KR102484477B1 - Magnetic-Optical Composite Nanoparticles - Google Patents

Abstract

The present invention relates to magnetic-optical composite structure nanoparticles.
In the present invention, magnetic-optical composite structure nanoparticles composed of quantum dots having fluorescence signals, noble metal nanoparticles having metal-enhanced fluorescence (MEF) characteristics, and magnetic nanoparticles overcome fluorescence signal suppression and improve biomolecule or biomaterial detection ability can be provided.

Description

Magnetic-optical composite structure nanoparticles {Magnetic-Optical Composite Nanoparticles}

The present invention relates to a magnetic-optical composite structure nanoparticle composed of magnetic nanoparticles and heterogeneous nanoparticles capable of simultaneously realizing magnetic and optical functions, a manufacturing method thereof, and detection of a specific material using the same.

More specifically, it provides a platform for manufacturing magnetic-optical composite nanoparticles of various configurations, magnetic separation using the magnetic properties of the magnetic-optical composite nanoparticles, and metal reinforcement between noble metal nanoparticles and quantum dot nanoparticles. It relates to optical performance improvement using fluorescence (MEF) phenomenon and a method for manufacturing a probe for biomolecule detection.

Enzyme-Linked Immunosorbent Assay (ELISA) and flow cytometry are used as existing in vitro diagnostic biomolecule detection methods, but these are imported products and have the disadvantage of high cost and time consuming. In addition, the organic phosphor has a high possibility of error in inspection in terms of a short life time and poor stability.

In order to solve this problem, nanomaterials with high detection sensitivity have recently been used from various perspectives. Upconversion nanoparticles and quantum dots are being used, but since they do not have magnetic properties, molecules or proteins to be captured cannot be separated independently. Therefore, there are disadvantages in that a bead having magnetic properties must be used, and a process for extracting specific molecules and proteins to be captured is complicated.

Although magnetic-optical nanoparticles in which metals and metal oxides have been suggested as alternatives are expected to have great applicability, it is difficult to have uniform magnetic and optical properties within a single nanoparticle at the same time, and magnetic nanoparticles The application is limited in that the particles cause quenching of the light emitting nanostructure.

In the present invention, magnetic nanoparticles and noble metal nanoparticles are chemically bonded to the surface of the first ceramic core-shell nanoparticle, and then a second ceramic shell is formed and quantum dot nanoparticles are chemically bonded thereon to produce magnetic-optical complex functional nanoparticles. provides a way to In addition, the luminescence efficiency of quantum dots is improved by using metal-enhanced fluorescence (MEF) of the magnetic-optical composite functional nanoparticles, and target cells are imaged using the improved luminescence signal. In addition, the biomaterial is quantitatively analyzed using the magnetic-optical complex functional nanoparticles and detected through a colorimetric assay.

1. Korean Patent Publication No. 10-1304427

An object of the present invention is to provide magnetic-optical complex structured nanoparticles composed of quantum dot nanoparticles, noble metal nanoparticles, and magnetic nanoparticles having a fluorescence signal, and a manufacturing method thereof.

In addition, an object of the present invention is to overcome suppression of a light emitting signal of quantum dot nanoparticles by magnetic nanoparticles using the magnetic-optical composite structure nanoparticles and to provide biomolecule or biomaterial detection capabilities.

The present invention comprises the steps of preparing core-shell nanoparticles by forming a first ceramic shell on magnetic nanoparticles;

attaching noble metal nanoparticles to the surface of the first shell of the core-shell nanoparticles to produce core-shell nanoparticles to which noble metal nanoparticles are attached;

preparing a core-double shell nanoparticle by forming a second ceramic shell surrounding the core-shell nanoparticle to which the noble metal nanoparticle is attached; and

It provides a method for producing a magnetic-optical composite structure nanoparticle comprising the step of preparing a magnetic-optical composite structure nanoparticle by attaching quantum dot nanoparticles to the surface of the second shell of the core-double shell nanoparticle.

In addition, the present invention is produced by the above-described manufacturing method,

Core-shell nanoparticles including a magnetic nanoparticle core and a first ceramic shell;

noble metal nanoparticles formed on the surface of the first ceramic shell of the core-shell nanoparticles;

a second ceramic shell surrounding the core-shell nanoparticles on which the noble metal nanoparticles are formed; and

A magnetic-optical composite structure nanoparticle including quantum dot nanoparticles formed on the surface of the second ceramic shell is provided.

In addition, the present invention provides a composition for diagnostic imaging, a kit for detecting an analyte, or a molecular diagnostic chip including the magnetic-optical complex structure nanoparticles.

