CN104762085A - Magnetic fluorescent composite nanometer biological probe and preparation method thereof - Google Patents
Magnetic fluorescent composite nanometer biological probe and preparation method thereof Download PDFInfo
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- CN104762085A CN104762085A CN201510052196.3A CN201510052196A CN104762085A CN 104762085 A CN104762085 A CN 104762085A CN 201510052196 A CN201510052196 A CN 201510052196A CN 104762085 A CN104762085 A CN 104762085A
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Abstract
The invention relates to a preparation method of multifunctional nanometer composite microspheres and concretely relates to a magnetic fluorescent composite nanometer biological probe and a preparation method thereof. The nanometer composite microsphere is prepared by connecting carboxymethyl chitosan-modified magnetic nanoparticles and water soluble quantum dots through crosslinking effects of a cross-linking agent based on a natural organic polymer as a matrix, wherein the fluorescent quantum dots are distributed on the surface of the magnetic nanoparticle, the size of the magnetic nanoparticle is in a range of 10-200nm and the size of the quantum dot is in a range of 1.5-10nm, and after surface functional group modification, the nanometer composite particles can be connected to a biomolecule so that a bioprobe is formed. The preparation method allows mild reaction conditions and has simple processes. The prepared magnetic fluorescent composite nanometer particles have good magnetic properties and fluorescence properties and have a wide application prospect in the fields of biomarking, bioseparation, immunodetection, targeting release of drugs and target-oriented imaging.
Description
Technical field
The present invention relates to a kind of preparation method of multifunctional nano complex microsphere, be specifically related to a kind of magnetic fluorescence composite Nano bioprobe and preparation method thereof, this composite particles has possessed the fluorescence property of quantum dot and the magnetic property of magnetic nanoparticle simultaneously, can be used as target location and bioluminescence imaging aspect in organism.
Background technology
In biological label, luminous semiconductor-quantum-point demonstrates very large advantage.Compared with luminous organic material, luminous semiconductor-quantum-point emission spectrum is narrow, can realize from ultraviolet, can see infrared tunable radiation emitting, and have wide excitation band, the light of single wavelength can be utilized to carry out exciting and obtain the utilizing emitted light of different wave length; Meanwhile, semiconductor-quantum-point has good light stability and anti-light Bleachability, and its intrinsic narrow emission band, makes it have good measurement sensitivity.Desirable magnetic fluorescent microspheres requires to have higher specific saturation magnetization, can produce stronger fluorescence and fluorescent stability is good, Microsphere Size is controlled, narrow diameter distribution, chemical stability are good, the functional group enriched is contained on surface, and the features such as preparation technology is simple, repeatability is good, low price, it not only can be used for medical diagnosis on disease as mri contrast agent, can also be used for the separation of disease treatment and various albumen, cell etc. as pharmaceutical carrier.Therefore, if the quantum dot and magneticsubstance with fluorescence are combined, obtain a kind of novel difunctional magnetic fluorescent nanometer particle, can also carry out optical detection while separation, this has very large application potential by biomarker, bioseparation, immunodetection, drug targeting release, target imaging etc.
At present, the method preparing magnetic fluorescence composite nanometer particle is a lot, comprehensive present Research both at home and abroad, and the preparation method of fluorescence magnetic composite nano particle mainly contains following several: the first, magneticsubstance Surface coating fluorescent substance; The second, fluorescent grain Surface coating one deck magnetic substance; 3rd, two kinds of nanoparticles respectively with magnetic and fluorescence are wrapped in silicon-dioxide or other macromolecular materials simultaneously.
Through finding existing technology retrieval, Guo Guangsheng etc. (publication number: CN103372407A, title: a kind of preparation method of magnetic fluorescence composite Nano ball) pass through at Fe
3o
4particle surface is coated Si O first
2shell, then by silane resin acceptor kh-550 to Fe
3o
4@SiO
2surface is carried out amido modified, then CdSe QDs is loaded to SiO by the electrostatic force between carboxyl and amino
2surface, obtains end product magnetic fluorescence composite Nano ball.This method quantum dot is connected with magnetic nanoparticle by electrostatic attraction effect, because electrostatic force is relatively weak, quantum dot easily comes off from magnetic nanoparticle surface, simultaneously, exposed on composite nano particle surface in conjunction with rear quantum dot, quantum dot is easily subject to the impact of other factors such as environment, causes fluorescence intensity to reduce.(the publication number: CN102703601A such as Luo Yang, title: Multifunctional magnetic fluorescent microsphere and its preparation method and application) connect magnetic Nano material and quantum dot by bridging DNA, use vitamin H and marked by streptavidin DNA and magneticsubstance respectively simultaneously, utilize vitamin H and Streptavidin, amino is connected with the bonding force between carboxyl, prepare magnetic fluorescence composite nano particle, the method preparation process needs to modify particle surface by different biomolecules, make it with different functional groups, preparation process is complicated, DNA simultaneously, vitamin H and avidin require harsh to preparation and storage environment.
