CN102115746B - Preparation method of monodisperse magnetic human ferritin - Google Patents
Preparation method of monodisperse magnetic human ferritin Download PDFInfo
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Abstract
The invention relates to a preparation method of a monodisperse magnetic human ferritin, which comprises the following steps: forming magnetic nanoparticles inside a recombinant human ferritin, which is directly used as a template, by a one-step bionic synthesis method, and separating and purifying to obtain the monodisperse magnetic human ferritin which has no magnetic interaction. The magnetic human ferritin prepared by the method provided by the invention has a complete recombinant human ferritin shell and magnetic nanoparticle core; the core component is Fe3O4 or gamma-Fe2O3, and usually has the characteristics of uniform dimension, similar shape and favorable dispersity; and the average diameter of the cores can be controlled between 1 nanometer and 10 nanometers, and is dependent on the number of iron atoms added in the synthesis process. The magnetic human ferritin prepared by the method is monodisperse and has no magnetic interaction, thereby solving the common problem of aggregation in the magnetic nanoparticles; and the magnetic human ferritin can stably exist for a long time, and has wide application prospects and market prospects in the fields of biomedicine, electronics and environment.
Description
Technical field
The invention belongs to the biomimetic synthesis technology field of magnetic Nano material, relate to particularly a kind of preparation method of magnetic human ferritin of monodispersity.
Background technology
Superparamagnetic magnetite (Fe
3O
4) or maghemite (γ-Fe
2O
3) due to its good magnetic property and nanometer size effect, be widely used in electronics (high-density magnetic storage), chemical industry (magnetic fluid, catalysis, coating), environmentalism (environment remediation) and fields such as biomedical (magnetic target medicine, magnetic resonance contrast agent, cell marking are separated, DNA separates, medical diagnosis on disease).But in the preparation field of nano magnetic particle, how to synthesize that uniform particle diameter, shape are identical, the nano magnetic particle of good dispersity and monodispersity is the focus of research always.
Ferritin is natural iron ore albumen, it is distributed widely in microorganism, plant, animal and human body, bring into play the toxicity of removing ferrous ion and the function of storing iron in body, bringing into play vital effect in the biomineralization process of the iron metabolism in body and iron.Native ferritin can form spherical cage shape protein shell structure due to the height self-assembly of protein protomer, and its outside diameter is about 12nm, and interior diameter is about 8nm, size height homogeneous.An iron core is contained in the protein shell inside of each cage modle, and the iron core of native ferritin is about 6-8nm, and its composition is anti-ferromagnetic hydrous iron oxide.Thereby the iron core of native ferritin discharges under the condition of acidic conditions and reductive agent existence and forms the ghost ferritin, and still keep the cagelike structure of its homogeneous due to the ghost ferritin, so can be as the bionical synthetic template of nano material, synthetic nano material has usually that size homogeneous, shape are similar, good dispersity and have the natural advantages such as protein shell.
Armco magnetic iron albumen is a kind of bionical synthetic materials, is a kind of ferritin with magnetite or maghemite kernel.Synthesizing normally take native ferritin as raw material of traditional Armco magnetic iron albumen, at first under the condition of acidic conditions and reductive agent existence, original hydrous iron oxide iron core is removed, form the ghost ferritin, and then the change by electrochemical conditions is at inner magnetite or the maghemite particle (U.S.patent 5491219) of forming of protein shell.But the route of this traditional synthesizing magnetic ferritin usually need to be removed the iron karyomorphism and become this step of ghost ferritin, and this step easily causes the damage of protein shell because complete under acidic conditions; Loaded down with trivial details due to this process in addition, the loss amount of albumen also can increase.And forefathers' research shows too, and the synthetic Armco magnetic iron albumen of this traditional method is easily assembled, and has magnetic interaction (Moskowitz et al., 1997).This gathering not only can influencing magnetic particles magnetic property, but also can affect its application in biomedicine.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of monodisperse magnetic human ferritin.