In addition, the present invention includes the steps of functionalizing a biomolecule capable of binding to an analyte to be detected on the surface of the above-described magnetic-optical composite structure nanoparticle;

exposing the functionalized magnetic-optical composite nanoparticles to a sample containing one or more analytes; and

A method for imaging or detecting an analyte comprising the step of identifying an analyte bound to the magnetic-optical composite structure nanoparticles using photoluminescence spectroscopy is provided.

In the present invention, magnetic-optical composite structure nanoparticles composed of magnetic nanoparticles, noble metal nanoparticles, and quantum dot nanoparticles are used to specifically capture and detect biomolecules or biomaterials, as well as colorimetric analysis and luminescence. Quantitative analysis can be performed using the signal.

Therefore, the magnetic-optical composite structure nanoparticles of the present invention can be used in various biomedical fields such as disease diagnosis, cell separation, and imaging.

In Figure 1 (a) is a schematic diagram of the manufacturing process of magnetic-optical composite nanoparticles composed of iron oxide nanoparticles, gold nanoparticles, and cadmium selenide quantum dot nanoparticles having amplified light emitting signals of quantum dots, and the nanoparticles produced in each process. A transmission electron microscopy (TEM) picture of the particle is shown.
In FIG. 1, (b) shows a strategy for amplifying the intensity of fluorescence signals using MEF by plasmonic nanoparticles such as noble metal nanoparticles, and fluorescence signal intensity by adjusting the distance between noble metal nanoparticles and quantum dot nanoparticles in the process. It is a schematic diagram showing the process of maximizing the amplification of .
In FIG. 2 (a) is a schematic diagram and transmission electron micrograph showing the thickness change of the second silica shell according to the amount of the silica precursor.
In Figure 2 (b) is a graph showing the results of measuring the thickness of the second silica shell of the magnetic-optical composite structure nanoparticles prepared in Example.
In FIG. 3, (a) is a transmission electron micrograph of manganese-doped zinc sulfide quantum dots and cadmium selenide quantum dots, a transmission electron micrograph of the magnetic-optical composite structure nanoparticles prepared in Example, and a photoluminescence (PL) photoluminescence spectrometer (PL). ) represents the fluorescence signal identified by.
In FIG. 3 (b) shows a transmission electron microscope image and an energy dispersive spectroscopy (EDS) image of the magnetic-optical composite structure nanoparticles prepared in Example.
In Figure 4 (a) is a schematic diagram and transmittance of the magnetic-optical nanoparticles (Bare without Au) prepared in Comparative Example and the magnetic-optical composite structure nanoparticles (having a difference in the thickness of the second ceramic shell) prepared in Examples Shows electron micrographs.
In FIG. 4 (b), in order to confirm the increase in the size of the nanoparticles according to the thickness of the second silica shell of the magnetic-optical composite structure nanoparticles prepared in Example, measured by Dynamic Light Scattering (DLS) It shows the microfluidic size (result of change in particle size distribution), and (c) shows the result of measuring the change in PL intensity according to the thickness of the second silica shell by photoluminescence spectroscopy of a fluorescence microscope.
In FIG. 5 (a) is a schematic diagram showing a process of specifically detecting and imaging cancer cells with magnetic-optical composite structure nanoparticles to which cyclic arginine-glycine-aspartic acid tripeptide (cRGD) is attached.
In FIG. 5 (b), brain tumor cells (U87MG cells) and breast cancer cells (MCF7 cells) were examined under a fluorescence microscope using magnetic-optical composite structure nanoparticles to which cyclic arginine-glycine-aspartic acid tripeptide (cRGD) is attached. shows the results of imaging. At this time, brain tumor cells have a high level of expression of cRGD-coupled receptors (integrin) on the cell surface, and breast cancer cells have a low level of expression of the integrin on the surface.
In FIG. 6, (a) is a schematic diagram showing the process of modifying antibodies to magnetic-optical composite structure nanoparticles, magnetically separating the resulting antigen, and detecting fluorescence, and (b) is a magnetic-optical composite in which influenza A antibody is surface-functionalized. The result of confirming the intensity of the luminescence signal at the same time as the immunochromatography rapid test (colorimetric analysis) according to the influenza A virus concentration using the structural nanoparticles is shown.

Hereinafter, the present invention will be described in detail.

