SiO
2The magnetic nanoparticle of shell, and fluorescent material is embedded in the shell, its photoluminescent property can effectively be strengthened.(Chem.Mater.2006，18，1920)。People such as Rui have then prepared the PEG-SiO that internal layer has been modified polyethylene glycol
2The magnetic nanoparticle of shell (Langmuir, 2008,24,11189).Up to the present, yet there are no outer hydrolysis silane coupler for multiple functional group modification, internal layer is SiO
2, examine report with double shells-core-shell structure magnetic nano particle and preparation and application for magnetic nano-particle.
The SiO that the various silane couplers of report are modified before being different from
2The magnetic nano-particle of shell-core structure, the multifunctional double-layer shell-core structure magnetic nano-particle that the present invention reported has typical shell-shell-core double-layer shell-core structure, regular shape, big or small homogeneous (concrete structure with reference to the accompanying drawings 1).Wherein contain a large amount of organic functions groups in the hydrolysis silane coupler outer shell that functional group is modified, can efficiently connect various bioactive molecules; Different bioactive molecules can mix or be connected in the different shells respectively or shell surperficial, can effectively avoid influencing each other between them, improve its correlated performance.Has important application prospects in fields such as protein enrichment, biological detection and separation and purification, target medicine carrier, cell imaging, medical science radiography and environment measurings.
Summary of the invention
The purpose of this invention is to provide that a kind of preparation method is simple, stability is high, joint efficiency is high, good biocompatibility, the magnetic nano-particle that has wide range of applications and its production and application with multifunctional double-layer shell-core structure.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention is that the magnetic nanoparticle with particle diameter 1-300nm is a nuclear, and the outside is respectively the SiO of 1-200nm with thickness
2Layer and thickness are that the hydrolysis silane coupling agent layer double shells that contains one or more functional groups of 1-100nm coats, the total particle diameter I of nano particle is to 5-50nm, greatly can be to 700-800nm, its magnetic can have superparamagnetism, paramagnetism and ferromagnetism according to the variation in magnetic karyosome footpath.
Magnetic nanoparticle is meant nanometer iron, Fe
3O
4, γ-Fe
2O
3And one or more of other metallic iron oxysomes such as nickel-zinc ferrite, manganese-zinc ferrite, nickel-copper-zinc ferrite, the preferred amino silicane coupling agent of silane coupler, epoxy silane coupling, mercaptosilane coupling agents, unsaturated double-bond silane coupler, polyethylene glycol silane coupler.Functional group is meant organo-functional group and the polymer with chemical reactivity, preferred amino, carboxyl, hydroxyl, epoxy radicals, aldehyde radical, sulfydryl, unsaturated double-bond, phosphate, halogen, ester group, N-succinimido, dimaleoyl imino, ethylenediamine triacetic acid alkyl, polyethylene glycol, polyaminoacid, glycan.Catalyst refers to the compound of energy catalysis silicon dioxide presoma and silane coupler hydrolysis, one or more in preferred ammoniacal liquor, organic amine compound, NaOH, the potassium hydroxide.The silicon dioxide presoma refers to that the energy hydrolytie polycondensation becomes the compound of network of silica, preferred tetraethoxysilane, methyl silicate.
The particle size of multifunctional double-layer shell-core structure magnetic nano-particle of the present invention and shell thickness can be controlled by volume, weight ratio and the reaction time of regulating magnetic nuclear, silicon dioxide presoma, silane coupler, catalyst in the preparation process.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention can mix one or more bioactive molecules respectively or is connected in the different shells or the shell surface by chemistry or physical method.Said bioactive molecule refers to any can being connected in the nano particle shell or the material on surface by chemistry or physical method, comprises fluorescence probe, organic dyestuff, quantum dot, medicine, antibody, part, polymer, albumen, DNA, RNA, biotin, Avidin, enzyme, metal ion, crystal etc.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention can be prepared by following method:
After the magnetic nanoparticle process surfactant processing with different-grain diameter, coat layer of silicon dioxide by the hydrolysis of catalyst silicon dioxide presoma in the magnetic nano particle sub-surface, coat the hydrolysis silane coupling agent layer of one or more organic functions base group modifications of one deck again by catalyst at silica surface.The hydrolysis silane coupling agent layer that wherein is coated on one or more organic functions base group modifications of silica surface can get by catalyst silane coupler or ligand modified silane coupler hydrolysis, perhaps coat one deck hydrolysis silane coupling agent layer by the hydrolysis of catalyst silane coupler at silica surface earlier, make with ligand coupling again.