For achieving the above object, the preparation method of monodisperse magnetic human ferritin provided by the invention, take recombinant human iron albumen as template, by bionical synthetic, inside at recombinant human iron albumen forms magnetic nanoparticle, obtain monodisperse magnetic human ferritin through separation and purification, key step is as follows:
1) take recombinant human iron albumen as template, the H subunit of people's ferritin and the full-length cDNA of L subunit are cloned respectively and be building up on plasmid;
The recombinant plasmid that 2) will contain people's ferritin H subunit and L subunit transforms respectively or cotransformation bacterium Rosetta (DE3) pLysS, adds IPTG (isopropyl-β-D-thiogalactoside(IPTG)) to activate T7 promotor, abduction delivering;
3) carry out ultrasonication after expression finishes and discharge albumen;
4) albumen is separated and purifying;
5) ferrous salt and oxygenant are added in the solution of recombinant human iron albumen and react, controlling pH value is 7～11, and the control temperature is 25～80 ℃, forms ferromagnetic nano particle in the recombinant human iron active site of protein; Between 10～200, finally the iron atom number that adds of each protein molecular can be between 100～5000 for the ratio of the ferrous atomicity that adds and protein molecular number at every turn for the concentration of ferrous salt; The concentration of oxygenant is for add H at every turn
2O
2The ratio of molecule number and the atomicity that adds ferrous ion be 2: 1 or 3: 1; Protein concentration＞0.25mg/ml;
6) exclusion chromatography separates, and obtains monodisperse magnetic people ferritin particle after centrifugal and molecular sieve purification.
In preparation method of the present invention, recombinant human iron albumen comprises mutant or the fusion rotein of the L chain of the mutant of H chain of assembly, recombinant human iron albumen of the H chain of L chain, recombinant human iron albumen of H chain, the recombinant human iron albumen of recombinant human iron albumen and L chain or fusion rotein and recombinant human iron albumen.
In preparation method of the present invention, after step 1, encoding sequence is checked order guarantee to have correct DNA sequence dna.
In preparation method of the present invention, in step 2, be when bacterial reproduction is 0.7 to the OD value, then add IPTG to activate the T7 promotor, at 37 ℃ of abduction deliverings.
Preparation method of the present invention wherein, in step 3, is that bacterium is resuspended in and carries out ultrasonication in Tris-HCl buffered soln and discharge albumen.
Preparation method of the present invention and, in step 4, adopt chromatography method, ammonium sulfate precipitation, ion-exchange or molecular exclusion chromatography protein isolate.
In preparation method of the present invention, in step 5, ferrous salt and oxygenant are water-soluble ferrous salt: ferrous sulfate, ferrous ammonium sulphate or iron protochloride; Oxygenant is hydrogen peroxide.
In preparation method of the present invention, in step 5, controlling pH is 8～8.5; Controlling temperature is 37 ℃ or 65 ℃.
In preparation method of the present invention, in step 6, exclusion chromatography medium used is Sepharose 4B or superose 6, and the buffered soln of use is 0.025M Tris-HCl (pH 7.25) buffered soln of pH=7.25, and flow velocity is 0.25ml/min.
In preparation method of the present invention, the magnetic nanoparticle that forms in the inside of recombinant human iron albumen comprises magnetite or maghemite.
Compare with traditional Armco magnetic iron albumen and other magnetic nanoparticle preparation method, the present invention has the following advantages:
1) by the standby magnetic human ferritin of this legal system directly take the recombinant human iron albumen of iron-free core as template, only need to synthesize once going on foot in synthetic, omitted a step that needs to remove iron core in the traditional method, thereby can avoid loss of proteins or damage in numerous and diverse step, also meet the needs of commercial production scale.
2) have complete recombinant human iron protein shell by the standby magnetic human ferritin of this legal system, because the recombinant human iron protein shell is produced by gene engineering method, can obtain in a large number, and easilier transform and modify by gene engineering method.As can merge pharmaceutical polypeptide on the subunit of ferritin, thereby can magnetic human ferritin become the multifunction magnetic particle of functions such as integrating medicine carrying, target and mr development.
3) the people's ferritin shell that possesses by the standby magnetic human ferritin of this legal system is the H chain of the recombinant human iron albumen of people's ferritin, the assembly of the L chain of recombinant human iron albumen or the H chain of recombinant human iron albumen and L chain, they have the protein sequence similar to people's ferritin, thereby probably can avoid due to species difference immunogenicity that human body is caused, thereby in the biomedicines such as the mr development of human body, magnetic target agent, cell marking, purposes widely may be arranged.
4) be monodispersed and without magnetic interaction by the standby magnetic human ferritin of this legal system, thereby can avoid the normal rendezvous problem that exists of nano magnetic particle, chronically stable existence and have larger specific surface area.
