CN1667413A - Immune magnetic microsphere and preparing process and usage thereof - Google Patents
Immune magnetic microsphere and preparing process and usage thereof Download PDFInfo
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Abstract
This invention relates to an immunological magnetic microballoon, the process method of which comprises following steps: fully mixing oleic acid coating Fe3O4 magnetofluid and polymer monomer, cross linker and initiating agent to form oil phase; floating them in polyvinyl alcohol aqueous phase; polymerizing emulsion and suspension to process magnetic polymer microballoon; then introducing functional group on microballon surface through aminolysis reaction.The magnetic microballon is able to couple special immune genin on its surface, then these special immune genin further identify corresponding antibody, antigen and bioepiderm or directly use amidogen on immune magnetic microballon surface to identify antibody, antigen and bioepiderm able to react with amidogen.
Description
Technical field
The present invention relates to a kind of immune magnetic microsphere, and its production and use.
Background technology
The immune magnetic microsphere technology be immunology and magnetic carrier technology in conjunction with and a new technology growing up.It is a class new material that rises the seventies in 20th century.Immune magnetic microsphere is made up of inorganic magnetic carrier and macromolecule shell usually, and at the specific immune aglucon of its surface chemistry coupling such as albumen, antibody, antigen, agglutinin etc.Thereby these immune aglucons can further be discerned corresponding antibody, antigen, biotin etc. and reach separation or testing goal in reaction medium.Magnetic carrier has superparamagnetism, promptly can produce magnetic in externally-applied magnetic field, after the external magnetic field disappears, and no remanent magnetism.Immune magnetic microsphere has the characteristics of superparamagnetism and biospecificity simultaneously, makes Separation of Solid and Liquid more fast and convenient.Can save centrifugal.Numerous and diverse traditional operations such as filtration.In immune detection.Biomedical sector such as antibody purification, cell separation has tempting application prospect.
In the prior art, mostly immune magnetic microsphere is to make by activation swelling method or monomer copolymerization method.Danish Patent DE3836475 provides a kind of and has produced immune magnetic microsphere with the multistep swelling method, can obtain uniform particle.But the complex process of this patent, the equipment requirements height, productive rate is low.And, because to Fe
3O
4The size Control of particle requires tighter, is difficult to guarantee whole Fe
3O
4Particle size is less than 30nm, thereby has a small amount of remanent magnetism.The monomer copolymerization method normally adopts two or more monomer (wherein a kind of is function monomer), polyreaction generates the immune magnetic microsphere that functional group is with on the surface under certain condition, mainly comprises emulsion (soap-free emulsion) polymerization, suspension polymerization, dispersin polymerization and seeding polymerization.Chinese patent 92105584.6 adopts the monomer copolymerization legal system to be equipped with immune magnetic microsphere.With Fe
3O
4Magnetic and the polymerization single polymerization monomer suspending liquid suspended dispersed in water dispersant that contains functional group reagent, the polymerization by suspending liquid at last directly obtains the immune magnetic microsphere that the surface contains functional group.The immune magnetic microsphere better performances that this method is synthetic, but the content of function monomer is restricted (usually less than 10%), and most of functional group is covered by microballoon inside, only has a spot of functional group to stay the surface, further can cause coupling efficiency low in the binding immunoassay aglucon.Therefore, the application in field of immunology is very limited.
Summary of the invention
The objective of the invention is to overcome that there is a small amount of remanent magnetism in existing immune magnetic microsphere, the surface functional group mass contg is few and its complicated process of preparation, equipment requirements height, defective that productive rate is low, thereby provide that a kind of specific saturation magnetization height, no remanent magnetism, surface functional group are abundant, immune aglucon coupling efficiency height and preparation technology is simple, productive rate is high immune magnetic microsphere, and its production and use.
The objective of the invention is to realize by the following technical solutions:
The invention provides a kind of immune magnetic microsphere, comprise an inorganic magnetic carrier, with the macromolecule shell that is coated on outside it, it is characterized in that, described macromolecule is one or more polymer of monomers that are selected from methyl methacrylate, methyl acrylate, hydroxyethyl methylacrylate, the vinyl acetate, and the alkoxy on the ester group is replaced by amino.