Concrete steps are as follows:
Route one:
(1) magnetic nanoparticle of different-grain diameter is joined in the aqueous surfactant solution of letting nitrogen in and deoxidizing after single dispersion treatment, be dispersed in organic solvent/aqueous solution, add catalyst and silicon dioxide presoma, coat layer of silicon dioxide in the magnetic nano particle sub-surface by the hydrolysis of catalyst silicon dioxide presoma.
(2) in the magnetic nano-particle dispersion liquid of above-mentioned coating layer of silicon dioxide, the silane coupler that adds catalyst and one or more organic functions base group modifications, coat the hydrolysis silane coupling agent layer that one deck contains one or more functional groups by catalyst silane coupler or ligand modified silane coupler hydrolysis again at the silicon dioxide laminar surface, make multifunctional double-layer shell-core structure magnetic nano-particle.
Route two: on route one step (1) basis of invariable, step (2) can be taked following operation: with method one step
(1) gained coats in the magnetic nano-particle dispersion liquid of layer of silicon dioxide, add catalyst and silane coupler, coat one deck hydrolysis silane coupling agent layer by the hydrolysis of catalyst silane coupler at the silicon dioxide laminar surface, with ligand coupling, make multifunctional double-layer shell-core structure magnetic nano-particle again.
Respectively going on foot feature among the above various preparation methods of the present invention is magnetic nano-particle is distributed to water after with deionized water or organic solvent washing, obtain the magnetic nano-particle dispersion liquid in organic solvent or water/organic solvent mixed solution, behind the ultrasonic dispersion 1-60min, add surfactant, catalyst, the silicon dioxide presoma, silane coupler, part, in the bioactive molecule one or more, wherein catalyst and silicon dioxide presoma, volume ratio or weight ratio between catalyst and the silane coupler are 1-100: 1-100, and at 10-180 ℃ of mechanical agitation or ultrasonic 1-48 hour intermittence.Magnetic separates or the centrifugation product, and product is with deionized water or organic solvent washing.
Organic solvent refers to various organic solvents, one or more in preferred alcohol, methyl alcohol, ethylene glycol, propyl alcohol, 2-propyl alcohol, the acetone described in the above various preparation methods of the present invention.Surfactant is meant the compound that changes magnetic particle surface character, one or more in preferred saturated or unrighted acid, citric acid, phosphoric acid, polycarboxylic acids and the salt thereof.Catalyst refers to the compound of energy catalysis silicon dioxide presoma and silane coupler hydrolysis, one or more in preferred ammoniacal liquor, organic amine compound, NaOH, the potassium hydroxide.The silicon dioxide presoma refers to that the energy hydrolytie polycondensation becomes the compound of network of silica, preferred tetraethoxysilane, methyl silicate.Silane coupler refers to the silane coupler of various band difference in functionality groups, preferred amino silicane coupling agent, epoxy silane coupling, mercaptosilane coupling agents, unsaturated double-bond silane coupler, polyethylene glycol silane coupler.Functional group is meant organo-functional group and the polymer with chemical reactivity, preferred amino (primary amine groups), carboxyl, hydroxyl, epoxy radicals, aldehyde radical, sulfydryl, unsaturated double-bond, phosphate, halogen, ester group, N-succinimido, dimaleoyl imino, ethylenediamine triacetic acid alkyl, polyethylene glycol, polyaminoacid, glycan.Part refer to contain one or more functional groups can with the organic compound of silane coupler coupling, preferred ethylenediamine triacetic acid acetaldehyde, polyethylene glycol, polyaminoacid, glycan, polyacrylate.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention can be applicable to protein enrichment, separation and purification and field of biological detection.Owing to contain a large amount of difference in functionality groups in the nanometer magnetic particle shell, can will have the part of specific enrichment, separation and purification function or bioactive molecule by physics or chemical method is entrained in the multifunctional double-layer shell-core structure magnetic nano particle subshell or is connected in the shell surface, magnetic separates after adding the material for the treatment of enrichment, separation and purification and detection, can reach the purpose of fast enriching, separation and purification and raising detectability.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention can be applicable to the target medicine carrier field.Because the magnetic nano-particle of multifunctional double-layer shell-core structure has good dispersiveness, chemical stability and biocompatibility, and lower bio-toxicity, contain a large amount of different functional groups in the nanometer magnetic particle shell simultaneously, in the application of target medicine carrier, demonstrate application prospects.Can be entrained in drug molecule in the multifunctional double-layer shell-core structure magnetic nano particle subshell or be connected in the shell surface by physics or chemical method, can also utilize nanoparticle surface rich functions group, again different bioactive molecules are connected with nano particle, can make medicine in lesions position enrichment and slowly release by externally-applied magnetic field, effectively reduce the toxic and side effect of medicine, reduce drug dose, reach the purpose of target transportation medicine and treatment disease.
