CN117866156A - Fluorescent microsphere with uniform particle size and preparation method thereof - Google Patents
Fluorescent microsphere with uniform particle size and preparation method thereof Download PDFInfo
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- CN117866156A CN117866156A CN202311421692.2A CN202311421692A CN117866156A CN 117866156 A CN117866156 A CN 117866156A CN 202311421692 A CN202311421692 A CN 202311421692A CN 117866156 A CN117866156 A CN 117866156A
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Abstract
The application provides a fluorescent microsphere with uniform particle size and a preparation method thereof, wherein the particle size of the fluorescent microsphere is uniform and adjustable; the fluorescent material has good luminous performance; the shell of the coating shell has good tolerance and tight coating, and the fluorescent material is not easy to leak, and the shell is resistant to water and oxygen. The preparation method comprises the following steps: s1, combining a template substance with a fluorescent material to form an inner core, wherein the template substance is a symmetrical substance with a cavity; s2, carrying out ligand modification on the inner core to form a modified inner core; s3, mixing the modified kernel with a monomer, wherein the modified kernel is dissolved in the monomer; and (3) carrying out polymerization reaction on the monomer to form the fluorescent microsphere with the shell layer coating the modified core.
Description
Technical Field
The application belongs to the technical field of fluorescent microspheres, and particularly relates to a fluorescent microsphere with uniform particle size and a preparation method thereof.
Background
The fluorescent microsphere or fluorescent biological microsphere is prepared by wrapping fluorescent materials such as quantum dots inside the microsphere or connecting and fixing fluorescent substances on the surface of the microsphere, so that nonspecific adsorption is reduced, and groups such as carboxyl, amino, hydroxyl and the like are modified on the surface of the microsphere, so that the fluorescent microsphere has water solubility and can be connected with biomolecules. The fluorescent material is excited by light or electricity to emit fluorescence, and can form a plurality of different luminous wave bands (colors) by means of different fluorescent component types and fluorescent contents, so that the fluorescent material can be used for detecting different biological molecules, for example, biological medicine fields such as biological markers, disease diagnosis, tracers, solid-phase chips, liquid-phase chips, immunochromatography, raman scattering and the like, and has huge application prospects.
The fluorescent material mainly comprises: organic fluorescent dyes, quantum dots, and metal oxides. The organic fluorescent dye is easy to degrade and photobleaching, and the prepared fluorescent microsphere plays a role in protection. However, under the irradiation of high temperature and strong light, the fluorescent quenching is easy, and the mutual quenching is easy to occur between the organic fluorescent dyes; in addition, the self-luminescence of proteins is also prone to overlap of the spectra of organic fluorescent dyes, resulting in erroneous decoding. The quantum dot is also called as semiconductor nano crystal, and the grain diameter is between 1 nm and 20 nm. The quantum dot has the excellent optical characteristics of high quantum efficiency, high photochemical stability, difficult photolysis, wide excitation, narrow emission, high color purity, adjustable luminescence color by controlling the size of the quantum dot and the like, and is widely applied to the fields of luminescent displays, photovoltaic devices and biology. However, the quantum dots have the defects of no water resistance and no oxygen resistance, and the prepared fluorescent microspheres are difficult to balance among quantum dot leakage, fluorescence quenching and sensitivity, and have the technical problem of poor stability of production batches.
In the existing preparation method of the fluorescent microsphere, if inorganic matter with compact shell layers is used for coating the fluorescent material, substances which cause adverse effects on the fluorescent material are added and formed in the hydrolysis and condensation process of the shell layer raw material, so that fluorescence quenching is caused; in addition, the inorganic shell layer has poor water resistance and is easy to permeate, and the quantum dot is easy to be influenced by water and oxygen. If the self-assembly is adopted to form the microsphere, the microsphere mainly depends on adsorption and polymer winding, the coating is not tight, the quantum dot is easy to leak, and water and oxygen can also influence the quantum dot. Meanwhile, the fluorescent microspheres in the prior art have the problem of uneven particle size of the fluorescent microspheres, and the problems of poor repeatability of results caused by uneven particle size of the fluorescent microspheres still exist in the aspect of improving the uniformity of the particle size of the fluorescent microspheres, for example, adjusting the types of solvents in a system, adjusting the proportion of components in the system, adjusting the ultrasonic power and the duration for forming micro-droplets, adjusting the stirring rate and the like. And the particle size of the fluorescent microsphere is not adjustable or the adjustable range is small. In addition, the preparation of the fluorescent microsphere is difficult to simultaneously achieve the luminous efficiency, the shell compactness and the shell tolerance of the fluorescent material.
In view of the above, the present application provides a fluorescent microsphere with uniform particle size and a preparation method thereof, wherein the fluorescent microsphere has uniform particle size and adjustable particle size; the fluorescent material has good luminous performance; the shell of the coating shell has good tolerance (shell tolerance), the coating is tight, the fluorescent material is not easy to leak, and the shell is resistant to water and oxygen.
Disclosure of Invention
The purpose of the application is to provide a fluorescent microsphere with uniform particle size and a preparation method thereof, wherein the particle size of the fluorescent microsphere is uniform and adjustable; the fluorescent material has good luminous performance; the shell of the coating shell has good tolerance and tight coating, and the fluorescent material is not easy to leak, and the shell is resistant to water and oxygen.
In a first aspect of the present application, a method for preparing fluorescent microspheres with uniform particle size is provided, including the steps of:
s1, combining a template substance with a fluorescent material to form an inner core, wherein the template substance is a symmetrical substance with a cavity;
s2, carrying out ligand modification on the inner core to form a modified inner core;
s3, mixing the modified kernel with a monomer, wherein the modified kernel is dissolved in the monomer; and (3) carrying out polymerization reaction on the monomer to form the fluorescent microsphere with the shell layer coating the modified core.
In some embodiments, in step S1, the core includes one template substance and a plurality of fluorescent materials, i.e., one template substance binds a plurality of fluorescent materials.
In some embodiments, in step S1, a mass ratio of template substance to fluorescent material is added of 1 (0.1-5). Preferably, in step S1, the mass ratio of the template substance to the fluorescent material is 1 (0.5-2.5).
In some embodiments, the template material is a rigid template material or a non-rigid template material. The template material controls the size of the template material by controlling its branch length.
Further, the rigid template substance includes: one of dendritic fibrous silica, silica having pore size, dendritic zirconium dioxide, dendritic titanium dioxide, crosslinked rigid polymer, the non-rigid template material comprising: dendritic polymers.
In some embodiments, the template material is a surface-modified template material having a coordinating group attached or adsorbed to the fluorescent material.
Further, the content of the coordinating group on the template substance is 50-300 mu mol/g.
Further, the template substance has a metal coordinating group capable of metal chelating attachment to the surface of the fluorescent material.