The present invention relates to a method for producing magnetic-optical composite structure nanoparticles, in which magnetic-optical composite structure nanoparticles according to the present invention (A) form a first ceramic shell on magnetic nanoparticles to prepare core-shell nanoparticles. Step of doing (hereinafter, core-shell nanoparticle preparation step);

(B) preparing core-shell nanoparticles to which noble metal nanoparticles are attached by attaching noble metal nanoparticles to the surface of the first shell of the core-shell nanoparticles (hereinafter, core-shell nanoparticles to which noble metal nanoparticles are attached) manufacturing step);

(C) preparing a core-double shell nanoparticle by forming a second ceramic shell surrounding the core-shell nanoparticle to which the noble metal nanoparticle is attached (hereinafter, a core-double shell nanoparticle preparation step); and

(D) preparing magnetic-optical composite nanoparticles by attaching quantum dot nanoparticles to the surface of the second shell of the core-double shell nanoparticles (hereinafter, manufacturing magnetic-optical composite nanoparticles). there is.

In the present invention, (A) manufacturing core-shell nanoparticles is a step of preparing magnetic nanoparticles-ceramic core-shell nanoparticles by forming a first ceramic shell on magnetic nanoparticles.

The step may be performed by mixing the ceramic precursor solution with the first solution containing the magnetic nanoparticles, and through the above step, a second solution containing the first core-shell nanoparticles may be prepared.

In one embodiment, magnetic nanoparticles form the core of core-shell nanoparticles. The magnetic nanoparticles may be metal oxide nanoparticles, and the metal oxide may be FeO, Fe ₂ O ₃ , Fe ₃ O ₄ , CoFe ₂ O ₄ , NiFe ₂ O ₄ , MnFe ₂ O ₄ , TiO ₂ , ZrO ₂ , It may be one or more selected from the group consisting of CeO ₂ , Al ₂ O ₃ and MgO. In the present invention, magnetism can be imparted to the finally prepared magnetic-optical complex structure nanoparticles using the metal oxide.

The magnetic nanoparticles may be composed of clusters or self-assemblies of magnetic nanoparticles.

The average particle diameter of such magnetic nanoparticles, clusters, or self-assemblies is not limited as long as it is larger than noble metal nanoparticles and quantum dot nanoparticles described later, but may be, for example, 10 to 500 nm. In addition, the magnetic nanoparticles, clusters or self-assemblies may have a spherical shape. In the present invention, the term 'spherical' can encompass not only a sphere of mathematical definition, which is a three-dimensional shape consisting of all points at the same distance from one point, but also a shape that is round in appearance.

In one embodiment, the first ceramic shell may serve to protect the magnetic nanoparticles.

The ceramic may include at least one selected from the group consisting of silica, titania, zirconia, alumina, and zeolite, and in the present invention, a silica shell may be formed using silica.

The thickness of the first ceramic shell is not particularly limited, and for example, the thickness of the shell may be adjusted to 1 to 100 nm, 5 to 50 nm, or 1 to 20 nm.

In one embodiment, the first ceramic shell may be formed through a reaction between magnetic nanoparticles and a ceramic precursor. In this case, an alkoxy compound may be used as the ceramic precursor, and specifically, at least one selected from the group consisting of tetraethyl orthosilicate (TEOS) and tetramethyl orthosilicate (TMOS) may be used.

In the present invention, step (B) of producing core-shell nanoparticles attached with noble metal nanoparticles involves attaching noble metal nanoparticles to the core-shell nanoparticles prepared in step (A) to core-shell nanoparticles with attached noble metal nanoparticles. It is a step of manufacturing. In the present invention, core-shell nanoparticles to which noble metal nanoparticles are attached can be expressed as metal-enhanced fluorescence template nanoparticles.

In the present invention, the step (B) includes introducing a functional group to the surface of the first ceramic shell of the core-shell nanoparticle; and

A step of binding a noble metal nanoparticle to the functional group may be included.

In addition, in the present invention, step (B) introduces a functional group to the surface of the first ceramic shell of the core-shell nanoparticle;

bonding a noble metal nanoparticle seed to the functional group; and

A step of growing noble metal nanoparticle seeds bonded to the functional group to produce noble metal nanoparticles may be included.

Specifically, in step (B), a functional group-containing compound is added to the second solution prepared in step (A) to prepare a third solution including core-shell nanoparticles having a functional group introduced into the surface of the first ceramic shell. can do.

In addition, the 4-1 solution including core-shell nanoparticles to which noble metal nanoparticles are attached may be prepared by adding a noble metal nanoparticle solution to the third solution. Alternatively, a noble metal nanoparticle seed solution may be added to the third solution to prepare a solution including core-shell nanoparticles to which noble metal nanoparticle seeds are attached, and a noble metal ion precursor solution may be added to the solution to prepare a noble metal nanoparticle seed solution. The seed is grown into nanoparticles to prepare a 4-2 solution containing core-shell nanoparticles in which the grown noble metal nanoparticles are formed.