In order to overcome the deficiencies in the prior art, the present invention passes through reverse microemulsion process, take natural organic high-molecular as matrix, connect the sugar-modified magnetic nanoparticle of carboxymethyl chitosan and water-soluble quantum dot by the crosslinked action of linking agent, finally obtain the magnetic fluorescence composite nano particle that biocompatibility is good.Because cm-chitosan is to the modification of magnetic particle, effectively prevent the leakage of magneticsubstance and the fluorescent quenching effect to quantum dot; Take natural organic high-molecular as matrix, be wrapped in inside microballoon by quantum dot and magnetic particle, as a kind of good bio-organic carrier, it has good biocompatibility, degradability.Simultaneously organic molecule there is the reactable such as great amount of hydroxy group, amino active group, the methods such as degraded, chemical modification can be utilized to improve its solubility property, increase that it is water-soluble.
Summary of the invention
The object of this invention is to provide a kind of preparation method of magnetic fluorescence composite Nano bioprobe, composite nano particle prepared by the method has that magnetic responsiveness is strong, light stability is high, preparation is simple, good dispersity and the advantages such as size uniform, compare with magneticsubstance with the fluorescent material of simple function, the multifunctional nanocomposites simultaneously with fluorescence and magnetic has biomedical applications widely in nanometer biotechnology, as cellular segregation and identification, the analysis of cell multi-modal imaging, living imaging, biochemical marker and sensing etc.
The present invention is achieved by the following measures:
A preparation method for magnetic fluorescence composite Nano bioprobe, adopts following steps:
A () adopts blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs): 1. take 50-500mg magnetic nanoparticle and be dissolved in 30 mL pH=7.4, concentration is in the PBS buffered soln of 0.01mol/L, logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle; 2. take 10-800 mg cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.1-0.5 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; 3. will 1. and 2. two solution mixing, 25 DEG C of vibration 2-6 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 5-20 mg/mL
2solution, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites;
B () adopts reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere:
Get 5-20 mL oil phase hexanaphthene, 1-5 mL tensio-active agent Triton-100,1-5 mL cosurfactant n-hexyl alcohol and suitable quantity of water add in there-necked flask, stir 30-60min and form uniform microemulsion; Add in natural organic high-molecular solution by the 0.005-0.03 g cm-chitosan magnetic nanocomposites of preparation in step (a), ultrasonic 20-60 min, makes magnetic nanometer particles be uniformly dispersed and obtains reaction soln A; The concentrated aqueous phase quantum point getting preparation is dissolved in distilled water, obtains reaction soln B; Dropwise added in Reverse Microemulsion System by A and B, add linking agent after stirring 30-50 min, under normal temperature, stirring reaction 10-30 h, uses acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtains magnetic fluorescence composite nano-microsphere.
The magnetic fluorescence composite nanometer particle prepared in the present invention, its surface is with amino, hydroxyl and carboxyl, but for the number of functional groups connected needed for biomolecules or fewer, carboxyl, amino, sulfydryl, polyethylene glycol groups can be carried out selectivity with biomolecules and be connected, when therefore composite nanometer particle being made probe, in order to better for biologic applications, surface functional group modification can be carried out again on composite nanometer particle surface, increase the quantity of original functional group on composite particles.
Magnetic fluorescence composite nano-microsphere described in the present invention, surface functional group modification is carried out to obtained magnetic fluorescence composite nanometer particle, comprise following concrete steps: be distributed in water by magnetic fluorescence composite nanometer particle, add the alkoxysilane reagent containing functional group, stir 1-36 h, centrifugation, obtains the magnetic fluorescence composite nanometer particle that surface functional group is modified, alkoxysilane reagent containing functional group used comprises: aminopropyl trimethoxysilane, aminoethyl Trimethoxy silane, aminomethyl Trimethoxy silane, aminopropyl triethoxysilane, aminoethyl triethoxyl silane, aminomethyl triethoxyl silane, aminomethyl tripropoxy silane, aminoethyl tripropoxy silane, aminopropyl tripropoxy silane, mercaptopropyl trimethoxysilane, mercapto ethyl trimethoxy silane, thiopurine methyltransferase Trimethoxy silane, mercaptopropyltriethoxysilane, mercaptoethyltriethoxysilane, thiopurine methyltransferase triethoxyl silane, thiopurine methyltransferase tripropoxy silane, mercapto ethyl tripropoxy silane, mercapto propyl group tripropoxy silane.
Magnetic nanoparticle (MNPs) described in the present invention, for having superparamagnetic, paramagnetic or ferromagnetic metal and metal oxide, is selected from Fe
3o
4, Fe
2o
3, MeFe
2o
4(Me=Co, Mn, Ni), compound neodymium iron boron, SmCo etc., metal Fe, Co, Ni and alloy Fe
2co, Ni
2the nano particle of the metal oxide of Fe.
The particle diameter of the magnetic fluorescence composite nano-microsphere described in the present invention is 10-220 nm.
The preparation method of the magnetic nanoparticle described in the present invention comprises coprecipitation method, hydrothermal method.
Quantum dot described in the present invention is the water-soluble quantum dot of surface with hydrophilic radical, and quantum dot is II-VI, III-V group semi-conductor material, or is the matrix material that II-VI and III-V group semi-conductor material are formed, and described quantum point grain diameter is 1.5-10 nm; Preferred quantum dot is ZnSe, CdSe, CdTe, CdS, ZnSe/ZnS, CdS/ZnS, CdSe/ZnS, CdTe/ZnS, Zn
xcd
1-Xse, CdSe
1-Xs
x, CdSe
1-Xte
x, CdSe/ZnSe, CdS/ZnSe, CdTe/ZnSe, CdSe/CdS, CdTe/CdS, CdS/Zn
xcd
1-Xs, ZnSe/Zn
xcd
1-Xs, CdSe/Zn
xcd
1-Xs, CdTe/Zn
xcd
1-Xs, wherein 0 < X < 1.