Further, the metal coordinating groups include: at least one of a mercapto group-containing group, an amine group-containing group, an amide group-containing group, and an organophosphine group.
In some embodiments, the core further comprises a magnetic substance, and one template substance adsorbs or links the plurality of fluorescent materials and the plurality of magnetic substances.
In some embodiments, the fluorescent material comprises: at least one of a fluorescent nanoparticle, a fluorescent polymer, and an organic fluorescent substance, the fluorescent nanoparticle comprising one or more of a quantum dot, a metal oxide nanoparticle, a nanorod, or a nanoplatelet.
Further, the quantum dot includes: at least one of group IIB-VIA, group IIIA-VA, group IVA-VIA, group IVA, group IB-IIIA-VIA, group VIII-VIA, perovskite material and carbon quantum dots; the metal oxide comprises: zn, cr, co, dy, er, eu, fe, gd, gd, pr, nd, ni, in, pr, sm, tb, tm, and combinations thereof.
In some embodiments, in steps S2 and S3, the ligand is dissolved in the monomer, the ligand causes the modified core to be dissolved in the monomer, and the monomer forms a covalently bonded polymer shell coating the modified core by polymerization.
Further, in step S2, the ligand is added in an amount of 5 to 50wt% based on the mass of the fluorescent material in the core.
Further, when the monomer is a polymer monomer having a carbon-carbon double bond, the ligand includes a plurality of repeating units including at least one of an amine group, an epoxy group, a hydroxyl group, an amide group, a mercapto group, and a carboxyl group. Preferably, the number of repeating units is 1 to 30.
Further, the polymer monomer containing a carbon-carbon double bond includes: acrylate monomers, oligomeric acrylate monomers.
Further, when the monomer is an alkenoic silane monomer, the ligand comprises: at least one of C12-C18 alkyl polyoxyethylene acrylate group, fatty alcohol polyoxyethylene ether phosphate group, alkyl polyoxyethylene phosphate group, mercapto-polyoxyethylene sorbitan fatty acid ester group.
In some embodiments, in step S3, the fluorescent microsphere is a single organic shell layer coated fluorescent microsphere or a multi-layer organic shell layer coated fluorescent microsphere.
Further, the modified kernel, the monomer and the initiator are dispersed in an emulsifier solution, and the fluorescent microsphere coated by the single-layer organic shell layer is directly formed through polymerization reaction.
Further, preparing fluorescent seed microspheres coated with the modified inner cores in polymer microspheres, dispersing the fluorescent seed microspheres, the monomers and the initiator in an emulsifier solution, and forming the fluorescent microspheres coated with the multi-layer organic shell layer through polymerization reaction.
In some embodiments, the method further comprises step S4, wherein the fluorescent microsphere is subjected to a grafting reaction with a functional group.
Further, the functional group includes: the water-soluble functional group enables the fluorescent microsphere to have good water solubility or/and the coupling functional group enables the fluorescent microsphere to be connected with biological molecules.
In a second aspect of the present application, there is provided a fluorescent microsphere having a uniform particle size, the fluorescent microsphere comprising: a core, a ligand modifying the core, and an organic shell coating the core and the ligand; the kernel comprises: template substances and fluorescent materials, wherein the template substances are combined with the fluorescent materials, and the template substances are symmetrical substances with holes; the organic shell layer is formed by polymerization of monomers.
In some embodiments, the core comprises one template substance and a plurality of fluorescent materials, i.e., one template substance binds a plurality of fluorescent materials.
In some embodiments, the template material is a surface-modified template material having a coordinating group attached or adsorbed to the fluorescent material.
In some embodiments, the core further comprises a magnetic substance, and one template substance adsorbs or links the plurality of fluorescent materials and the plurality of magnetic substances.
In some embodiments, the ligand-modified core is referred to as a modified core, the ligand being soluble in the monomer, the ligand causing the modified core to be soluble in the monomer, the monomer forming a covalently bonded polymer shell coating the modified core by polymerization.
In a third aspect of the present application, there is provided a fluorescent microsphere having a uniform particle size, the fluorescent microsphere having a uniform particle size being obtained by the aforementioned preparation method.
In a fourth aspect of the present application, the use of the fluorescent microsphere in a biological medicine, the biological medicine comprising: drug loading, biological probes, biomarkers, disease diagnosis, tracers, solid phase chips, liquid phase chips, immunochromatography, raman scattering. The fluorescent microsphere is applied to a tracer.
Compared with the prior art, the fluorescent microsphere and the preparation method thereof have at least the following advantages:
(1) The fluorescent microsphere has uniform particle size. The particle size uniformity of the fluorescent microsphere is mainly determined by a template substance. The template substance is a symmetrical substance with a cavity, the cavity is used for containing fluorescent materials to form an inner core, and the high symmetry of the template substance makes the size of the template substance uniform; the fluorescent microsphere is formed by coating an organic shell layer on the surface of the fluorescent microsphere, and the particle size of the fluorescent microsphere is uniform.
(2) The particle size of the fluorescent microsphere is adjustable. The template substance can control the size of the template substance by controlling the length of the branched chain, so that the particle size of the fluorescent microsphere is controllable. Small particle diameter fluctuation, high precision (low PDI value, i.e. low polydispersity index).
(3) The fluorescent microsphere has good luminous performance. In the synthesis process of the fluorescent microsphere, components which cause adverse effects on the surface of the quantum dot, such as silicic acid molecules, ammonia water, ethanol and the like, cannot be generated, and the luminescent performance of the fluorescent material is good.
(4) The fluorescent microsphere has good shell tolerance of the coating shell layer and tight coating. The method carries out ligand modification on the kernel to form a modified kernel, so that the polarity of the modified kernel is similar to that of the monomer, which is the basis that the monomer cross-linked polymerization product can coat the kernel; then on the basis of the modified core, a covalently bonded polymer shell layer is formed by polymerization reaction of the monomer to cover the modified core, the covalently bonded polymer shell layer is tightly crosslinked, the fluorescent material is not easy to leak, and the water-oxygen resistance of the shell layer is good.
Drawings
The foregoing and other features of the present application will be more fully described when read in conjunction with the following drawings. It is appreciated that these drawings depict only several embodiments of the present application and are therefore not to be considered limiting of its scope. The present application will be described more specifically and in detail by using the accompanying drawings.
FIG. 1 is a schematic structural diagram of a dendritic fibrous silica.
Fig. 2 is a schematic structural diagram of a branch fibrous silica connected to a quantum dot.
FIGS. 3-1 and 3-2 are electron microscopic views of fluorescent microspheres of example 1 of the present application.
FIGS. 4-1 and 4-2 are electron microscopic views of fluorescent microspheres of example 2 of the present application.
FIG. 5 is an electron micrograph of fluorescent microspheres of example 3 of the present application.