In one embodiment, the type of precious metal is not particularly limited, and may be, for example, gold, silver, platinum, copper, or an alloy thereof.

In the present invention, through the step of introducing a functional group to the surface of the first ceramic shell of the core-shell nanoparticle, the functional group is introduced to the surface of the first ceramic shell of the core-shell nanoparticle, and the functional group is a noble metal nanoparticle or a noble metal nanoparticle Can form multiple bonds with seeds.

In one embodiment, the functional group may be selected from the group consisting of an amine group (-NH), a thiol group (-SH), a carboxyl group (-COOH), a hydroxyl group (-OH), and dopamine. Specifically, the functional group may be an amine group, and the amine group may be introduced into the surface of the shell by reacting the core-shell nanoparticle with an amine group-containing compound.

In the step of binding the noble metal nanoparticle to the functional group of the present invention and the step of binding the noble metal nanoparticle seed to the functional group, the functional group forms a bond with the noble metal nanoparticle or the seed of the noble metal nanoparticle to form a bond on the core-shell nanoparticle. A noble metal nanoparticle or seed of a noble metal nanoparticle may be attached.

In this case, the noble metal nanoparticles or noble metal nanoparticle seeds may be prepared through a general manufacturing method in the art, and specifically, may be synthesized using a noble metal ion precursor solution and a reducing agent in an aqueous solution. Precious metal nanoparticles or noble metal nanoparticle seeds may be prepared by changing conditions such as the noble metal ion precursor, the type and concentration of the reducing agent, and the reaction temperature.

When gold is used as a noble metal, gold chloride trihydrate (HAuCl ₄ 3H ₂ O), potassium gold (III) chloride, K (AuCl ₄ ) and potassium dicyanoaurate (Potassium dicyanoaurate) are used as gold ion precursors. , KAu(CN) ₂ ) can be used, and when silver is used as a noble metal, silver nitrate (AgNO ₃ ) and potassium dicyanoaurate (KAg(CN) ₂ ) and at least one selected from the group consisting of silver acetate can be used. When platinum is used as a precious metal, potassium tetrachloroplatinate (K ₂ PtCl ₄ ), platinum chloride as a platinum ion precursor At least one selected from the group consisting of (platinum chloride PtCl ₄ ) and chloroplatinic acid (hexachloroplatinic acid, H ₂ PtCl ₆ ) may be used, and when copper is used as a noble metal, copper nitrate hydrate (Cu(NO ₃ ) ₂ 3H ₂ O) and copper sulfate pentahydrate (CuSO ₄ 5H ₂ O) may be used, and when palladium is used as a noble metal, palladium acetylacetonate as a palladium ion precursor ( At least one selected from the group consisting of palladium acetylacetonate, palladium chloride (PdCl ₂ ) and palladium nitrate hydrate (Pd(NO ₃ ) ₂ H ₂ O) may be used. In addition, a reducing agent consisting of sodium citrate (trisodium citrate, Na ₃ Cit), sodium borohydrate (NaBH ₄ ), hydroquinone, sodium ascorbate and hydroxyl amine One or more selected from the group may be used.

In addition, the synthesis may be carried out in the presence of a stabilizer, wherein at least one selected from the group consisting of PVP (polyvinylpyrrolidone), trisodium citrate and SDS (sodium dodecyl sulfate) may be used as the stabilizer. there is. In addition, the synthesis may be carried out by additionally using a magnetic nucleation inhibitor or the like, and potassium iodide may be used as a magnetic nucleation inhibitor of gold and acetonitrile may be used as a magnetic nucleation inhibitor of silver.

The reducing agent not only acts as a reducing agent for reducing noble metals in an aqueous solution, but also can impart negative charges around the synthesized noble metal nanoparticles. Therefore, the reduced noble metal nanoparticles or noble metal nanoparticle seeds are well dispersed in the aqueous solution due to the negative surface charge, and can strongly bind to functional groups such as amine groups. Therefore, the noble metal nanoparticle or the seed of the noble metal nanoparticle forms a strong bond with a functional group on the surface of the ceramic shell of the core-shell nanoparticle to attach or grow the noble metal nanoparticle to the core-shell nanoparticle, thereby forming the metal-enhanced fluorescence template nanoparticle. can be manufactured.

In one embodiment, after reacting the noble metal nanoparticle with the core-shell nanoparticle into which the functional group is introduced, a stabilizer may be further treated, and at this time, the above-described types may be used as the stabilizer without limitation.