Natural organic high-molecular described in the present invention comprises chitosan, cm-chitosan, gelatin.
Magnetic fluorescence composite nano-microsphere described in the present invention, in step (a), the molecular weight of cm-chitosan is 2 × 10
5-2.5 × 10
5, the thickness of cm-chitosan on magnetic nanoparticle surface is 3-10 nm.
Magnetic fluorescence composite nano-microsphere of the present invention, in step (b) linking agent comprise formaldehyde, oxalic dialdehyde, glutaraldehyde, concentration is 4%-15%.
Magnetic fluorescence composite nano-microsphere of the present invention, in step (b), the mol ratio of cm-chitosan magnetic nanocomposites and quantum dot is 1:1-1:20.
Magnetic nanoparticle surface of the present invention is containing at least one in hydroxyl, amino, carboxyl.
Quantum dot surface of the present invention contains at least one in sulfydryl, carboxyl, amino; The hydrophilic radical part used in semiconductor-quantum-point synthesis comprises 3-thiohydracrylic acid, Thiovanic acid, Cys, 2 mercaptopropionic acid, mercaptobutyric acid, mercaptopentanoic acid, mercaptohexanoic acid, dimercaptosuccinic acid, mercaptoethanol, mercaprol, mercaptoethylamine.
Natural organic high-molecular of the present invention, chitosan solution is by Chitosan powder ultrasonic disperse 30min in the weakly acid soln of 2%-6%, is made into the chitosan gel rubber solution of 0.002-0.01 g/mL; Gelatin solution is dissolved in the water-bath of 40-70 DEG C by gelatin powder, and configuration volume fraction is the aqueous gelatin solution of 5%-15%; Carboxymethyl chitosan solution is dissolved in distilled water by cm-chitosan, is made into the carboxymethyl chitosan solution of 0.002-0.04 g/mL.
Weakly acid soln of the present invention comprises formic acid, Glacial acetic acid, tartrate, citric acid.
Magnetic fluorescence composite Nano bioprobe in the present invention, be the magnetic fluorescence composite nanometer particle of surface functional group modification and biomolecules are connected to form, described biomolecules comprises protein molecule, antibody antigen molecule, DNA molecular, enzyme etc.; Wherein the concentration of magnetic fluorescence composite nanometer particle is 0.001-0.1 g/mL.
beneficial effect of the present invention:
(1) the present invention is by reverse microemulsion process, and magnetic fluorescence composite nanometer particle is prepared in chemically crosslinked effect, the even particle size distribution of composite particles, magnetic property and fluorescence property excellence.The preparation method's process adopted is simple, easily operates, can be applied to the preparation of the magnetic fluorescence composite Nano ball of other kind easily.
(2) the present invention is by the modification of cm-chitosan to magnetic particle, effectively prevent the leakage of magneticsubstance and the fluorescent quenching effect to quantum dot; Simultaneously there is the natural organic high-molecular of good biocompatibility for matrix, add the biological activity of composite nano particle, make composite nano particle can be widely used in the fields such as biomarker, bio-imaging and bioseparation.
(3) the magnetic fluorescence composite Nano bioprobe that prepared by the present invention can realize fluorescent mark to biomolecules and magnetic resolution simultaneously, is conducive to enrichment and the bio-imaging of biomolecules, expands the Application Areas of bioprobe.
Accompanying drawing explanation
The TEM photo of Fig. 1 magnetic fluorescence composite nano-microsphere
The fluorescence spectrum of Fig. 2 magnetic fluorescence composite nano-microsphere and absorption spectrum
Magnetic fluorescence composite nano-microsphere prepared by Fig. 3 different mol ratio
Fig. 4 CdTe@ZnS-Fe
2o
3the fluorescence spectrum of magnetic fluorescence composite nano-microsphere and absorption spectrum
The digital photograph of Fig. 5 magnetic fluorescence composite nano-microsphere
The magnetic hysteresis loop of Fig. 6 magnetic fluorescence composite nano-microsphere.
Embodiment
Below by specific embodiment, technical scheme of the present invention is described, but technical scheme of the present invention is not limited with specific embodiment.
Embodiment 1:
1.1 adopt Aqueous phase to prepare ZnSe quantum dot.Under nitrogen protection, by 0.01g NaBH
4be dissolved in 2 mL distilled water with 0.0061g Se powder, be heated to 40 DEG C, after dissolving completely, obtain NaHSe solution; Get 0.0439 g Zn (Ac)
2dissolve in 20 mL distilled water, after it dissolves completely, add reduced glutathion 0.0737g, regulate pH=11.5 by the NaOH solution of 1mol/L, obtain the precursor solution of Zn; Proceed in there-necked flask by the presoma of Zn, inject NaHSe solution rapidly under nitrogen protection, oil bath 100 DEG C backflow, after magnetic agitation 1h, taking-up is put into refrigerator and is quickly cooled to room temperature, obtains colourless transparent solution, is the ZnSe QDs solution prepared.