5) the people's ferritin shell by the standby magnetic human ferritin of this legal system can be to keep the integrity of protein structure in 4～11 at pH, and high temperature that can anti-70～80 ℃.Due to the polymolecularity of this magnetic human ferritin, so can carry out easily filtration sterilization, these characteristics are very beneficial for storage and the transportation of magnetic human ferritin in addition.
Description of drawings
Fig. 1 is transmission electron microscope (TEM) the negative staining photo of the magnetic human ferritin of the monodispersity for preparing of the present invention.
Fig. 2 a-Fig. 2 d is transmission electron microscope (TEM) photo by the magnetic human ferritin of the prepared monodispersity of embodiment 1-4.
Fig. 3 is selected area electron diffraction (SAED) figure of the magnetic human ferritin of the monodispersity for preparing of the present invention.
Fig. 4 a-Fig. 4 b is that the SIRM of magnetic human ferritin when 5K of the monodispersity for preparing of the present invention obtains that Wohlfarth-Cisowski that curve and SIRM demagnetizing curve set up detects and Henkel schemes.
Embodiment
The protein shell that the prepared Armco magnetic iron albumen of the present invention is directly assembled take recombinant expressed people's ferritin subunit is as template, the characteristics of this recombinant human iron albumen are there is no natural hydrous iron oxide iron core, thereby do not need to carry out traditional this step of removal iron core, directly can be used for the magnetic nanoparticle of bionical synthetic uniform particle diameter, good biocompatibility.This Armco magnetic iron albumen take people's ferritin as protein shell probably can be avoided the immunogenicity that species difference was caused due to albumen in addition, thereby makes this Armco magnetic iron albumen that prior purposes be arranged in human medical.The Armco magnetic iron albumen that the method makes also comprises the purifying process after synthetic, makes the magnetic human ferritin of preparation have monodispersity and without the characteristics of magnetic interaction.
Magnetic human ferritin according to method preparation of the present invention has complete recombinant human iron protein shell and magnetic nanoparticle core, the diameter of core can be in 1 nanometer between 10 nanometers, depend on added iron atom number in building-up process, have dispersibility and solvability in water and polar solvent.The composition of core is Fe
3O
4Perhaps γ-Fe
2O
3
The method of the magnetic human ferritin of preparation monodispersity provided by the invention, comprise take recombinant human iron albumen as template, by bionical synthetic method, form magnetic nanoparticle in the inside of recombinant human iron albumen, then through separation and purification resulting single disperse and without the magnetic human ferritin of magnetic interaction.
To be that two-step approach preparation is single disperse and without the method for the magnetic human ferritin of magnetic interaction, its main contents have following 3 points in the present invention:
1) take recombinant human iron albumen as template.Wherein recombinant human iron albumen comprises the H chain of recombinant human iron albumen, the L chain of recombinant human iron albumen, the H chain of recombinant human iron albumen and the assembly of L chain, mutant or the fusion rotein of the H chain of recombinant human iron albumen, mutant or the fusion rotein of the L chain of recombinant human iron albumen.The recombinant technology of use genetically engineered field routine just can build recombinant human iron albumen.In this course, use take PCR as the method on basis the H subunit of people's ferritin and the full-length cDNA of L subunit are cloned respectively and be building up on plasmid, and encoding sequence is checked order guarantee to have correct DNA sequence dna.The recombinant plasmid that will contain again people's ferritin H subunit and L subunit transforms respectively or cotransformation bacterium Rosetta (DE3) pLysS.When bacterial reproduction is 0.7 (650nm) to suitable concn such as OD value, add 1mM IPTG to activate the T7 promotor, at 37 ℃ of abduction deliverings.After expression finishes, bacterium is resuspended in and carries out ultrasonication release albumen in Tris-HCl buffered soln.Then albumen is separated and purifying, as adopt the protein isolate from supernatant liquor such as suitable chromatography method or additive method such as ammonium sulfate precipitation, ion-exchange, molecular exclusion chromatography.Transmission electron microscope results shows that these recombinant human iron albumen can the glomerate cagelike structure of self-assembly shape.Wherein the cagelike structure of recombinant protein self-assembly formation is the ghost ferritin, there is no obvious iron core.Thereby can be directly used in the synthetic template of Armco magnetic iron albumen.