FIG. 6 is an electron micrograph of fluorescent microspheres of a comparative example of the present application.
Detailed Description
The following examples are described to aid in the understanding of the present application and are not, nor should they be construed in any way to limit the scope of the present application.
At least one of the "when preceding or following a list of elements" as for example "is described herein modifies the entire list of elements without modifying individual elements of the list. Unless otherwise defined, all terms (including technical and scientific terms) in the specification can be defined as commonly understood by one of ordinary skill in the art. Terms defined in commonly used dictionaries should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Furthermore, unless expressly stated to the contrary, the words "comprise" and the words "comprising" when used in this specification mean the presence of stated features, regions, integers, steps, operations, elements, and/or components, but does not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof. Accordingly, the above phraseology is to be understood as meaning to include the stated elements, but not to exclude any other elements. "plurality" means two or more, and "connected" means directly or indirectly connected.
In a first aspect of the present application, a method for preparing fluorescent microspheres with uniform particle size is provided, including the steps of:
s1, combining a template substance with a fluorescent material to form an inner core, wherein the template substance is a symmetrical substance with a cavity;
s2, carrying out ligand modification on the inner core to form a modified inner core;
s3, mixing the modified kernel with a monomer, wherein the modified kernel is dissolved in the monomer; and (3) carrying out polymerization reaction on the monomer to form the fluorescent microsphere with the shell layer coating the modified core.
In some embodiments, in step S1, the core includes one template substance and a plurality of fluorescent materials, i.e., one template substance binds a plurality of fluorescent materials.
In some embodiments, in step S1, a mass ratio of template substance to fluorescent material is added of 1 (0.1-5). Preferably, in step S1, the mass ratio of the template substance to the fluorescent material is 1 (0.5-2.5).
Since the template substance has a ligand group that adsorbs or links to the fluorescent material, the added fluorescent material is able to bind to the template substance. If too little fluorescent material is added, that is, the mass ratio of the template substance to the fluorescent material is lower than 1:0.1 (the mass of the fluorescent material is lower than 10% of the mass of the template substance), the loading amount of the fluorescent material in the fluorescent microsphere is low, and the luminous intensity/brightness of the fluorescent microsphere is affected. If the fluorescent material is too much, i.e., the mass ratio of the template substance to the fluorescent material is higher than 1:5 (the mass of the fluorescent material is higher than 200% of the mass of the template substance), the ligand group of the template substance is saturated with the fluorescent material, and the rest of the fluorescent material cannot be combined with the template substance, so that the use of the fluorescent material is wasted.
In some embodiments, the template material is a rigid template material or a non-rigid template material. The template material controls the size of the template material by controlling its branch length or the volume of the shell.
In some embodiments, the rigid template material comprises: one of dendritic fibrous silica, silica having pore size, dendritic zirconium dioxide, dendritic titanium dioxide, crosslinked rigid polymer, the non-rigid template material comprising: dendritic polymers.
Wherein, the branch fibrous silica, the silica with pore diameter, the dendritic zirconium dioxide and the dendritic titanium dioxide are inorganic matters, the shapes are similar to that of dandelion, the size of the branch fibrous silica is controlled by controlling the length of a branched chain, and the structure is schematically shown in figure 1. The cross-linked rigid polymer is an organic matter, and the cross-linked rigid polymer is a hollow shell with a shape similar to a circle, and the size of the cross-linked rigid polymer is controlled by controlling the volume of the hollow shell. The dendritic polymer is an organic matter, has a dendritic shape and consists of a core and a branched chain connected with the core; the branches connecting the cores can be grown according to algebraic generation, and the length of the branches can be controlled by notifying the synthesized algebra, so that the size of the dendritic polymer can be controlled.
In some embodiments, the template material is a surface-modified template material having a coordinating group attached or adsorbed to the fluorescent material.
In some embodiments, the amount of coordinating groups on the template material is 50 to 300. Mu. Mol/g.
The template substance adsorbs or connects the fluorescent material, and the ligand group on the template substance can well connect or adsorb the fluorescent material under the content, thereby enhancing the binding property of the fluorescent material on the template substance, effectively preventing the fluorescent material from falling off, ensuring that the fluorescent material coated by the polymer shell is more stable, not easy to leak, and increasing the loading capacity of the quantum dots.
In some embodiments, the template species has a metal coordinating group capable of metal chelating attachment to the surface of the fluorescent material. The ligand group of the template substance can be modified, other types of ligand groups in the prior art can be adopted, the template substance modified by the ligand group can be adsorbed/connected with fluorescent materials, and particularly can be adsorbed/connected with quantum dots or metal oxide nanoparticles. Wherein, the structure of the branch fibrous silicon dioxide connected with the quantum dots is schematically shown in fig. 2.
In some embodiments, the metal coordinating group comprises: a sulfhydryl-containing group, an amine-containing group, an amide-containing group, an organophosphine-containing group, or any combination thereof.
In some embodiments, the thiol-containing group comprises: one of a mono-, di-or tri-mercapto group, said mercapto-containing group comprising: a mercapto-substituted ester group, a mercapto-substituted alkane group, a mercapto-substituted alkenyl group, a mercapto-substituted alkoxy group, a mercapto-substituted cycloalkyl group, a mercapto-substituted heterocycloalkyl group, a mercapto-substituted cycloalkenyl group, a mercapto-substituted heterocycloalkenyl group, a mercapto-substituted aryl group, a mercapto-substituted heteroaryl group, a mercapto-substituted aryloxy group, or a mercapto-substituted arylthio group.
In some embodiments, the core further comprises a magnetic substance, and one template substance adsorbs or links the plurality of fluorescent materials and the plurality of magnetic substances.
In some embodiments, the magnetic substance comprises: ferroferric oxide, ferric oxide, nickel oxide, cobalt oxide, magnetite, ferric oleate, ferric chloride, ferric sulfate, ferric nitrate, ferrous chloride tetrahydrate, ferric chloride hexahydrate, nickel ferrite, aluminum ferrite, manganese ferrite, zinc ferrite, cobalt ferrite, coFe 2 O 4 、NiFe 2 O 4 Or MnFe 2 O 4 One or more of the following.
In some embodiments, the particle size of the magnetic material is in the range of 5-50nm, preferably 11-30nm.
When the fluorescent microsphere contains a magnetic substance in addition to the fluorescent material, the fluorescent microsphere may also be referred to as a fluorescent magnetic microsphere. The metal coordinating group of the modified template material can also be subjected to metal chelating connection with the surface of the magnetic material.
In some embodiments, the fluorescent material comprises: at least one of a fluorescent nanoparticle, a fluorescent polymer, and an organic fluorescent substance, the fluorescent nanoparticle comprising one or more of a quantum dot, a metal oxide nanoparticle, a nanorod, or a nanoplatelet.