1.2 adopt hydrothermal method to prepare Fe
3o
4nano particle.Take 3 g FeCl
3be dissolved in 80 mL ethylene glycol and stir ultrasonic dissolution, add polyoxyethylene glycol 2 g that molecular weight is 2000, sodium-acetate 7 g, stir ultrasonic making it to dissolve, precursor solution is proceeded in hydrothermal reaction kettle, at 200 DEG C of reaction 5 h, after having reacted, gained solution with water and dehydrated alcohol are alternately washed, through vacuum-drying, obtain dry Fe
3o
4magnetic nanometer particles.
1.3 adopt blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs).Take 0.2 g Fe
3o
4magnetic nanoparticle is dissolved in 30 mL pH=7.4, and concentration is in the PBS buffered soln of 0.01mol/L, and logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle, obtain finely dispersed Fe
3o
4nanoparticles solution; Take 0.5 g cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.3 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; Afterwards carboxymethyl chitosan solution is added Fe
3o
4nanoparticles solution, 25 DEG C of vibration 3 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 10 mg/mL
2solution 5 mL, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites.
1.4 Chitosan powder are ultrasonic disperse 30min in the glacial acetic acid solution of 3%, is made into the chitosan gel rubber solution of 0.002 g/mL.
1.5 adopt reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere.Get 10 mL oil phase hexanaphthenes, 2.5 mL tensio-active agent Triton-100,2.5 mL cosurfactant n-hexyl alcohols and 1 mL water add in there-necked flask, stir 30 min and form uniform microemulsion; Join in the chitosan gel rubber solution of 0.002 g/mL by 0.01 g cm-chitosan magnetic nanocomposites of preparation in step 1.3, ultrasonic 60 min, make magnetic nanometer particles be uniformly dispersed, and obtain reaction soln A; Get the aqueous phase ZnSe quantum dot of preparation in 1.1, be dissolved in after Virahol separating-purifying in 2mL distilled water, obtain reaction soln B, wherein ZnSe quantum dot concentration is 5 × 10
-2mol/L; A and B is added in Reverse Microemulsion System, after stirring 30-50 min, add 10 μ L glutaraldehyde (concentration is 10 %), stirring reaction 12 h under normal temperature, use acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtain magnetic fluorescence composite nano-microsphere.Fig. 1 is the TEM photo of magnetic fluorescence composite nano-microsphere.
1.6 magnetic fluorescence composite nano-microspheres step 1.5 prepared are distributed in water, add aminopropyl trimethoxysilane, stir 10h, afterwards centrifugation, obtain the composite nanometer particle that surface functional group is modified.
It is in the PBS buffered soln of 7.4 that the composite nanometer particle that 1.7 surface functional groups step 1.6 prepared are modified is distributed to pH, and wherein liquor capacity is 5mL, and the concentration of composite nanometer particle is 0.005g/mL; Adopt different chemical processes at composite nanometer particle surface-binding matter molecule.
Embodiment 2:
The preparation of 2.1 ZnSe@ZnS quantum dot solution.First adopt chemical coprecipitation to prepare ZnSe quantum dot, preparation method is as described in above-described embodiment 1.Get ZnSe quantum dot 15 mL prepared, wherein the concentration of ZnSe quantum dot is 2.7 × 10
-3mol/L, adds 0.0138 g Zn (Ac)
2, 0.0277 g reductive glutathione and 0.01 g thiocarbamide, be 1 mol/L NaOH solution adjust ph by the concentration configured be 10.5, under magnetic stirring, oil bath 100 DEG C backflow, magnetic agitation is put into refrigerator after reacting 2 h and is quickly cooled to room temperature, obtains the ZnSe@ZnS quantum dot of faint yellow water-soluble high-luminous-efficiency.
2.2 adopt hydrothermal method to prepare Fe
3o
4nano particle.Get 2.78 g FeSO
47H
2o, 4.32 g FeCl
36H
2o is dissolved in 30 mL distilled water; after magnetic agitation is dissolved; add 30 mL ethylene glycol again; after stirring under nitrogen protection; add in there-necked flask, regulate pH to 9-11 by the NaOH solution that the concentration configured is 2 mol/L, add tensio-active agent polyvinylpyrrolidone 0.15 g; 30min is reacted, obtained Fe after abundant stirring
3o
4the presoma of magnetic nanometer particles.By Fe
3o
4the presoma of magnetic nanometer particles proceeds in hydrothermal reaction kettle, at 160 DEG C, react 6h.After having reacted, gained solution with water and dehydrated alcohol are alternately washed, through vacuum-drying, obtain dry Fe
3o
4magnetic nanometer particles.
2.3 adopt blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs).Take 0.3 g Fe
3o
4magnetic nanoparticle is dissolved in 30 mL pH=7.4, and concentration is in the PBS buffered soln of 0.01mol/L, and logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle, obtain finely dispersed Fe
3o
4nanoparticles solution; Take 0.7 g cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.4 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; Afterwards carboxymethyl chitosan solution is added Fe
3o
4nanoparticles solution, 25 DEG C of vibration 5 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 15 mg/mL
2solution 5 mL, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites.