Described inorganic magnetic carrier is Fe
3O
4
The invention provides a kind of preparation method of above-mentioned immune magnetic microsphere, comprise the steps:
1) use conventional chemical coprecipitation to prepare the Fe that oleic acid coats
3O
4Magnetic fluid:
In nitrogen N
2Under the protection, in 70～90 ℃, with ammoniacal liquor or NaHCO
3It is 1: 1.5～2 the iron protochloride and the aqueous solution of ferric trichloride that solution adds mol ratio, and drips oleic acid, separates with magnet after 30 minutes, and use washed with de-ionized water, obtains the Fe of oleic acid coating
3O
4Magnetic fluid;
2) emulsion-suspension polymerization magnetic polymer microsphere:
The Fe that the oleic acid that step 1) is obtained coats
3O
4Magnetic fluid is dispersed in polymer monomer, crosslinking chemical and the initiating agent, forms oil phase;
Wherein, the weight portion of magnetic fluid, polymerization single polymerization monomer, crosslinking chemical, initiating agent is:
Magnetic fluid 0.5～50
Polymerization single polymerization monomer 1～98
Crosslinking chemical 0.2～40
Initiating agent 0.1～10
Described polymerization single polymerization monomer is selected from one or more in methyl methacrylate, methyl acrylate, the hydroxyethyl methylacrylate;
Described crosslinking chemical is divinylbenzene (hereinafter to be referred as DVB) or methacrylic acid glycol ester (hereinafter to be referred as EGDMA);
Described initiating agent is benzoyl peroxide (hereinafter to be referred as BPO) or azo isobutyronitrile (hereinafter to be referred as AIBN);
5～30 weight account polyethylene alcohol are formed water in 80 ℃ of deionized waters that are dissolved in 1000 weight portions;
Under nitrogen protection, after above-mentioned oil phase and water mixing,, stirred 5～90 minutes at 40～60 ℃ earlier with the rotating speed stirring of 300～1800rpm, stirred 1～12 hour at 60～90 ℃ then; Cooling through magnetic resolution, washing, obtains magnetic polymer microsphere;
3) ammonolysis reaction is introduced functional group at microsphere surface:
With step 2) magnetic polymer microsphere, the ammonia that make separates reagent and N, after dinethylformamide (hereinafter to be referred as DMF) mixes with 1: 1～100: 10～500 (mass ratio) ratio, stirred 10～24 hours at 90～120 ℃, cooling, through magnetic resolution, washing, obtain immune magnetic microsphere of the present invention;
It is hydrazine hydrate, ethylenediamine or hexane diamine that described ammonia is separated reagent.
The invention provides of the application of described immune magnetic microsphere in field of immunology.Immune magnetic microsphere provided by the present invention can be earlier at the specific immune aglucon of its surperficial coupling, as albumen, antibody, antigen, agglutinin etc., these immune aglucons can further be discerned corresponding antibody, antigen, biotin etc. in reaction medium then, separate or testing goal thereby reach.Or directly utilize the amino on immune magnetic microsphere surface, identification can with the antibody of amino reaction, antigen, biotin etc.
The invention provides a kind of method of using above-mentioned immune magnetic microsphere coupling immunity aglucon, comprise the steps:
1) activation of immune magnetic microsphere: the immune magnetic microsphere that surface of the present invention is contained primary amine group immerses in excessive 0.2～50v% (volume by volume concentration) glutaraldehyde solution, 30 ℃ of reactions 6～12 hours, through magnetic resolution, washing, obtain the immune magnetic microsphere that aldehyde radical is contained on the surface;
2) coupling immunity aglucon:
The magnetic microsphere that contains aldehyde radical that step 1) is obtained and the solution of immune aglucon mix, and react in 30 ℃ shaking table 2～6 hours, through magnetic resolution, fully wash with phosphate buffer solution, obtain the immune magnetic microsphere of surperficial coupling immunity training base.
Described immune aglucon is albumin A, Protein G or antibody, antigen, agglutinin.