In some embodiments, the quantum dots comprise at least one of group IIB-VIA, group IIIA-VA, group IVA-VIA, group IVA, group IB-IIIA-VIA, group VIII-VIA, perovskite materials, and carbon quantum dots, the quantum dots have quantum confinement effects, have higher quantum yields under electrical or optical excitation, and have a narrower half-peak width of the fluorescence emission peak of the quantum dots, allowing for a wide color gamut; the light bleaching resistance is strong, the light bleaching refers to the phenomenon that the fluorescence intensity of a luminescent substance is reduced after repeated light excitation for many times, and the fluorescent quenching is not easy to happen. For example, the II-VI compound may include: cdSe, cdTe, znS, znSe, znTe, znO, hgS, hgSe, hgTe, mgSe, mgS, cdSeS, cdSeTe, cdSTe, znSeS, znSeTe, znSTe, hgSeS, hgSeTe, hgSTe, cdZnS, cdZnSe, cdZnTe, cdHgS, cdHgSe, cdHgTe, hgZnS, hgZnSe, hgZnTe, mgZnSe, mgZnS, hgZnTeS, cdZnSeS, cdZnSeTe, cdZnSTe, cdHgSeS, cdHgSeTe, cdHgSTe, hgZnSeS, hgZnSeTe, hgZnSTe or combinations thereof. The III-V compounds may include: gaN, gaP, gaAs, gaSb, alN, alP, alAs, alSb, inN, inP, inAs, inSb, gaNP, gaNAs, gaNSb, gaPAs, gaPSb, alNP, alNAs, alNSb, alPAs, alPSb, inNP, inNAs, inNSb, inPAs, inPSb, inZnP, gaAlNP, gaAlNAs, gaAlNSb, gaAlPAs, gaAlPSb, gaInNP, gaInNAs, gaInNSb, gaInPAs, gaInPSb, inAlNP, inAlNAs, inAlNSb, inAlPAs, inAlPSb or combinations thereof. The perovskite quantum dots include organic perovskite quantum dots and/or inorganic perovskite quantum dots. The particle size of the quantum dots is 1-20nm, preferably 1-10nm.
In some embodiments, the metal oxide: zn, cr, co, dy, er, eu, fe, gd, gd, pr, nd, ni, in, pr, sm, tb, tm, and combinations thereof.
In some embodiments, the organic fluorescent substance includes: fluorescein (such as FITC, RB200, TRITC and R-RE), aromatic fused ring compounds, intramolecular charge transfer compounds, metal complex fluorescent materials, enzymes and rare earth metal chelates.
The fluorescent microsphere has uniform particle size. The particle size uniformity of the fluorescent microsphere is mainly determined by a template substance. The template substance is a symmetrical substance with a cavity, the cavity is used for containing fluorescent materials to form an inner core, and the high symmetry of the template substance makes the size of the template substance uniform; the fluorescent microsphere is formed by coating the organic shell layer on the basis, and the thickness of the organic shell layer is uniform, so that the particle size of the fluorescent microsphere is also uniform. The prior art mainly starts from the process in improving the uniformity of the particle size of the fluorescent microspheres. For example, an inorganic SiO2 shell coating scheme and a polymer shell coating scheme are generated in situ, and the particle size uniformity is mainly adjusted by adjusting the system component ratio, the stirring rate and the like; according to the oil-in-water self-assembly scheme, the particle size uniformity is adjusted simply by adjusting the ultrasonic power and the time length for forming micro-droplets; emulsion polymerization high molecular polymerization microsphere scheme is difficult to control emulsion droplet size uniformity and particle size non-uniformity. The method has the effects of treating both symptoms and root causes, and the uniformity of the particle size of the fluorescent microspheres is improved, but the problem of poor repeatability of the result caused by uneven particle size of the fluorescent microspheres still exists.
The particle size of the fluorescent microsphere is adjustable. The template substance can control the size of the template substance by controlling the length of the branched chain of the template substance, and the thickness of the organic shell layer is controllable, so that the particle size of the fluorescent microsphere is controllable. Small particle diameter fluctuation, high precision (low PDI value, i.e. low polydispersity index). In the fluorescent microsphere in the prior art, the particle size is usually about 100nm, and the particle size of the fluorescent microsphere can be adjusted in a smaller range by adjusting the thickness of a shell layer or the size of micro liquid drops; or by "large spheres comprising a plurality of small spheres"/"excessively polymerized to no longer polymerize" to form micron-sized fluorescent microspheres, fluorescent microspheres with a particle size of, for example, 250nm to 700nm cannot be stably produced.
In some embodiments, in steps S2 and S3, the ligand is dissolved in the monomer, the ligand causes the modified core to be dissolved in the monomer, and the monomer forms a covalently bonded polymer shell coating the modified core by polymerization.
In some embodiments, when the monomer is a polymer monomer containing a carbon-carbon double bond, the ligand comprises a plurality of repeating units comprising at least one of an amine group, an epoxy group, a hydroxyl group, an amide group, a mercapto group, a carboxyl group. Preferably, the number of repeating units is 1 to 30.
In some embodiments, the polymer monomer containing a carbon-carbon double bond comprises: acrylate monomers, oligomeric acrylate monomers. The ligand comprises: thiol tween 80, polyether amine M-1000, alkylphenol polyoxyethylene ether phosphate group, phosphoric JTM9601, carboxyl tween 80 and polyether organosilicon copolymer.
In some embodiments, the acrylate monomer comprises: monofunctional (meth) acrylates, difunctional (meth) acrylates, trifunctional (meth) acrylates, oligomeric acrylate monomers include: at least one of polyester acrylic ester and polyurethane acrylic ester, and the molecular weight of the oligomer acrylic ester monomer is 300-3000.
In some embodiments, the monofunctional (meth) acrylate comprises: styrene, methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, hexyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, undecyl (meth) acrylate, dodecyl (meth) acrylate, cyclohexyl (meth) acrylate, dicyclopentyl (meth) acrylate, lauryl (meth) acrylate, benzyl (meth) acrylate or phenyl (meth) acrylate, dicyclopentanyl (meth) acrylate (HDCPMA), cyclohexyl (meth) acrylate, 4-t-butylcyclohexyl (meth) acrylate, 3, 5-trimethylcyclohexyl (meth) acrylate, isobornyl (meth) acrylate, 1-adamantane (meth) acrylate (AMA), 2-adamantane (meth) acrylate, isooctyl (meth) acrylate, isononyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, lauric (meth) acrylate (LMA), stearic (meth) acrylate.
In some embodiments, the difunctional (meth) acrylate includes: tripropylene glycol di (meth) acrylate, tetraethylene glycol dimethacrylate, 1, 12-dodecanediol ester, 1, 10-decanediol dimethacrylate, tricyclo [5.2.1.02,6] decanedimethanol acrylate or 1, 6-hexanediol diacrylate.