Gelatin powder dissolves by 2.4 in the water-bath of 60 DEG C, and configuration volume fraction is the aqueous gelatin solution of 10%.
2.5 adopt reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere.Get 15 mL oil phase hexanaphthenes, 2.7 mL tensio-active agent Triton-100,2.7 mL cosurfactant n-hexyl alcohols and 1 mL water add in there-necked flask, stir 30 min and form uniform microemulsion; Join in the aqueous gelatin solution of 10 % by 0.015 g cm-chitosan magnetic nanocomposites of preparation in step 2.3, ultrasonic 60 min, make magnetic nanometer particles be uniformly dispersed, and obtain reaction soln A; Get the aqueous phase ZnSe@ZnS quantum dot of preparation in 2.1, be dissolved in after Virahol separating-purifying in 2mL distilled water, obtain reaction soln B, wherein ZnSe@ZnS quantum dot concentration is 0.2 mol/L; A and B is added in Reverse Microemulsion System, after stirring 30-50 min, add 15 μ L oxalic dialdehydes (concentration is 8 %), stirring reaction 15 h under normal temperature, use acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtain magnetic fluorescence composite nano-microsphere.Fig. 2 is fluorescence spectrum and the absorption spectrum of the magnetic fluorescence composite nano-microsphere of preparation.
2.6 magnetic fluorescence composite nano-microspheres step 2.5 prepared are distributed in water, add mercapto ethyl trimethoxy silane, stir 15h, afterwards centrifugation, obtain the composite nanometer particle that surface functional group is modified.
It is in the PBS buffered soln of 7.4 that the composite nanometer particle that 2.7 surface functional groups step 2.6 prepared are modified is distributed to pH, and wherein liquor capacity is 5mL, and the concentration of composite nanometer particle is 0.01g/mL; Different chemical processes is adopted to connect antigen molecule on composite nanometer particle surface.
Embodiment 3:
3.1 aqueous phases prepare CdTe quantum.Under nitrogen protection, by 0.0945g NaBH
4be dissolved in 5 mL distilled water with 0.0063g Te powder, be heated to 40 DEG C, after dissolving completely, obtain NaHTe solution; Get 0.293 g Cd (Ac)
2dissolve in 100 mL distilled water, after it dissolves completely, add 2.0 mmol, regulate pH=11 by the NaOH solution of 1mol/L, obtain the precursor solution of Cd; Proceed in there-necked flask by the presoma of Cd, inject NaHTe solution rapidly under nitrogen protection, oil bath 100 DEG C backflow, after magnetic agitation 6h, taking-up is put into refrigerator and is quickly cooled to room temperature, obtains colourless transparent solution, is the CdTe QDs solution prepared.
The preparation of 3.2 magnetic nanoparticles.Employing patent publication No. is that the method for CN101597495A prepares Fe
3o
4/ CoO core-shell structure magnetic nano particle.
3.3 adopt blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs).Take 0.4 g Fe
3o
4/ CoO magnetic nanoparticle is dissolved in 30 mL pH=7.4, and concentration is in the PBS buffered soln of 0.01mol/L, and logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle, obtain finely dispersed Fe
3o
4/ CoO nanoparticles solution; Take 0.8 g cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.4 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; Afterwards carboxymethyl chitosan solution is added Fe
3o
4/ CoO nanoparticles solution, 25 DEG C of vibration 5 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 10 mg/mL
2solution 5 mL, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites.
Cm-chitosan is dissolved in distilled water by 3.4, is made into the carboxymethyl chitosan solution of 0.01 g/mL.
3.5 adopt reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere.Get 15 mL oil phase hexanaphthenes, 2.7 mL tensio-active agent Triton-100,2.7 mL cosurfactant n-hexyl alcohols and 1 mL water add in there-necked flask, stir 30 min and form uniform microemulsion; Join in the carboxymethyl chitosan solution of 0.01 g/mL by 0.02 g cm-chitosan magnetic nanocomposites of preparation in step 3.3, ultrasonic 60 min, make magnetic nanometer particles be uniformly dispersed, and obtain reaction soln A; Get the aqueous phase CdTe quantum of preparation in 3.1, be dissolved in after Virahol separating-purifying in 2mL distilled water, obtain reaction soln B, wherein CdTe quantum concentration is 0.4 mol/L; A and B is added in Reverse Microemulsion System, after stirring 30-50 min, add 15 μ L oxalic dialdehydes (concentration is 12%), stirring reaction 18 h under normal temperature, use acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtain magnetic fluorescence composite nano-microsphere.Fig. 3 is magnetic fluorescence composite nano-microsphere prepared by different mol ratio.
3.6 magnetic fluorescence composite nano-microspheres step 3.5 prepared are distributed in water, add aminopropyl triethoxysilane, stir 20h, afterwards centrifugation, obtain the composite nanometer particle that surface functional group is modified.
It is in the PBS buffered soln of 7.4 that the composite nanometer particle that 3.7 surface functional groups step 3.6 prepared are modified is distributed to pH, and wherein liquor capacity is 5mL, and the concentration of composite nanometer particle is 0.05g/mL; Different chemical processes is adopted to connect antibody molecule on composite nanometer particle surface.