Multifunctional double-layer shell-core structure magnetic nano-particle of the present invention can be applicable to cell imaging, medical science radiography field.Can make full use of a large amount of difference in functionality groups that contain in the nanometer magnetic particle shell, to have the part of fluorescence, radiography function or bioactive molecule by physics or chemical method and be entrained in the multifunctional double-layer shell-core structure magnetic nano particle subshell or be connected in the shell surface, and make it have the function of cell imaging, medical science radiography.
Generally speaking, the invention provides that a kind of preparation method is simple, stability is high, joint efficiency is high, good biocompatibility, the magnetic nano-particle that has wide range of applications and its production and application with multifunctional double-layer shell-core structure.This particle preparation method is simple, and mild condition is with low cost, easily realizes suitability for industrialized production.Their particle size and shell thickness can be controlled by regulating magnetic nuclear particle, silicon dioxide presoma, silane coupler, catalyst consumption and concentration ratio, reaction time, directly change according to the magnetic karyosome, its magnetic can have superparamagnetism and paramagnetism and ferromagnetism.The magnetic nano-particle of this double-deck shell-core structure not only makes nano particle have good dispersiveness, chemical stability and biocompatibility by the silicon dioxide layer that coats, effectively reduce its bio-toxicity, magnetic nuclear and extraneous and outer functional group or bioactive molecule effectively can also be separated, avoid its interaction and influence its correlated performance.The hydrolysis silane coupling agent layer that functional group is modified contains a large amount of functional groups, can efficiently connect one or more bioactive materials; In addition, also, effectively increase joint efficiency, avoid their interactions and influence its correlated performance to be entrained in its shell at the same time or separately by chemistry or physical method bioactive materials as required or to be connected in the shell surface.The magnetic nano-particle of this double-deck shell-core structure can be given its difference in functionality by connecting different bioactive materials, can be applicable to protein enrichment, biological detection and separation and purification, target medicine carrier, cell imaging, medical science radiography and environment measuring etc., demonstrate wide application prospect in fields such as material, biology, medical science.
Description of drawings
Fig. 1. amino functional base group modification double shells among the embodiment 1-core-shell structure magnetic nano particle TEM photo.
Fig. 2. the magnetic hysteresis loop of amido modified double shells-core-shell structure magnetic nano particle among the embodiment 2.
Fig. 3. have the fluorescence spectrum of the multifunctional double-layer shell-core structure magnetic nano-particle of photoluminescent property among the embodiment 3.
Fig. 4. MALDI-TOF mass spectrogram (a) beta-casein digestive juice (10 among the embodiment 5
-7M); (b) Fe
3+Beta-casein digestive juice (10 after the enrichment of-HEDTA-NP magnetic particle
-7M).
Embodiment
Embodiment 1 amino functional base group modification double shells-core-shell structure magnetic nano particle (AN-NP)
(1) ferriferrous oxide nano-particle with 60 μ g particle diameter 5-10nm washs the final vacuum drying with deionized water, acetone.Join the 0.3molL of 200mL again through letting nitrogen in and deoxidizing
-1In the surfactant solution, in 60 ℃ of nitrogen atmospheres, stir 12h behind the ultrasonic dispersion 30min.After system is cooled to room temperature, utilize magnet that product magnetic is separated at last, be distributed in the ethanol/water solution after the acetone washing.
(2) add ammoniacal liquor and tetraethoxysilane (volume ratio 10: 3) after getting the ultrasonic 30min of magnetic nano-particle dispersion liquid of above-mentioned (1) preparation, 40 ℃ of following mechanical agitation 12h, centrifugation product, product are dispersed in the ethanol/water after with the ethanol washing, make individual layer SiO
2The dispersion liquid of shell-core structure magnetic nano particle.
(3) add ammoniacal liquor and amino silicane coupling agent KH550 (volume ratio 1: 1) after getting the ultrasonic 30min of magnetic nano-particle dispersion liquid of above-mentioned (2) preparation, 40 ℃ of following mechanical agitation 12h, magnetic separates or the centrifugation product, after product is used ethanol, deionized water wash respectively, make double shells-core-shell structure magnetic nanoparticle with amino group modification.