2) oxygenant with ferrous salt and proper ratio reacts in the solution that adds recombinant human iron albumen, by controlling reaction conditions, does not destroy the cagelike structure of protein shell, forms ferromagnetic nano particle in the recombinant human iron active site of protein.Water-soluble ferrous salt of the present invention mainly comprises the water-soluble ferrous salts such as ferrous sulfate, ferrous ammonium sulphate, iron protochloride, and the oxygenant that adopts is hydrogen peroxide (H
2O
2).Wherein comprise control pH value by controlling reaction conditions, control temperature, control protein concentration, control the concentration that adds water-soluble ferrous salt, control the concentration that adds oxygenant.Wherein controlling the pH value can select between 7～11, and preferred pH is 8～8.5.Wherein controlling temperature can select between 25～80 ℃, wherein preferred 37 ℃ and 65 ℃.Wherein control protein concentration and refer to that protein concentration can select between＞0.25mg/ml.Wherein control ratio that the concentration add water-soluble ferrous salt refers to add ferrous atomicity after reaction soln and protein molecular number at every turn between 10～200, finally the iron atom number that adds of each protein molecular can be between 100～5000.Wherein control adds the concentration of oxygenant to refer to add H at every turn
2O
2The ratio of molecule number and the atomicity that adds ferrous ion be 2: 1 or 3: 1.This suitable ferrous salt and hydrogen peroxide can form in the recombinant human iron active site of protein Fe of homogeneous grain diameter at suitable ratio and suitable pH and temperature
3O
4Perhaps γ-Fe
2O
3Nano particle.
3) can obtain monodispersed after the magnetic human ferritin after synthesizing separates by further exclusion chromatography and without the magnetic human ferritin particle of magnetic interaction.The medium used of exclusion chromatography wherein can be Sepharose 6B or superose 6, and the buffered soln of use is 0.025MTris-HCl (pH 7.25) buffered soln, and flow velocity is 0.25ml/min.The monodisperse magnetic ferritin that obtains by separation is by the good dispersiveness of transmission electron microscope detection display, and the Wohlfarth-Cisowski of the remanent magnetism curve by the low temperature magnetics detects and Henkel figure detection is nano magnetic particle without magnetic interaction.
Explain below in conjunction with drawings and Examples.
Embodiment 1
Configure respectively the ferrous ammonium sulphate 50ml of 25mM, the H of 8.34mM with the water of removing oxygen in the anaerobism glove box
2O
2The NaOH 100ml of 50ml and 50mM uses the sodium chloride solution of the 0.1M that removes oxygen to be diluted to 50ml the restructuring H chain liquor ferri albuminati after purifying, puts in reaction cup.Final protein concentration is at 0.25mg/ml (Tot Prot 24.4nmol, restructuring H catenin molecular weight is 513kD).At first with electric mantle, the protein solution in reaction cup is heated to 65 ℃, add stirrer to guarantee that with the magnetic force rapid stirring solution temperature is even during heating, by the constant pH titration apparatus, the pH value of protein solution is adjusted to 8.5 with the NaOH of 50mM after homo(io)thermism 15min, then adds the ferrous ammonium sulphate (each protein molecular per minute enters 100 iron atoms) of 25mM and the H of 8.34mM according to the speed of 97.6 μ l/min by automatic liquid adding device in protein solution
2O
2, add respectively at last ferrous ammonium sulphate and H
2O
22.245ml finally the iron atom number that on average adds of each protein molecular is 2300 iron atoms.Magnetic human ferritin after synthetic by exclusion chromatography medium Sepharose 6B (pillar that 70cm is long), is obtained the magnetic human ferritin of monodispersity at last.Fig. 1 is the negative staining photo of transmission electron microscope (TEM) of the Armco magnetic iron albumen of gained, and this magnetic human ferritin by complete recombinant human iron protein encapsulation, shows well dispersed as shown in Figure 1.Fig. 2 a is the transmission electron microscope photo of gained magnetic human ferritin core, by Fig. 2 a as can be known the median size of core be 3.9nm.Fig. 3 is the selected area electron diffraction figure of magnetic human ferritin, and the composition of magnetic human ferritin core is magnetite as shown in Figure 3.Fig. 4 is that the SIRM of this magnetic human ferritin when 5K obtains that Wohlfarth-Cisowski that curve and SIRM demagnetizing curve set up detects and Henkel schemes, there is not magnetic interaction in the magnetic human ferritin that obtains by separation as shown in Figure 4, is magnetite at the 200mT composition that shows magnetic human ferritin core that just can reach capacity.