Compare with the immune magnetic microsphere of prior art, the advantage of immune magnetic microsphere provided by the invention is:
1) particle diameter of microballoon so this microballoon has bigger specific surface area, is convenient to the more function aglucon of coupling between 0.5 to 8 micron; Magnetic content height has very strong magnetic responsiveness, can realize the quick separation under the conventional magnetic field; And this size is suitable with cell, more meets the requirement of isolated cell;
2) introduce amino by ammonolysis reaction at microsphere surface, can not make that functional group is coated to inner face, thereby the microsphere surface functional group is abundant, immune aglucon coupling efficiency height;
3) this microballoon has the chemical stability and the excellent biological compatibility of height, can be used for directly being purified into highly purified antibody from material liquid (as ascites, antiserum), has a good application prospect in fields such as immune detection, antibody purification, cell separation;
4) preparation technology of this microballoon is simple, and productive rate is higher.
Embodiment
Below by embodiment technical scheme of the present invention is described further:
Embodiment 1, preparation immune magnetic microsphere I of the present invention
Use conventional chemical coprecipitation to prepare the Fe that oleic acid coats
3O
4Magnetic fluid: in 2 liters of stirring reactors that fill the 500ml deionized water, add 0.086mol iron protochloride (FeCl
24H
2O) and 0.173mol iron chloride (FeCl
36H
2O), in nitrogen N
2Protection is warming up to 90 ℃ down, and impouring contains 0.956mol NH
3H
2The O aqueous solution, and drip the about 15ml of oleic acid, continue constant temperature 30min, after separating with magnet, clean repeatedly through deionized water, obtain the Fe that the crumby oleic acid of black coats
3O
4Magnetic fluid.The about 30g of this magnetic fluid gross weight wherein contains Fe
3O
4About 10g observes Fe under transmission electron microscope
3O
4Particle is bordering on sphere, has superparamagnetism, and mean grain size is 8nm.
Emulsion-suspension polymerization magnetic polymer microsphere: with the Fe of the above-mentioned oleic acid coating of 30.0g
3O
4Magnetic fluid is dispersed in 95g methyl acrylate, 5g divinylbenzene (DVB) and the 5g benzoyl peroxide (BPO), forms oil phase; In 2 liters of cylindrical stirring reactors that condenser and vertical flow-stopping plate be housed, add the 1000ml deionized water, 25 gram polyvinyl alcohol (PVA) (PVA-1788) stir in 80 ℃ of constant temperature PVA are dissolved fully, form water; After above-mentioned oil phase and water mixing, under nitrogen protection,, stirred 30 minutes at 50 ℃ with the stirring rate of 1000rpm, continue to stir 1 hour at 60 ℃ then, be warmed up to 80 ℃ of reactions 2 hours at last; Cooling through magnetic resolution, is used hot wash, obtains magnetic polymer microsphere; This magnetic polymer microsphere has higher magnetic responsiveness, and specific saturation magnetization reaches 14emug
-1, no remanent magnetism, size distribution is at 1～8 μ m.
Ammonolysis reaction is introduced functional group at microsphere surface: with above-mentioned magnetic polyacrylic acid methyl esters (PMA) microballoon 3g, ethylenediamine 50g and solvent N, after dinethylformamide (DMF) 50g mixes, add and be equipped with in three mouthfuls of round-bottomed flasks of 250ml of thermometer, mechanical stirrer and reflux condensing tube, stirred the methoxyl quilt-HNCH on the polymethyl acrylate ester group 20 hours at 90 ℃
2CH
2NH
2Replace; After the cooling, magnetic resolution is used deionized water wash, obtains immune magnetic microsphere I of the present invention, and primary amine group is contained on its surface.
Embodiment 2, preparation immune magnetic microsphere II of the present invention
Use conventional chemical coprecipitation to prepare the Fe that oleic acid coats
3O
4Magnetic fluid: in 2 liters of stirring reactors that fill the 700ml deionized water, add 0.17mol iron protochloride (FeCl
24H
2O) and 0.34mol iron chloride (FeCl
36H
2O), in nitrogen N
2Protection is warming up to 70 ℃, the NaHCO of impouring 56ml25% down
3Aqueous solution, and drip the about 20ml of oleic acid, continue constant temperature until the clarification of upper strata liquid, after separating with magnet, clean repeatedly through deionized water, obtain the Fe that the crumby oleic acid of black coats
3O
4Magnetic fluid.The about 60g of this magnetic fluid gross weight wherein contains Fe
3O
4About 20g observes Fe under transmission electron microscope
3O
4Particle is bordering on sphere, has superparamagnetism, and mean grain size is 12nm.