Embodiment 4:
4.1 adopt Aqueous phase to prepare CdTe ZnS quantum dot. and first adopt chemical coprecipitation to prepare CdTe quantum, preparation method is as described in above-described embodiment 3, and difference is the reaction times is 2h.Getting the CdTe quantum prepared is dissolved in 30 mL distilled water, and wherein the concentration of CdTe quantum is 1.67 × 10
-3mol/L, adds 0.0352 g Zn (Ac)
2, 0.0984 g reductive glutathione, be 1 mol/L NaOH solution adjust ph by the concentration configured be 8, under magnetic stirring, oil bath 100 DEG C backflow, magnetic agitation is put into refrigerator after reacting 2 h and is quickly cooled to room temperature, obtains the CdTe@ZnS quantum dot of water-soluble high-luminous-efficiency.
The preparation of 4.2 magnetic nanoparticles.Employing patent publication No. is that the method for CN 101928043 A prepares α-Fe
2o
3magnetic nanoparticle.
4.3 adopt blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs).Take 0.3 g α-Fe
2o
3magnetic nanoparticle is dissolved in 30 mL pH=7.4, and concentration is in the PBS buffered soln of 0.01mol/L, and logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle, obtain finely dispersed α-Fe
2o
3nanoparticles solution; Take 0.6 g cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.4 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; Afterwards carboxymethyl chitosan solution is added α-Fe
2o
3nanoparticles solution, 25 DEG C of vibration 3 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 15 mg/mL
2solution 5 mL, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites.
4.4 Chitosan powder are ultrasonic disperse 30min in the citric acid solution of 4%, is made into the chitosan gel rubber solution of 0.005 g/mL.
4.5 adopt reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere.Get 20 mL oil phase hexanaphthenes, 5 mL tensio-active agent Triton-100,5 mL cosurfactant n-hexyl alcohols and 1.5 mL water add in there-necked flask, stir 30 min and form uniform microemulsion; Join in the chitosan solution of 0.005 g/mL by 0.03 g cm-chitosan magnetic nanocomposites of preparation in step 4.3, ultrasonic 60 min, make magnetic nanometer particles be uniformly dispersed, and obtain reaction soln A; Get the aqueous phase CdTe@ZnS quantum dot of preparation in 4.1, be dissolved in after Virahol separating-purifying in 2 mL distilled water, obtain reaction soln B, wherein CdTe@ZnS quantum dot concentration is 0.8 mol/L; A and B is added in Reverse Microemulsion System, after stirring 30-50 min, add 15 μ L glutaraldehyde (concentration is 15%), stirring reaction 24 h under normal temperature, use acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtain magnetic fluorescence composite nano-microsphere.Fig. 4 is the CdTe@ZnS-Fe of preparation
2o
3the fluorescence spectrum of magnetic fluorescence composite nano-microsphere and absorption spectrum; Fig. 5 is the digital photograph of magnetic fluorescence composite nano-microsphere.
4.6 magnetic fluorescence composite nano-microspheres step 4.5 prepared are distributed in water, add mercaptopropyltriethoxysilane, stir 25h, afterwards centrifugation, obtain the composite nanometer particle that surface functional group is modified.
It is in the PBS buffered soln of 7.4 that the composite nanometer particle that 4.7 surface functional groups step 4.6 prepared are modified is distributed to pH, and wherein liquor capacity is 5mL, and the concentration of composite nanometer particle is 0.08g/mL; Different chemical processes is adopted to connect DNA molecular on composite nanometer particle surface.
Embodiment 5:
5.1 adopt Aqueous phase to prepare CdSe quantum dot. under nitrogen protection, by 0.0106 g NaBH
4be dissolved in 2 mL distilled water with 0.0063 g Se powder, be heated to 40 DEG C, after dissolving completely, obtain NaHSe solution; Get 0.0533 g Cd (Ac)
2dissolve in 20 mL distilled water, after it dissolves completely, add 1.0 mmol, regulate pH=11.5 by the NaOH solution of 1mol/L, obtain the precursor solution of Cd; Proceed in there-necked flask by the presoma of Cd, inject NaHSe solution rapidly under nitrogen protection, oil bath 100 DEG C backflow, after magnetic agitation 1h, taking-up is put into refrigerator and is quickly cooled to room temperature, obtains colourless transparent solution, is the CdSe QDs solution prepared.
The preparation of 5.2 magnetic nanoparticles.Get 1.39 g FeSO
47H
2o, 2.16 g FeCl
36H
2o is dissolved in 50 mL distilled water; after magnetic agitation is dissolved; under nitrogen protection; add in there-necked flask, heating in water bath to 80 DEG C, under mechanical stirring; add tensio-active agent polyvinylpyrrolidone 0.1 g; regulate pH to 9-11 with the ammonia soln that the concentration configured is 15%, after fully stirring, react 60min, obtained Fe
3o
4magnetic nanometer particles.After having reacted, gained solution with water and dehydrated alcohol are alternately washed, through vacuum-drying, obtain dry Fe
3o
4magnetic nanometer particles.