In some embodiments, the trifunctional (meth) acrylate includes: one or more of (ethoxylated) trimethylolpropane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, dipentaerythritol tri (meth) acrylate and the like.
In some embodiments, the polymer monomer containing a carbon-carbon double bond further comprises: styrene, vinyl chloride, divinylbenzene, allyl ether, diethyl diallyldioate, diallyl disulfide.
In some embodiments, the monomer is an alkenoic silane monomer (polymerization reaction) and the ligand comprises: at least one of C12-C18 alkyl polyoxyethylene acrylate group, fatty alcohol polyoxyethylene ether phosphate group, alkyl polyoxyethylene phosphate group, mercapto-polyoxyethylene sorbitan fatty acid ester group.
The olefinic silane monomer includes: at least one of triethoxysiloxane acrylate, triethoxysilane propyl methacrylate, tripropoxysilane methacrylate, 3-propyltris (trimethoxy silicon) methacrylate, and propoxytriacetoxy silane methacrylate.
In some embodiments, in step S3, the fluorescent microsphere is a single organic shell layer coated fluorescent microsphere or a multi-layer organic shell layer coated fluorescent microsphere.
In some embodiments, the modified core, the monomer, and the initiator are dispersed in an emulsifier solution to directly form the monolayer organic shell coated fluorescent microsphere by polymerization.
For example, dispersing the modified core in an acrylate monomer, adding a solvent such as n-hexadecane, and mixing with an emulsifier solution; and adding an initiator, and stirring to directly form the fluorescent microsphere coated by the single-layer organic shell layer.
In some embodiments, fluorescent seed microspheres are prepared in which the modified inner core is encapsulated within polymeric microspheres, the fluorescent seed microspheres, the monomer, and an initiator are dispersed in an emulsifier solution, and the multilayer organic shell-encapsulated fluorescent microspheres are formed by polymerization.
For example, the surface of the fluorescent seed microsphere contains binding sites such as carbon-carbon double bonds, sulfhydryl groups and the like, and the monomer and the binding sites on the surface of the fluorescent seed microsphere undergo a cross-linking polymerization reaction under the action of an initiator to form a covalently bonded polymer shell layer, so that the fluorescent seed microsphere is coated with a double-layer organic shell layer.
In some embodiments, the initiator comprises: at least one of potassium persulfate, ammonium persulfate, azobisisobutylamidine hydrochloride, azobisiso Ding Mi hydrochloride, and azobisisopropyl imidazoline.
In some embodiments, the emulsifier comprises: at least one of polyacrylic acid, sodium oleate, sodium dodecyl sulfonate, polyethylene glycols, polyvinyl alcohols and polyvinylpyrrolidone.
In some embodiments, the method further comprises step S4, wherein the fluorescent microsphere is subjected to a grafting reaction with a functional group.
In some embodiments, the functional group comprises: the water-soluble functional group enables the fluorescent microsphere to have good water solubility or/and the coupling functional group enables the fluorescent microsphere to be connected with biological molecules.
In some embodiments, the water-soluble functional group comprises: carboxyl and hydroxyl. The component containing the water-soluble functional group comprises: at least one of acrylic acid, methacrylic acid, polyacrylic acid, polymethacrylic acid, itaconic acid and maleic acid.
In some embodiments, the coupling functional group comprises: amino, epoxy, azido, aldehyde. The component containing the coupling functional group includes: at least one of glycidyl methacrylate, allyl glycidyl ether, epoxy polyethylene glycol acrylate, epoxy polyethylene glycol methacrylate, azido polyethylene glycol acrylate, azido polyethylene glycol methacrylate, aldehyde polyethylene glycol acrylate, aldehyde polyethylene glycol methacrylate, disodium 4,4 '-diazidostilbene-2, 2' -disulfonate tetrahydrate, acrolein, trans-2-pentenal, 3- (2-furyl) acrolein, 3-dimethylaminoacrolein, 2-methacrolein, and cinnamaldehyde.
In some embodiments, the particle size of the fluorescent microsphere is 200-700nm and the particle size of the inner core of the fluorescent microsphere is 140-600nm.
The fluorescent microsphere has good luminous performance. In the synthesis process of the fluorescent microsphere, components which cause adverse effects on the surface of the quantum dot, such as silicic acid molecules, ammonia water, ethanol and the like, cannot be generated, and the luminescent performance of the fluorescent material is good. In the prior art, for example, in situ generation inorganic SiO2 shell coating technology, a mesoporous SiO2 shell is formed by hydrolyzing silicon sources such as ethyl orthosilicate, methyl orthosilicate, butyl orthosilicate, methyltrimethoxysilane or methyltriethoxysilane, and the like, so that the fluorescent material is coated in the mesoporous SiO2 shell. Silicic acid molecules, ammonia water, ethanol and the like during the hydrolysis of a silicon source can cause adverse effects on the surface of the quantum dot, and cause the falling of ligands, thereby causing fluorescence quenching.
The fluorescent microsphere has good shell tolerance of the coating shell layer and tight coating. The method carries out ligand modification on the kernel to form a modified kernel, so that the polarity of the modified kernel is similar to that of the monomer, which is the basis that the monomer cross-linked polymerization product can coat the kernel; then on the basis of the modified core, a covalently bonded polymer shell layer is formed by polymerization reaction of the monomer to cover the modified core, the covalently bonded polymer shell layer is tightly crosslinked, the fluorescent material is not easy to leak, and the water-oxygen resistance of the shell layer is good. In the prior art, such as an in-situ generation inorganic SiO2 shell coating technology, the inorganic SiO2 shell has poor water resistance and is easy to permeate. For example, in the oil-in-water self-assembly scheme, the self-assembly depends on physical combination of adsorption and long-chain winding of amphiphilic polymers such as PMAO, the wrapping layer is not tight, and the quantum dots are easy to leak; and the PMAO and other substances do not contain polymerizable bonds such as double bonds, and can not be polymerized to form a second coating layer.
In addition, the prior art polymer shell coating scheme is that firstly, the emulsion droplet size is difficult to control, the particle size of the synthesized fluorescent microsphere is not uniform, and the adjustable range of the particle size of the fluorescent microsphere is small. Secondly, the technical scheme of polymer shell formation is that (1) quantum dots and monomers are mixed to form seed microspheres; the seed microsphere, monomer and initiator are then mixed to form a covalently bonded polymer shell. (2) And mixing the quantum dots, the monomer and the initiator to directly form a covalently bonded polymer shell. However, the core containing the template substance is provided with the template substance, and the technical scheme of forming the polymer shell layer in the prior art is adopted, so that the shell layer cannot grow on the core, or the shell layer cannot grow well and cannot be uniformly coated on the core. Only by adopting the technical scheme of the application, the template substance is firstly connected with/adsorbed on the fluorescent material to form the inner core, then the inner core is subjected to ligand modification to form a modified inner core, and the ligand modification enables the polarity of the modified inner core to be similar to that of the monomer, so that the base that the monomer crosslinked polymerization product can be coated on the inner core; based on the above, the polymer generated by the polymerization reaction of the monomer can completely and uniformly coat the modified core to form a compact polymer shell.