Emulsion-suspension polymerization magnetic polymer microsphere: with the Fe of the above-mentioned oleic acid coating of 40.0g
3O
4Magnetic fluid is dispersed in 98g methyl methacrylate, 40g divinylbenzene (DVB) and the 10g benzoyl peroxide (BPO), forms oil phase; In 2 liters of cylindrical stirring reactors that condenser and vertical flow-stopping plate be housed, add the 1000ml deionized water, 30 gram polyvinyl alcohol (PVA) (PVA-1788) and 0.1 gram methylene blue (polymerization inhibitor) stir in 80 ℃ of constant temperature PVA are dissolved fully, the formation water; After above-mentioned oil phase and water mixing, under nitrogen protection,, stirred 90 minutes at 40 ℃ with the stirring rate of 300rpm, continue to stir 12 hours at 90 ℃ then; Cooling through magnetic resolution, is used hot wash, obtains magnetic polymer microsphere; This magnetic polymer microsphere has higher magnetic responsiveness, and specific saturation magnetization reaches 17emug
-1, no remanent magnetism, size distribution is at 1～8 μ m.
Ammonolysis reaction is introduced functional group at microsphere surface: with above-mentioned magnetic polymethyl methacrylate microsphere 2g, hexane diamine 2g and solvent N, after dinethylformamide (DMF) 20g mixes, add and be equipped with in three mouthfuls of round-bottomed flasks of 250ml of thermometer, mechanical stirrer and reflux condensing tube, stirred the methoxyl quilt-HN (CH on the polymethylmethacrylate ester group 24 hours at 110 ℃
2)
6NH
2Replace; After the cooling, magnetic resolution is used deionized water wash, obtains immune magnetic microsphere II of the present invention, and primary amine group is contained on its surface.
Embodiment 3, preparation immune magnetic microsphere III of the present invention
Use conventional chemical coprecipitation to prepare the Fe that oleic acid coats
3O
4Magnetic fluid: in 2 liters of stirring reactors that fill the 600ml deionized water, add 0.20mol iron protochloride (FeCl
24H
2O) and 0.40mol iron chloride (FeCl
36H
2O), in nitrogen N
2Protection is warming up to 80 ℃ down, impouring 65ml water containing ammonia, and drip the about 35ml of oleic acid, and continue constant temperature until the clarification of upper strata liquid, after separating with magnet, clean repeatedly through deionized water, obtain the Fe that the crumby oleic acid of black coats
3O
4Magnetic fluid.The about 75g of this magnetic fluid gross weight wherein contains Fe
3O
4About 24g observes Fe under transmission electron microscope
3O
4Particle is bordering on sphere, has superparamagnetism, and mean grain size is 18nm.
Emulsion-suspension polymerization magnetic polymer microsphere: with the Fe of the above-mentioned oleic acid coating of 0.5g
3O
4Magnetic fluid is dispersed in 1g hydroxyethyl methylacrylate, 0.2g methacrylic acid glycol ester (EGDMA) and the 0.1g azo isobutyronitrile (AIBN), forms oil phase; In 2 liters of cylindrical stirring reactors that condenser and vertical flow-stopping plate be housed, add the 1000ml deionized water, 5 gram polyvinyl alcohol (PVA) (PVA-1788) stir in 80 ℃ of constant temperature PVA are dissolved fully, form water; After above-mentioned oil phase and water mixing, under nitrogen protection,, stirred 5 minutes at 60 ℃ with the stirring rate of 1800rpm, continue to stir 6 hours at 80 ℃ then; Cooling through magnetic resolution, is used hot wash, obtains magnetic polymer microsphere; This magnetic polymer microsphere has higher magnetic responsiveness, and specific saturation magnetization reaches 14emug
-1, no remanent magnetism, size distribution is at 1～8 μ m.