5.3 adopt blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs).Take 0.3 g Fe
3o
4magnetic nanoparticle is dissolved in 30 mL pH=7.4, and concentration is in the PBS buffered soln of 0.01mol/L, and logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle, obtain finely dispersed Fe
3o
4nanoparticles solution; Take 0.8 g cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.4 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; Afterwards carboxymethyl chitosan solution is added Fe
3o
4nanoparticles solution, 25 DEG C of vibration 4 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 10 mg/mL
2solution 5 mL, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites.
5.4 Chitosan powder are ultrasonic disperse 30min in the glacial acetic acid solution of 3%, is made into the chitosan gel rubber solution of 0.01 g/mL.
5.5 adopt reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere.Get 20 mL oil phase hexanaphthenes, 5 mL tensio-active agent Triton-100,5 mL cosurfactant n-hexyl alcohols and 1.5 mL water add in there-necked flask, stir 30 min and form uniform microemulsion; Join in the chitosan solution of 0.01 g/mL by 0.03 g cm-chitosan magnetic nanocomposites of preparation in step 5.3, ultrasonic 60 min, make magnetic nanometer particles be uniformly dispersed, and obtain reaction soln A; Get the aqueous phase CdSe quantum dot of preparation in 5.1, be dissolved in after Virahol separating-purifying in 2 mL distilled water, obtain reaction soln B, wherein CdSe quantum dot concentration is 1.0 mol/L; A and B is added in Reverse Microemulsion System, after stirring 30-50 min, add 15 μ L oxalic dialdehydes (concentration is 15%), stirring reaction 24 h under normal temperature, use acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtain magnetic fluorescence composite nano-microsphere.Fig. 6 is the magnetic hysteresis loop of the magnetic fluorescence composite nano-microsphere of preparation.
5.6 magnetic fluorescence composite nano-microspheres step 5.5 prepared are distributed in water, add aminomethyl triethoxyl silane, stir 30h, afterwards centrifugation, obtain the composite nanometer particle that surface functional group is modified.
It is in the PBS buffered soln of 7.4 that the composite nanometer particle that 5.7 surface functional groups step 5.6 prepared are modified is distributed to pH, and wherein liquor capacity is 5mL, and the concentration of composite nanometer particle is 0.1g/mL; Adopt different chemical processes at composite nanometer particle surface ligase enzyme molecule.
Claims (10)
1. the preparation method of a magnetic fluorescence composite nano-microsphere, it is characterized in that, this composite nano-microsphere take natural organic high-molecular as matrix, by the crosslinked action at linking agent magnetic nanoparticle sugar-modified for carboxymethyl chitosan is connected with water-soluble quantum dot and obtains, described fluorescence quantum is distributed in the surface of magnetic nanoparticle, wherein the size of magnetic nanoparticle is at 10-200 nm, and the particle diameter of quantum dot is at 1.5-10 nm.
2. a kind of magnetic fluorescence composite nano-microsphere according to claim 1, it is characterized in that, described preparation method comprises the following steps:
A () adopts blended entrapping method to prepare cm-chitosan magnetic nanocomposites (CMCH-MNPs): 1. take 50-500mg magnetic nanoparticle and be dissolved in 30 mL pH=7.4, concentration is in the PBS buffered soln of 0.01mol/L, logical nitrogen deoxidation, utilizes Ultrasonic Cleaners to be uniformly dispersed by magnetic particle; 2. take 10-800 mg cm-chitosan to be dissolved in the buffered soln of 20 mL PBS=7.4, add the group that 0.1-0.5 g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) activates cm-chitosan surface simultaneously; 3. will 1. and 2. two solution mixing, 25 DEG C of vibration 2-6 h in water bath with thermostatic control vibrator, in earthquake process, slowly instillation concentration is the CaCl of 5-20 mg/mL
2solution, it is blended coated to carry out ionomer, and reaction terminates rear magnet and collects product, then uses distilled water and PBS (pH=7.4) buffered soln fully to wash successively, namely obtains cm-chitosan magnetic nanocomposites;
B () adopts reverse microemulsion process to prepare magnetic fluorescence composite nano-microsphere:
Get 5-20 mL oil phase hexanaphthene, 1-5 mL tensio-active agent Triton-100,1-5 mL cosurfactant n-hexyl alcohol and suitable quantity of water add in there-necked flask, stir 30-60min and form uniform microemulsion; Join in the solution of natural organic high-molecular by the 0.005-0.03 g cm-chitosan magnetic nanocomposites of preparation in step (a), ultrasonic 20-60 min, makes magnetic nanometer particles be uniformly dispersed and obtains reaction soln A; The concentrated aqueous phase quantum point getting preparation is dissolved in distilled water, obtains reaction soln B; Dropwise added in Reverse Microemulsion System by A and B, add linking agent after stirring 30-50 min, under normal temperature, stirring reaction 10-30 h, uses acetone breakdown of emulsion, centrifugation, more successively with ethanol and distilled water alternately washing, namely obtains magnetic fluorescence composite nano-microsphere.