In a second aspect of the present application, there is provided a fluorescent microsphere having a uniform particle size, the fluorescent microsphere comprising: a core, a ligand modifying the core, and an organic shell coating the core and the ligand; the kernel comprises: template substances and fluorescent materials, wherein the template substances are combined with the fluorescent materials, and the template substances are symmetrical substances with holes; the organic shell layer is formed by polymerization of monomers.
In some embodiments, the core comprises one template substance and a plurality of fluorescent materials, i.e., one template substance binds a plurality of fluorescent materials.
In some embodiments, the template material is a surface-modified template material having a coordinating group attached or adsorbed to the fluorescent material.
In some embodiments, the core further comprises a magnetic substance, and one template substance adsorbs or links the plurality of fluorescent materials and the plurality of magnetic substances.
In some embodiments, the ligand-modified core is referred to as a modified core, the ligand being soluble in the monomer, the ligand causing the modified core to be soluble in the monomer, the monomer forming a covalently bonded polymer shell coating the modified core by polymerization.
In a third aspect of the present application, there is provided a fluorescent microsphere having a uniform particle size, the fluorescent microsphere having a uniform particle size being obtained by the aforementioned preparation method.
In a fourth aspect of the present application, the use of the fluorescent microsphere in a biological medicine, the biological medicine comprising: drug loading, biological probes, biomarkers, disease diagnosis, tracers, solid phase chips, liquid phase chips, immunochromatography, raman scattering. The fluorescent microsphere is applied to tracers, such as groundwater tracers, petroleum tracers, gas phase tracers and the like.
The present invention will be described in further detail with reference to specific examples and comparative examples, but the present invention is not limited to the following examples, and the implementation conditions adopted in the examples may be further adjusted according to different requirements of specific use, and the conditions not specified are conventional conditions in the industry.
Example 1:
and S1, obtaining a kernel. 200mg of mercaptopropyl trimethoxysilane modified dendritic fibrous silica with the particle size of 200nm and 200mg of CdSe quantum dots (with oleic acid and oleylamine) are taken and dissolved in 10ml of chloroform. And (3) dissolving in ultrasonic for 30min, wherein branch fibrous silicon dioxide is connected with CdSe quantum dots to obtain the inner core.
Step S2: obtaining the modified kernel. And (3) adding 40ul of polyetheramine M-1000 ligand into the S1 solution, stirring for 12 hours at room temperature, and centrifuging to obtain a modified kernel.
Step S3: obtaining seed microspheres.
And (3) redissolving the modified kernel obtained in the step (S2) in 10ml of chloroform, adding 0.4ml of IBOMA (isobornyl methacrylate) and 2ul of n-hexadecane, adding into 50ml of SDS (sodium dodecyl sulfate) aqueous solution with the concentration of 2mg/ml, stirring for 15min, and performing ultrasonic treatment on the mixture for 15min (power of 75W) by a probe to obtain micro-droplets. Heating to 70 ℃, stirring for 2 hours, and removing chloroform to obtain seed microspheres. Adding sodium bicarbonate to adjust pH to 7.5, and charging nitrogen for protection.
Step S4: obtaining the fluorescent microsphere.
Preparing a monomer solvent: 0.5ml of HDDA (hexanediol dimethacrylate), 120ul of TMPTA (ethoxylated trimethylolpropane triacrylate) and 5ul of n-hexadecane were mixed. 10ml of SDS aqueous solution with the concentration of 1mg/ml is added into the monomer solution, the ultrasonic power is 500W, and the emulsion is carried out for 15min. Preparing an initiator solvent: 30mg kps (potassium persulfate) was added to 6ml of deionized water. And (3) respectively and simultaneously adding the emulsified monomer solution and the initiator solvent into the step (S3) dropwise at the speed of 2 ml/hour to obtain the fluorescent microsphere.
Step S5: the fluorescent microsphere is grafted with a functional group. In S4, 200ul of Acrylic Acid (AA) was added, and the reaction was stirred for 2 hours. Centrifuging, precipitating, and then re-dissolving and washing for 3 times by using deionized water to obtain the fluorescent microsphere with the surface carboxyl modified.
The fluorescent microspheres prepared in example 1 were subjected To Electron Microscopy (TEM) and electron microscopy (SEM) as shown in FIG. 3-1 and FIG. 3-2.
The fluorescent microspheres prepared in example 1 were measured to have an average particle size of 248 nm and a PDI (polydispersity index) value of 0.023 using a nano-sized Zeta potentiometer.
The fluorescent microspheres prepared in example 1 were diluted 100 times and spotted on NC film, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 123752nits.
Ageing experiments
An aging test was performed on the fluorescent microspheres obtained in example 1. The fluorescent microspheres obtained in example 1 were placed in an atmosphere of 90% RH at 60℃for 3 hours.
The sample was spotted onto NC film after 100-fold dilution, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 99372nits.
Example 2:
and S1, obtaining a kernel. 200mg of dendrobe fibrous silicon dioxide with particle size of 260nm modified by mercaptopropyl trimethoxy silane and 200mg of CdSe quantum dots (with oleic acid and oleylamine) are taken and dissolved in 10ml of chloroform. And (5) carrying out ultrasonic treatment for 30min to dissolve to obtain branch fibrous silicon dioxide connected with CdSe quantum dots, and obtaining the inner core.
Step S2: obtaining the modified kernel. And (3) adding 40ul of sulfhydryl Tween 80 ligand into the S1 solution, stirring at room temperature for 12h, and centrifuging to obtain the modified kernel.
Step S3: obtaining seed microspheres.
And (3) redissolving the modified kernel obtained in the step (S2) in 10ml of chloroform, adding 0.4ml of HDDA (hexanediol dimethacrylate) and 5ul of n-hexadecane, adding into 50ml of SDS (sodium dodecyl sulfate) aqueous solution with the concentration of 2mg/ml, stirring for 20min, and performing ultrasonic treatment on the probe for 15min (power of 75W) to obtain micro-droplets. Heating to 70 ℃, stirring for 2 hours, and removing chloroform to obtain seed microspheres. Adding sodium bicarbonate to adjust pH to 7.0, and charging nitrogen for protection.
Step S4: obtaining the fluorescent microsphere.