Ammonolysis reaction is introduced functional group at microsphere surface: with above-mentioned magnetic polymethylacrylic acid glycol ester microballoon 2g, hydrazine hydrate 200g and solvent N, after dinethylformamide (DMF) 1000g mixes, add and be equipped with in three mouthfuls of round-bottomed flasks of 250ml of thermometer, mechanical stirrer and reflux condensing tube, stirred the glycol ester oxygen base quilt-HNNH on the polymethylacrylic acid glycol ester ester group 10 hours at 120 ℃
2H
2O replaces; After the cooling, magnetic resolution is used deionized water wash, obtains immune magnetic microsphere III of the present invention, and primary amine group is contained on its surface.
Embodiment 4, use immune magnetic microsphere I coupling immunity of the present invention aglucon
The activation of immune magnetic microsphere: the immune magnetic microsphere I that primary amine group is contained on the surface that 1.0g embodiment 1 is obtained immerses in 5v% (volume by volume concentration) glutaraldehyde solution of 50ml, in 30 ℃ of oscillating reactionss 6 hours in shaking table, oscillation rate is 200rpm, through magnetic resolution, fully wash with deionized water, obtain the immune magnetic microsphere that aldehyde radical is contained on the surface;
Coupling immunity aglucon: with this immune magnetic carrier microballoons 5mg that contains aldehyde radical in the centrifuge tube of 1.5ml, the concentration that adds 1ml is the albumin A solution of 1mg/ml, oscillating reactions is 3 hours in 30 ℃ shaking table, after coupling protein A finishes, with concentration is the bovine serum albumin(BSA) BSA shutoff 0.5 hour of 10mg/ml, through magnetic resolution, fully wash with phosphate buffer solution, obtain the immune magnetic microsphere of surperficial coupling protein A.
Embodiment 5, use immune magnetic microsphere II coupling immunity of the present invention aglucon
The activation of immune magnetic microsphere: the immune magnetic microsphere II that primary amine group is contained on the surface that 3.0g embodiment 2 is obtained immerses in 50v% (volume by volume concentration) glutaraldehyde solution of 30ml, in 30 ℃ of oscillating reactionss 12 hours in shaking table, oscillation rate is 200rpm, through magnetic resolution, fully wash with deionized water, obtain the immune magnetic microsphere that aldehyde radical is contained on the surface;
Coupling immunity aglucon: with this immune magnetic microsphere 100mg that contains aldehyde radical in the Erlenmeyer flask of 50ml, the concentration that adds 20ml is the Protein G solution of 5mg/ml, oscillating reactions is 2 hours in 30 ℃ shaking table, after coupling protein G finishes, with concentration is the bovine serum albumin(BSA) BSA shutoff 0.5 hour of 10mg/ml, through magnetic resolution, fully wash with phosphate buffer solution, obtain the immune magnetic microsphere of surperficial coupling protein G.
Embodiment 6, use immune magnetic microsphere III coupling immunity of the present invention aglucon
The activation of immune magnetic microsphere: the immune magnetic microsphere III that primary amine group is contained on the surface that 3.0g embodiment 3 is obtained immerses in 0.2v% (volume by volume concentration) glutaraldehyde solution of 1000ml, in 30 ℃ of oscillating reactionss 10 hours in shaking table, oscillation rate is 200rpm, through magnetic resolution, fully wash with deionized water, obtain the immune magnetic microsphere that aldehyde radical is contained on the surface;
Coupling immunity aglucon: with this immune magnetic microsphere 100mg that contains aldehyde radical in the Erlenmeyer flask of 50ml, the concentration that adds 20ml is the mouse IgG2a antibody-solutions of 5mg/ml, oscillating reactions is 6 hours in 30 ℃ shaking table, after coupling IgG2a antibody finishes, with concentration is the bovine serum albumin(BSA) BSA shutoff 0.5 hour of 10mg/ml, through magnetic resolution, fully wash with phosphate buffer solution, obtain the immune magnetic microsphere of surperficial coupling IgG2a antibody.
Claims (9)
1, a kind of immune magnetic microsphere, comprise an inorganic magnetic carrier, with the macromolecule shell that is coated on outside it, it is characterized in that, described macromolecule is one or more polymer of monomers that are selected from methyl methacrylate, methyl acrylate, hydroxyethyl methylacrylate, the vinyl acetate, and the alkoxy on the ester group is replaced by amino.