3. a kind of magnetic fluorescence composite nano-microsphere according to claim 1 and 2, it is characterized in that, the magnetic fluorescence composite nanometer particle obtained carries out surface functional group modification, comprise following concrete steps: be distributed in water by magnetic fluorescence composite nanometer particle, add the alkoxysilane reagent containing functional group, stir 1-36 h, centrifugation, obtain the magnetic fluorescence composite nanometer particle that surface functional group is modified, alkoxysilane reagent containing functional group used comprises: aminopropyl trimethoxysilane, aminoethyl Trimethoxy silane, aminomethyl Trimethoxy silane, aminopropyl triethoxysilane, aminoethyl triethoxyl silane, aminomethyl triethoxyl silane, aminomethyl tripropoxy silane, aminoethyl tripropoxy silane, aminopropyl tripropoxy silane, mercaptopropyl trimethoxysilane, mercapto ethyl trimethoxy silane, thiopurine methyltransferase Trimethoxy silane, mercaptopropyltriethoxysilane, mercaptoethyltriethoxysilane, thiopurine methyltransferase triethoxyl silane, thiopurine methyltransferase tripropoxy silane, mercapto ethyl tripropoxy silane, mercapto propyl group tripropoxy silane.
4. the preparation of a kind of magnetic fluorescence composite nano-microsphere according to claim 1 and 2, is characterized in that, the particle diameter of described magnetic fluorescence composite nano-microsphere is 10-220 nm; Described magnetic nanoparticle (MNPs) is superparamagnetic, paramagnetic or ferromagnetic metal and metal oxide, is selected from Fe
3o
4, Fe
2o
3, MeFe
2o
4(Me=Co, Mn, Ni), compound neodymium iron boron, SmCo etc., metal Fe, Co, Ni and alloy Fe
2co, Ni
2the nano particle of the metal oxide of Fe; The preparation method of magnetic nanoparticle comprises coprecipitation method, hydrothermal method; Magnetic nanoparticle surface is containing at least one in hydroxyl, amino, carboxyl.
5. a kind of magnetic fluorescence composite nano-microsphere according to claim 1 and 2, it is characterized in that, described quantum dot is the water-soluble quantum dot of surface with hydrophilic radical, quantum dot is II-VI, III-V group semi-conductor material, or be the matrix material that II-VI and III-V group semi-conductor material are formed, described quantum point grain diameter is 1.5-10 nm; Preferred quantum dot is ZnSe, CdSe, CdTe, CdS, ZnSe/ZnS, CdS/ZnS, CdSe/ZnS, CdTe/ZnS, Zn
xcd
1-Xse, CdSe
1-Xs
x, CdSe
1-Xte
x, CdSe/ZnSe, CdS/ZnSe, CdTe/ZnSe, CdSe/CdS, CdTe/CdS, CdS/Zn
xcd
1-Xs, ZnSe/Zn
xcd
1-Xs, CdSe/Zn
xcd
1-Xs, CdTe/Zn
xcd
1-Xs, wherein 0 < X < 1.
6. a kind of magnetic fluorescence composite nano-microsphere according to claim 1 and 2, it is characterized in that, described natural organic high-molecular comprises chitosan, cm-chitosan, gelatin; Chitosan solution is by Chitosan powder ultrasonic disperse 30min in the weakly acid soln of 2%-6%, is made into the chitosan gel rubber solution of 0.002-0.01 g/mL; Gelatin solution is dissolved in the water-bath of 40-70 DEG C by gelatin powder, and configuration volume fraction is the aqueous gelatin solution of 5%-15%; Carboxymethyl chitosan solution is dissolved in distilled water by cm-chitosan, is made into the carboxymethyl chitosan solution of 0.002-0.04 g/mL.
7. a kind of magnetic fluorescence composite nano-microsphere according to claim 2, is characterized in that, in step (a), the molecular weight of cm-chitosan is 2 × 10
5-2.5 × 10
5, the thickness of cm-chitosan on magnetic nanoparticle surface is 3-10 nm; In step (b) linking agent comprise formaldehyde, oxalic dialdehyde, glutaraldehyde, concentration is 4%-15%; In step (b), the mol ratio of cm-chitosan magnetic nanocomposites and quantum dot is 1:1-1:20.
8. the preparation of water-soluble quantum dot according to claim 5, is characterized in that: described quantum dot surface contains at least one in sulfydryl, carboxyl, amino; The hydrophilic radical part used in semiconductor-quantum-point synthesis comprises 3-thiohydracrylic acid, Thiovanic acid, Cys, 2 mercaptopropionic acid, mercaptobutyric acid, mercaptopentanoic acid, mercaptohexanoic acid, dimercaptosuccinic acid, mercaptoethanol, mercaprol, mercaptoethylamine.
9. the preparation of natural organic high-molecular solution according to claim 6, is characterized in that, described weakly acid soln comprises formic acid, Glacial acetic acid, tartrate, citric acid.
10. a magnetic fluorescence composite Nano bioprobe, it is characterized in that, the magnetic fluorescence composite nanometer particle modify the surface functional group described in claim 1-3 and biomolecules are connected to form, and described biomolecules comprises protein molecule, antibody antigen molecule, DNA molecular, enzyme etc.; Wherein the concentration of magnetic fluorescence composite nanometer particle is 0.001-0.1 g/mL.
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2015
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Non-Patent Citations (2)
| Title |
|---|
| 丁永玲: "磁性荧光复合纳米粒子的制备与性能表征", 《中国优秀硕士学位论文全文数据库(工程科技I辑)》 * |
| 林英等: "壳聚糖基荧光纳米微球的合成及性质", 《安徽工程大学学报》 * |
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