Preparing a monomer solvent: 1ml of styrene, 0.2ml of divinylbenzene, 30ul of HDDA (hexanediol dimethacrylate) and 5ul of n-hexadecane were mixed. 10ml of SDS aqueous solution with the concentration of 1mg/ml is added into the monomer solution, and the ultrasonic power is 400W, so that the emulsion is carried out for 20min. Preparing an initiator solvent: 30mg kps (potassium persulfate) was added to 6ml of deionized water. And (3) respectively and simultaneously adding the emulsified monomer solution and the initiator solution into the step (S3) dropwise at the speed of 2 ml/hour to obtain the fluorescent microsphere.
Step S5: the fluorescent microsphere is grafted with a functional group. In S4, 200ul of Acrylic Acid (AA) was added, and the reaction was stirred for 2 hours. Centrifuging, precipitating, and then re-dissolving and washing for 3 times by using deionized water to obtain the fluorescent microsphere with the surface carboxyl modified.
The fluorescent microspheres prepared in example 2 were subjected To Electron Microscopy (TEM) and electron microscopy (SEM) as shown in FIG. 4-1 and FIG. 4-2.
The fluorescent microspheres prepared in example 2 were measured to have an average particle size of 314nm and a PDI (polydispersity index) value of 0.029 using a nano-sized Zeta potentiometer.
The fluorescent microspheres prepared in example 2 were diluted 100 times and spotted on NC film, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 117841nits.
Ageing experiments
An aging test was performed on the fluorescent microspheres obtained in example 2. The fluorescent microspheres obtained in example 2 were placed in an atmosphere of 90% RH at 60℃for 3 hours.
The sample was spotted onto NC film after 100-fold dilution, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 95451nits.
Example 3:
and S1, obtaining a kernel. 200mg of mercaptopropyl trimethoxysilane modified dendritic fibrous silica with the particle size of 200nm and 200mg of CdSe quantum dots (with oleic acid and oleylamine) are taken and dissolved in 10ml of chloroform. And (3) dissolving in ultrasonic for 30min, wherein branch fibrous silicon dioxide is connected with CdSe quantum dots to obtain the inner core.
Step S2: obtaining the modified kernel. And (3) adding 40ul of polyetheramine M-1000 ligand into the S1 solution, stirring for 12 hours at room temperature, and centrifuging to obtain a modified kernel.
Step S3: obtaining the fluorescent microsphere.
The modified core obtained in the step S2 is redissolved in 10ml of chloroform, 1ml of styrene and 20ul of n-hexadecane are added, and then the mixture is added into 50ml of SDS (sodium dodecyl sulfate) aqueous solution with the concentration of 2mg/ml, and the mixture is stirred for 20min. 30mg kps (potassium persulfate) was added to the reaction system and stirred for 4 hours. Obtaining the fluorescent microsphere coated by the single-layer polymer shell.
Step S4: the fluorescent microsphere is grafted with a functional group. In S3, 200ul of Acrylic Acid (AA) was added, and the reaction was stirred for 2 hours. Centrifuging, precipitating, and then re-dissolving and washing for 3 times by using deionized water to obtain the fluorescent microsphere with the surface carboxyl modified.
The fluorescent microspheres prepared in example 3 were subjected To Electron Microscopy (TEM) using a field emission transmission electron microscope (sem), and an electron micrograph thereof was taken as shown in fig. 5.
The fluorescent microspheres prepared in example 3 have an average particle size of 231nm and a PDI (polydispersity index) value of 0.026 as measured by a nano-particle size Zeta potentiometer.
The fluorescent microspheres prepared in example 1 were diluted 100 times and spotted on NC film, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 114388nits.
Ageing experiments
An aging test was performed on the fluorescent microspheres obtained in example 1. The fluorescent microspheres obtained in example 1 were placed in an atmosphere of 90% RH at 60℃for 3 hours.
The sample was spotted onto NC film after 100-fold dilution, and the fluorescent brightness was measured by a dry fluorescent analyzer to be 79372nits.
As can be seen from the electron microscope images of the examples 1-3, the fluorescent microsphere has excellent formation, uniform cladding, good dispersibility and no adhesion phenomenon.
Meanwhile, the PDI value of the fluorescent microsphere of example 1 was 0.023, the PDI value of example 2 was 0.029, and the PDI value of the fluorescent microsphere of example 3 was 0.026. The PDI value of the fluorescent microsphere has huge difference with the prior art, which shows that the particle size of the fluorescent microsphere is uniform and is obviously superior to the prior art. Template substances such as dendritic fibrous silica can be prepared to have standard particle sizes, and the thickness of the bilayer/monolayer polymer coated shell layer is controllable (e.g., controlling the mass ratio of added components, reaction time, etc.), so that the particle size of the synthesized fluorescent microspheres is controllable. This point can also be confirmed from examples, both examples 1 and 2 are double-layer polymer coated, the particle size of the template material of example 1 is 200nm, the particle size of the prepared fluorescent microsphere is 246nm, and the particle size of the fluorescent microsphere is greater than the particle size of the template material by about 40nm; the template material of example 2 had a particle size of 260nm, and the prepared fluorescent microspheres had a particle size of 314nm, which was about 40nm larger than the template material. Namely, the fluorescent microsphere has uniform particle size, and can be synthesized into the fluorescent microsphere with various particle size specifications.
In addition, the fluorescent microsphere polymer shell layer is tightly coated and has good shell resistance. Example 1 after the aging test, the brightness of the fluorescent microspheres was reduced by 19.7%; example 2 the brightness of the fluorescent microspheres was reduced by 19.0% after the aging test; example 3 after the aging test, the brightness of the fluorescent microspheres was reduced by 30.6%. Whereas the prior art PS cladding, self-assembled PMAO cladding, silica cladding, etc., the brightness of the fluorescent microspheres was reduced by more than 60% (some even up to 80%). Comparative example 1:
and S1, obtaining a kernel. 200mg of mercaptopropyl trimethoxysilane modified dendritic fibrous silica with the particle size of 200nm and 200mg of CdSe quantum dots (with oleic acid and oleylamine) are taken and dissolved in 10ml of chloroform. And (3) dissolving in ultrasonic for 30min, wherein branch fibrous silicon dioxide is connected with CdSe quantum dots to obtain the inner core.
Step S2: the inner core obtained in the step S1 is redissolved in 10ml of chloroform, 0.4ml of IBOMA (isobornyl methacrylate) and 2ul of n-hexadecane are added, then the mixture is added into 50ml of SDS (sodium dodecyl sulfate) water solution with the concentration of 2mg/ml, stirring is carried out for 15min, and the probe is used for ultrasonic treatment for 15min (power of 75W) to obtain micro liquid drops. The temperature was raised to 70℃and stirred for 2 hours to remove chloroform. Adding sodium bicarbonate to adjust pH to 7.5, and charging nitrogen for protection.