Embodiment 2 second two nitrilotriacetic acid functional groups are modified double shells-core-shell structure magnetic nano particle (HEDTA-NP)
The magnetic nano-particle of getting (3) preparation among the embodiment 1 is distributed in the ethylene glycol solution, add second two nitrilotriacetic acid acetaldehyde behind the ultrasonic 30min, with itself and magnetic nanoparticle coupling, make double shells-core-shell structure magnetic nanoparticle by Schiff reaction with the modification of second two nitrilotriacetic acid functional groups.
Embodiment 3 has the preparation of the multifunctional double-layer shell-core structure magnetic nano-particle of photoluminescent property
Add ammoniacal liquor, amino silicane coupling agent G-KH550 and fluorescein sodium after getting the ultrasonic 30min of magnetic nano-particle dispersion liquid that (2) prepare among the embodiment 1, behind 60 ℃ of following mechanical agitation 12h, magnetic separates or the centrifugation product, product with ethanol after, make multifunctional double-layer shell-core structure magnetic nano-particle with photoluminescent property.
Embodiment 4 multifunction double-layer shell-core structure magnetic nano particles are as pharmaceutical carrier
Get the magnetic nano-particle of (3) preparation among the embodiment 1 and use ethanol respectively, behind the deionized water wash, be distributed in the deionized water solution, add glutaraldehyde solution after ultrasonic 5 minutes, ultrasonic reaction 1-2 hour intermittently under the room temperature, magnetic separates or the centrifugation product, product is respectively with behind the deionized water wash, again be dispersed in the phosphate buffer solution again, add the Doxorubicin aqueous solution, ultrasonic reaction 2-3 hour intermittently under the room temperature, by the Schiff reaction with Doxorubicin medicine and magnetic nanoparticle coupling, the separation of product magnetic, it is colourless to be washed till supernatant with pure water, makes to have the double shells-core-shell structure magnetic nanoparticle that carries the Doxorubicin medicine.
Embodiment 5 multifunction double-layer shell-core structure magnetic nano particle enrichments and detection phosphorylated protein
(1) gets the HEDTA-NP magnetic nano particle 1mg that makes among the embodiment 2 and be dispersed in the 1mL deionized water, made it to disperse fully in ultrasonic 5 minutes.Get in the test tube of above-mentioned dispersion liquid to a 2mL of 200 μ L, add the FeCl that is dissolved among the 1M HCl again
3Solution.Intermittently ultrasonic reaction is after 1 hour, and magnetic separates, and with 200 μ L 1M HCl washing nano particle twice, is dispersed among the 200 μ L1M HCl standby.
(2) to the Fe of above-mentioned gained
3O
4Add an amount of finite concentration (10 in the magnetic nano-particle
-7M or 10
-8M) cow's serum beta-casein digestive juice, after vibration mixed under the room temperature, the magnetic separated product was with 15%TFA (trifluoroacetic acid) acetonitrile solution (50%, v/v) fully wash three times, the gained magnetic nano-particle is scattered in an amount of 50% (v/v) acetonitrile solution (20 μ L).
(3) get an amount of above-mentioned dispersion liquid (0.5 μ L) and drip on the MALDI plate, and then drip the H of an amount of DHB (2, the 5-dihydroxy-benzoic acid) and 1% (v/v)
3PO
4The acetonitrile mixed solution, mix, carry out MALDI-TOFMS test after the crystallization of volatilizing then.
Claims (9)
1. multifunctional double-layer shell-core structure magnetic nano-particle is characterized in that the magnetic nanoparticle with particle diameter 1-300nm is a nuclear, and the outside is respectively the SiO of 1-200nm with thickness
2Layer and thickness are that the hydrolysis silane coupling agent layer double shells that contains one or more functional groups of 1-100nm coats, the total particle diameter I of nano particle is to 5-50nm, greatly can be to 700-800nm, its magnetic can have superparamagnetism, paramagnetism and ferromagnetism according to the variation in magnetic karyosome footpath; Wherein:
Magnetic nanoparticle is meant nanometer iron, Fe
3O
4, γ-Fe
2O
3And one or more of other metallic iron oxysomes such as nickel-zinc ferrite, manganese-zinc ferrite, nickel-copper-zinc ferrite; Silane coupler refers to the silane coupler of various band difference in functionality groups, preferred amino silicane coupling agent, epoxy silane coupling, mercaptosilane coupling agents, unsaturated double-bond silane coupler, polyethylene glycol silane coupler; Functional group is meant organo-functional group and the polymer with chemical reactivity, preferred amino, carboxyl, hydroxyl, epoxy radicals, aldehyde radical, sulfydryl, unsaturated double-bond, phosphate, halogen, ester group, N-succinimido, dimaleoyl imino, ethylenediamine triacetic acid alkyl, polyethylene glycol, polyaminoacid, glycan.