Embodiment 2
Use the sodium chloride solution of the 0.1M that removes oxygen to be diluted to 50ml the restructuring H chain liquor ferri albuminati after purifying, put in reaction cup.Final protein concentration is at 1mg/ml, at first with electric mantle, the protein solution in reaction cup is heated to 65 ℃, add stirrer to guarantee that with the magnetic force rapid stirring solution temperature is even during heating, by the constant pH titration apparatus, the pH value of protein solution is adjusted to 8.5 with the NaOH of 50mM after homo(io)thermism 15min, then adds the ferrous ammonium sulphate (each protein molecular per minute enters 100 iron atoms) of 25mM and the H of 8.34mM according to the speed of 390.4 μ l/min by automatic liquid adding device in protein solution
2O
2, add respectively at last ferrous ammonium sulphate and H
2O
28.98ml finally the iron atom number that on average adds of each protein molecular is 2300 iron atoms.All the other operations are all with embodiment 1.Fig. 2 b is the transmission electron microscope photo of the magnetic human ferritin core of gained, by Fig. 2 b as can be known the median size of core be 4.2nm.
Embodiment 3
Use the sodium chloride solution of the 0.1M that removes oxygen to be diluted to 50ml the restructuring H chain liquor ferri albuminati after purifying, put in reaction cup.Final protein concentration is at 0.5mg/ml, at first with electric mantle, the protein solution in reaction cup is heated to 37 ℃, add stirrer to guarantee that with the magnetic force rapid stirring solution temperature is even during heating, by the constant pH titration apparatus, the pH value of protein solution is adjusted to 8.5 with the NaOH of 50mM after homo(io)thermism 15min, then adds the ferrous ammonium sulphate (each protein molecular per minute enters 100 iron atoms) of 25mM and the H of 8.34mM according to the speed of 195.2 μ l/min by automatic liquid adding device in protein solution
2O
2, add respectively at last ferrous ammonium sulphate and H
2O
24.49ml finally the iron atom number that on average adds of each protein molecular is 2300 iron atoms.All the other operations are all with embodiment 1.Fig. 2 c is the transmission electron microscope photo of the magnetic human ferritin core of gained, by Fig. 2 c as can be known the median size of core be 4nm.
Embodiment 4
Use the sodium chloride solution of the 0.1M that removes oxygen to be diluted to 50ml the restructuring L chain liquor ferri albuminati after purifying, put in reaction cup.Final protein concentration is at 1mg/ml, at first with electric mantle, the protein solution in reaction cup is heated to 37 ℃, add stirrer to guarantee that with the magnetic force rapid stirring solution temperature is even during heating, by the constant pH titration apparatus, the pH value of protein solution is adjusted to 8.5 with the NaOH of 50nM after homo(io)thermism 15min, then adds the ferrous ammonium sulphate (each protein molecular per minute enters 100 iron atoms) of 25mM and the H of 8.34nM according to the speed of 353.2 μ l/min by automatic liquid adding device in protein solution
2O
2, add respectively at last ferrous ammonium sulphate and H
2O
28.125ml finally the iron atom number that on average adds of each protein molecular is 2300 iron atoms.All the other operations are all with embodiment 1.Fig. 2 d is the transmission electron microscope photo of the magnetic human ferritin core of gained, by Fig. 2 d as can be known the median size of core be 4.5nm.
Claims (9)
1. the preparation method of a monodisperse magnetic human ferritin, take recombinant human iron albumen as template, by bionical synthetic, form magnetic nanoparticle in the inside of recombinant human iron albumen, obtains monodisperse magnetic human ferritin through separation and purification, and key step is as follows:
1) take recombinant human iron albumen as template, the H subunit of people's ferritin and the full-length cDNA of L subunit are cloned respectively and be building up on plasmid;
The recombinant plasmid that 2) will contain people's ferritin H subunit and L subunit transforms respectively or cotransformation bacterium Rosetta (DE3) pLysS, adds isopropyl-β-D-thiogalactoside(IPTG) to activate T7 promotor, abduction delivering;
3) carry out ultrasonication after expression finishes and discharge albumen;
4) albumen is separated and purifying;
5) ferrous salt and oxygenant are added in the solution of recombinant human iron albumen and react, controlling pH value is 7～11, and the control temperature is 25～80 ℃, forms ferromagnetic nano particle in the recombinant human iron active site of protein; Between 10～200, finally the iron atom number that adds of each protein molecular is between 100～5000 for the ratio of the ferrous atomicity that adds and protein molecular number at every turn for the concentration of ferrous salt; The concentration of oxygenant is for add H at every turn
2O
2The ratio of molecule number and the atomicity that adds ferrous ion be 2: 1 or 3: 1; Protein concentration＞0.25mg/ml;
6) exclusion chromatography separates, and obtains monodisperse magnetic people ferritin particle after centrifugal and molecular sieve purification.