Step S3: preparing a monomer solvent: 0.5ml of HDDA (hexanediol dimethacrylate), 120ul of TMPTA (ethoxylated trimethylolpropane triacrylate) and 5ul of n-hexadecane were mixed. 10ml of SDS aqueous solution with the concentration of 1mg/ml is added into the monomer solution, the ultrasonic power is 500W, and the emulsion is carried out for 15min. Preparing an initiator solvent: 30mg kps (potassium persulfate) was added to 6ml of deionized water. The emulsified monomer solution and the initiator solvent were simultaneously added dropwise to step S2 at a rate of 2 ml/hr, respectively.
Step S4: in S3, 200ul of Acrylic Acid (AA) was added, and the reaction was stirred for 2 hours. Centrifuging, precipitating, and then re-dissolving and washing 3 times by using deionized water.
The fluorescent microspheres prepared in the comparative example were subjected To Electron Microscopy (TEM) using a field emission transmission electron microscope (sem), and an electron micrograph thereof was taken, as shown in fig. 6.
The polarity of the inner core which is not subjected to ligand modification is too different from that of the acrylic acid monomer, the emulsified IBOMA cannot be uniformly covered on the seed balls, the inner core can be separated after chloroform is evaporated, SDS is coated to form monomer pellets, when a shell monomer is dripped (step S3), the growth site of the inner core is coated by SDS to form monomer pellets, the inner core cannot be successfully coated with a polymer shell layer, and no obvious shell layer is arranged on the surface of the inner core in an electron microscope image.
While various aspects and embodiments have been disclosed, other aspects and embodiments will be apparent to those skilled in the art, and many changes and modifications can be made without departing from the spirit of the application, which is intended to be within the scope of the invention. The various aspects and embodiments disclosed herein are for illustration only and are not intended to limit the application, the actual scope of which is subject to the claims.
Claims (10)
1. The preparation method of the fluorescent microsphere with uniform particle size is characterized by comprising the following steps:
s1, combining a template substance with a fluorescent material to form an inner core, wherein the template substance is a symmetrical substance with a cavity;
s2, carrying out ligand modification on the inner core to form a modified inner core;
s3, mixing the modified kernel with a monomer, wherein the modified kernel is dissolved in the monomer; and (3) carrying out polymerization reaction on the monomer to form the fluorescent microsphere with the shell layer coating the modified core.
2. The method of preparing fluorescent microspheres with uniform particle size according to claim 1, wherein the core comprises a template material and a plurality of fluorescent materials in step S1.
3. The method of preparing uniform particle size fluorescent microspheres of claim 1, comprising one or more features selected from the group consisting of:
(1) The template substance is a rigid template substance or a non-rigid template substance;
preferably, in step S1, the mass ratio of the template substance to the fluorescent material is 1 (0.1-5);
(2) The template substance is a surface-modified template substance, and the template substance is provided with a coordination group connected or adsorbed with the fluorescent material;
preferably, the template substance has a metal coordinating group capable of metal chelating connection with the surface of the fluorescent material; the metal coordinating groups include: at least one of a mercapto group-containing group, an amine group-containing group, an amide group-containing group, and an organophosphine group;
preferably, the content of coordinating groups on the template substance is 50-300 mu mol/g;
(3) The inner core further comprises magnetic substances, and one template substance adsorbs or connects a plurality of fluorescent materials and a plurality of magnetic substances;
(4) The fluorescent material comprises: at least one of a fluorescent nanoparticle, a fluorescent polymer, and an organic fluorescent substance, the fluorescent nanoparticle comprising one or more of a quantum dot, a metal oxide nanoparticle, a nanorod, or a nanoplatelet.
4. The method of preparing fluorescent microspheres with uniform particle size according to claim 1, wherein in steps S2 and S3, the ligand is dissolved in the monomer, the ligand makes the modified core dissolved in the monomer, and the monomer forms a covalently bonded polymer shell layer to encapsulate the modified core through polymerization.
5. The method of preparing uniform particle size fluorescent microspheres of claim 4, comprising one or more features selected from the group consisting of:
(1) When the monomer is a polymer monomer containing a carbon-carbon double bond, the ligand comprises a plurality of repeating units, and the repeating units comprise at least one of an amine group, an epoxy group, a hydroxyl group, an amide group, a sulfhydryl group and a carboxyl group;
(2) When the monomer is an alkenoic silane monomer, the ligand comprises: at least one of C12-C18 alkyl polyoxyethylene acrylate group, fatty alcohol polyoxyethylene ether phosphate group, alkyl polyoxyethylene phosphate group, mercapto-polyoxyethylene sorbitan fatty acid ester group;
(3) In step S2, the mass of the ligand added accounts for 5-50wt% of the mass of the fluorescent material in the core.
6. The method of producing fluorescent microspheres with uniform particle size according to claim 1, wherein in step S3, the fluorescent microspheres are single-layered organic shell-coated fluorescent microspheres or multi-layered organic shell-coated fluorescent microspheres.
7. The method for preparing fluorescent microspheres with uniform particle size according to claim 6, wherein the modified core, the monomer and the initiator are dispersed in an emulsifier solution, and the fluorescent microspheres coated with the single organic shell layer are directly formed through polymerization reaction; or preparing fluorescent seed microspheres coated with the modified inner cores in polymer microspheres, dispersing the fluorescent seed microspheres, the monomer and the initiator in an emulsifier solution, and forming the fluorescent microspheres coated with the multi-layer organic shell layer through polymerization reaction.
8. The method for preparing fluorescent microspheres with uniform particle size according to claim 1, further comprising step S4 of grafting the fluorescent microspheres with functional groups.
Preferably, the functional group includes: the water-soluble functional group enables the fluorescent microsphere to have good water solubility or/and the coupling functional group enables the fluorescent microsphere to be connected with biological molecules.
9. A fluorescent microsphere having a uniform particle size, the fluorescent microsphere comprising: a core, a ligand modifying the core, and an organic shell coating the core and the ligand; the kernel comprises: template substances and fluorescent materials, wherein the template substances are combined with the fluorescent materials, and the template substances are symmetrical substances with holes; the organic shell layer is formed by polymerization reaction of monomers;
preferably, the core comprises a template substance and a plurality of fluorescent materials, i.e. a template substance binds a plurality of fluorescent materials;
preferably, the template substance is a surface-modified template substance, and the template substance has a ligand group connected or adsorbed with the fluorescent material;
preferably, the inner core further comprises a magnetic substance, and one template substance adsorbs or connects a plurality of fluorescent materials and a plurality of magnetic substances;
Preferably, the ligand-modified core is referred to as a modified core, the ligand being soluble in the monomer, the ligand causing the modified core to be soluble in the monomer, the monomer forming a covalently bonded polymer shell coating the modified core by polymerization.
10. Fluorescent microsphere with uniform particle size, characterized in that the fluorescent microsphere with uniform particle size is obtained by the preparation method according to any one of claims 1-8.
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