2. multifunctional double-layer shell-core structure magnetic nano-particle according to claim 1 is characterized in that the particle size of magnetic nano-particle and shell thickness can control by volume, weight ratio and the reaction time of regulating magnetic nuclear, silicon dioxide presoma, silane coupler, catalyst in the preparation process.
3. multifunctional double-layer shell-core structure magnetic nano-particle according to claim 1 is characterized in that and can one or more bioactive molecules be mixed respectively or is connected in the different shells or the shell surface by chemistry or physical method.
4. the preparation method of multifunctional double-layer shell-core structure magnetic nano-particle according to claim 1, after it is characterized in that magnetic nanoparticle process surfactant processing with different-grain diameter, coat layer of silicon dioxide by the hydrolysis of catalyst silicon dioxide presoma in the magnetic nano particle sub-surface, coat the hydrolysis silane coupling agent layer that one deck contains one or more functional groups at silica surface again, the hydrolysis silane coupling agent layer that contains one or more functional groups that wherein is coated on silica surface can get by catalyst silane coupler or ligand modified silane coupler hydrolysis, perhaps coat one deck hydrolysis silane coupling agent layer by the hydrolysis of catalyst silane coupler at silica surface earlier, make with ligand coupling again.
5. according to claim 3 and 4 described methods, it respectively goes on foot feature and is magnetic nano-particle is distributed to water after with deionized water or organic solvent washing, obtain the magnetic nano-particle dispersion liquid in organic solvent or water/organic solvent mixed solution, behind the ultrasonic dispersion 1-60min, add surfactant, catalyst, the silicon dioxide presoma, part, in the bioactive molecule one or more, wherein catalyst and silicon dioxide presoma, volume ratio and weight ratio between catalyst and the silane coupler are 1-100: 1-100, at 10-180 ℃ of mechanical agitation or ultrasonic 1-48h intermittently, magnetic separates or the centrifugation product, and product is with deionized water or organic solvent washing.
6. refer to various organic solvents according to claim 2,3,4 and 5 described organic solvents, one or more in preferred alcohol, methyl alcohol, ethylene glycol, propyl alcohol, 2-propyl alcohol, the acetone; Surfactant is meant the compound that changes magnetic particle surface character, one or more in preferred saturated or unrighted acid, citric acid, phosphoric acid, polycarboxylic acids and the salt thereof; Catalyst refers to the compound of energy catalysis silicon dioxide presoma and silane coupler hydrolysis, one or more in preferred ammoniacal liquor, organic amine compound, NaOH, the potassium hydroxide; The silicon dioxide presoma refers to that the energy hydrolytie polycondensation becomes the compound of network of silica, preferred tetraethoxysilane, methyl silicate; Silane coupler refers to the silane coupler of various band difference in functionality groups, preferred amino silicane coupling agent, epoxy silane coupling, mercaptosilane coupling agents, unsaturated double-bond silane coupler, polyethylene glycol silane coupler; Functional group is meant organo-functional group and the polymer with chemical reactivity, preferred amino, carboxyl, hydroxyl, epoxy radicals, aldehyde radical, sulfydryl, unsaturated double-bond, phosphate, halogen, ester group, N-succinimido, dimaleoyl imino, ethylenediamine triacetic acid alkyl, polyethylene glycol, polyaminoacid, glycan; Part refer to contain one or more functional groups can with the organic compound of silane coupler coupling, preferred ethylenediamine triacetic acid acetaldehyde, polyethylene glycol, polyaminoacid, glycan, polyacrylate; Bioactive molecule refers to and can be connected in the nano particle shell or the material on surface by chemistry or physical method, comprises fluorescence probe, organic dyestuff, quantum dot, medicine, antibody, part, polymer, albumen, DNA, RNA, biotin, Avidin, enzyme, metal ion, crystal.
7. multifunctional double-layer shell-core structure magnetic nano-particle is in the application of protein enrichment, separation and purification and field of biological detection.
8. multifunctional double-layer shell-core structure magnetic nano-particle is in the application in target medicine carrier field.
9. multifunctional double-layer shell-core structure magnetic nano-particle is in the application in cell imaging, medical science radiography field.
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