2. according to claim 1 preparation method, wherein, step 1) afterwards, encoding sequence is checked order guarantee to have correct DNA sequence dna.
3. according to claim 1 preparation method, wherein, step 2) in, be when bacterial reproduction is 0.7 to the OD value, then add isopropyl-β-D-thiogalactoside(IPTG) to activate the T7 promotor, at 37 ℃ of abduction deliverings.
4. according to claim 1 preparation method, wherein, step 3), be that bacterium is resuspended in and carries out ultrasonication in Tris-HCl buffered soln and discharge albumen.
5. according to claim 1 preparation method, wherein, step 4) in, adopt chromatography method, ammonium sulfate precipitation, ion-exchange or molecular exclusion chromatography protein isolate.
6. according to claim 1 preparation method, wherein, step 5) in, ferrous salt is water-soluble ferrous salt; Oxygenant is hydrogen peroxide.
7. according to claim 1 preparation method, wherein, step 5) in, controlling pH is 8～8.5; Controlling temperature is 37 ℃ or 65 ℃.
8. according to claim 1 preparation method, wherein, step 6) in, exclusion chromatography medium used is Sepharose 6B or superose 6, and the buffered soln of use is the 0.025M Tris-HCl buffered soln of pH=7.25, and flow velocity is 0.25ml/min.
9. according to claim 1 preparation method, wherein, the magnetic nanoparticle that forms in the inside of recombinant human iron albumen comprises magnetite or maghemite.
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| CN103212093B (en) * | 2012-01-19 | 2016-09-28 | 中国科学院地质与地球物理研究所 | A kind of have cell targeted magnetic Nano material and biomedical applications thereof |
| CN102608327A (en) * | 2012-03-01 | 2012-07-25 | 江苏省原子医学研究所 | Trace marking method of ferritin |
| CN109239113B (en) * | 2018-09-30 | 2019-06-14 | 中国科学院地质与地球物理研究所 | The transmission electron microscope sample preparation method of the Armco magnetic iron protein nano particle of bio-mimetic syntheses |
| CN110272500B (en) * | 2019-07-09 | 2020-07-14 | 中国科学院地质与地球物理研究所 | Ferritin nano material for displaying antibody and preparation method and application thereof |
| CN114907576A (en) * | 2021-02-07 | 2022-08-16 | 中国科学院地质与地球物理研究所 | Polymer-coated nano-particles, composite nano-emulsion and macro-emulsion |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5491219A (en) * | 1993-06-11 | 1996-02-13 | Protein Magnetics | Ferritin with ferrimagnetically ordered ferrite core and method technical field |
| CN1659187A (en) * | 2002-05-10 | 2005-08-24 | 新世纪药品有限公司 | Ferritin fusion proteins for use in vaccines and other applications |
| CN201321453Y (en) * | 2008-11-12 | 2009-10-07 | 中国科学院地质与地球物理研究所 | Two-way device for collecting magnetotactic bacteria |
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2009
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5491219A (en) * | 1993-06-11 | 1996-02-13 | Protein Magnetics | Ferritin with ferrimagnetically ordered ferrite core and method technical field |
| CN1659187A (en) * | 2002-05-10 | 2005-08-24 | 新世纪药品有限公司 | Ferritin fusion proteins for use in vaccines and other applications |
| CN201321453Y (en) * | 2008-11-12 | 2009-10-07 | 中国科学院地质与地球物理研究所 | Two-way device for collecting magnetotactic bacteria |
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| Title |
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| D.P.E. Dickson et al."Properties of magnetoferritin：A novel biomegnetic nanoparticle".《Nanostructured Materials》.1997,第9卷(第8期), |
| D.P.E. Dickson et al."Properties of magnetoferritin:A novel biomegnetic nanoparticle".《Nanostructured Materials》.1997,第9卷(第8期), * |
| 胡有生 等."用铁蛋白合成纳米粒子的研究进展".《氨基酸和生物资源》.2003,第25卷(第3期), |
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