2, immune magnetic microsphere as claimed in claim 1 is characterized in that, described inorganic magnetic carrier is Fe
3O
4
3, the preparation method of the described immune magnetic microsphere of a kind of claim 1 comprises the steps:
1) use conventional chemical coprecipitation to prepare the Fe that oleic acid coats
3O
4Magnetic fluid;
2) emulsion-suspension polymerization magnetic polymer microsphere:
The Fe that the oleic acid that step 1) is obtained coats
3O
4Magnetic fluid is dispersed in polymer monomer, crosslinking chemical and the initiating agent, forms oil phase;
Wherein, the weight portion of magnetic fluid, polymerization single polymerization monomer, crosslinking chemical, initiating agent is:
Magnetic fluid 0.5～50
Polymerization single polymerization monomer 1～98
Crosslinking chemical 0.2～40
Initiating agent 0.1～10
Described polymerization single polymerization monomer is selected from one or more in methyl methacrylate, methyl acrylate, the hydroxyethyl methylacrylate;
5～30 weight account polyethylene alcohol are formed water in 80 ℃ of deionized waters that are dissolved in 1000 weight portions;
Under nitrogen protection, after above-mentioned oil phase and water mixing,, stirred 5～90 minutes at 40～60 ℃ earlier with the rotating speed stirring of 300～1800rpm, stirred 1～12 hour at 60～90 ℃ then; Cooling through magnetic resolution, washing, obtains magnetic polymer microsphere;
3) ammonolysis reaction is introduced functional group at microsphere surface:
With step 2) magnetic polymer microsphere, the ammonia that make separates reagent and N, dinethylformamide stirred 10～24 hours cooling after mixing with 1: 1～100: 10～500 mass ratio at 90～120 ℃, through magnetic resolution, washing, obtain immune magnetic microsphere of the present invention.
4, the preparation method of immune magnetic microsphere as claimed in claim 3 is characterized in that, described step 2) in crosslinking chemical be divinylbenzene or methacrylic acid glycol ester.
5, the preparation method of immune magnetic microsphere as claimed in claim 3 is characterized in that, described step 2) in initiating agent be benzoyl peroxide or azo isobutyronitrile.
6, the preparation method of immune magnetic microsphere as claimed in claim 3 is characterized in that, it is hydrazine hydrate, ethylenediamine or hexane diamine that the ammonia in the described step 3) is separated reagent.
7, the described immune magnetic microsphere of a kind of claim 1 is in the application of field of immunology.
8, a kind of method of using the described immune magnetic microsphere coupling immunity of claim 1 aglucon comprises the steps:
1) activation of immune magnetic microsphere: the described immune magnetic microsphere of claim 1 is immersed in excessive 0.2～50v% glutaraldehyde solution,,, obtain the immune magnetic microsphere that aldehyde radical is contained on the surface through magnetic resolution, washing 30 ℃ of reactions 6～12 hours;
2) coupling immunity aglucon: the immune magnetic microsphere that contains aldehyde radical that step 1) is obtained and the solution of immune aglucon mix, in 30 ℃ shaking table, reacted 2～6 hours, through magnetic resolution, fully wash with phosphate buffer solution, obtain the immune magnetic microsphere of surperficial coupling immunity aglucon.
9, the method for immune magnetic microsphere coupling immunity aglucon as claimed in claim 8 is characterized in that described immune aglucon is albumin A, Protein G or antibody, antigen, agglutinin.
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| CN108333343A (en) * | 2017-01-19 | 2018-07-27 | 深圳市新产业生物医学工程股份有限公司 | Immune magnetic compound, preparation method including its antigen capture agent, kit, system and application |
| CN107435039A (en) * | 2017-06-13 | 2017-12-05 | 安徽安龙基因医学检验所有限公司 | A kind of preparation method and storage method of the immunomagnetic beads for sorting leucocyte |
| CN107490681A (en) * | 2017-09-29 | 2017-12-19 | 安徽安龙基因科技有限公司 | A kind of preparation method of EpCAM antibody immune magnetic beads |
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