In the present invention, when a noble metal nanoparticle seed is used, a step of growing the noble metal nanoparticle seed bonded to a functional group to produce a noble metal nanoparticle may be additionally performed.

The above step may be performed by adding a noble metal ion precursor solution to a solution containing core-shell nanoparticles to which noble metal nanoparticle seeds are attached. Through the above steps, it is possible to grow nanoparticles around the seeds using noble metal nanoparticle seeds as seeds, and the size and optical properties of the nanoparticles can be improved. At this time, as the noble metal ion precursor, the noble metal ion precursor used in the preparation of the seed may be used, and the above-mentioned kind may be used as the reducing agent. In addition, stabilizers of the kind described above may additionally be used.

The growth of the noble metal nanoparticle seed is achieved by attaching the noble metal nanoparticle seed to the ceramic surface of the core-shell nanoparticle and then growing so that the noble metal nanoparticle grows in contact with the ceramic surface, so it is firmly fixed, economical and process-efficient. has the advantage of being easy. In addition, when noble metal nanoparticles are grown, networking between the nanoparticles may occur to form a strong structure that can never be separated from the ceramic surface.

In one embodiment, the average particle diameter of the noble metal nanoparticles or grown noble metal nanoparticles may be 5 to 50 nm. Within the above range, a wavelength range in which metal-enhanced fluorescence is possible can be adjusted.

In the present invention, the step (C) of preparing the core-double shell nanoparticle is a step of preparing the core-double shell nanoparticle by forming a second ceramic shell surrounding the core-shell nanoparticle to which the noble metal nanoparticle is attached.

The step may be performed by mixing the ceramic shell precursor solution with the 4-1 solution or the 4-2 solution prepared in step (B), and the core-double shell nanoparticles on which the second ceramic shell is formed through the above step. A fifth solution containing a can be prepared.

In one embodiment, the second ceramic shell protects the core-shell nanoparticles to which the noble metal nanoparticles are attached, that is, the metal-enhanced fluorescence template nanoparticles, and at the same time increases the distance between the noble metal nanoparticles and quantum dot nanoparticles to be attached later. can play a regulatory role.

As the ceramic, the above-described types may be used without limitation in the first ceramic shell, and for example, at least one selected from the group consisting of silica, titania, alumina, zirconia, and zeolite may be used. In the present invention, the second ceramic shell may be formed using silica.

In one embodiment, the second ceramic shell may be formed through a reaction between core-shell nanoparticles to which noble metal nanoparticles are attached and a ceramic precursor. In this case, an alkoxy compound may be used as the ceramic precursor, and specifically, at least one selected from the group consisting of tetraethyl orthosilicate (TEOS) and tetramethyl orthosilicate (TMOS) may be used. In the present invention, the thickness of the secondary ceramic shell can be adjusted by varying the content of the precursor.

In one embodiment, the thickness of the second ceramic shell is 5 nm to 100 nm, 5 to 50 nm, or 5 to 20 nm, and noble metal nanoparticles may be included in the second ceramic shell.

In the present invention, (D) manufacturing magnetic-optical composite nanoparticles is a step of preparing magnetic-optical composite nanoparticles by attaching quantum dot nanoparticles to the surface of the second shell of the core-double shell nanoparticles.

Specifically, the above step may be performed by adding a functional group-containing compound to the fifth solution prepared in step (C), and the sixth solution containing nanoparticles having a functional group introduced into the surface of the second ceramic shell through the above step. solution can be prepared. In addition, a seventh solution including magnetic-optical composite structure nanoparticles may be prepared by adding quantum dot nanoparticles to the sixth solution.

In the present invention, step (D) introduces a functional group to the surface of the second ceramic shell; and binding quantum dot nanoparticles to the functional group.

In one embodiment, the functional group may be selected from the group consisting of a thiol group (-SH), an amine group (-NH2), a carboxyl group (-COOH), and a hydroxyl group (-OH). Specifically, the functional group may be a thiol group, and a thiol group may be introduced to the surface of the shell by reacting the core-double shell nanoparticle with a compound containing a thiol group.

In one embodiment, the functional group is strongly bonded to the quantum dot nanoparticle, so that the quantum dot nanoparticle can be attached to the core-double shell nanoparticle.

In one embodiment, the quantum dot nanoparticles are cadmium selenide (CdSe), cadmium sulfide (CdS), zinc oxide (ZnO), zinc selenide (ZnSe), zinc sulfide (ZnS) manganese-doped zinc sulfide (Mn-doped ZnS), indium phosphide (InP), and cesium lead halide (CsPbBr ₃ , CsPbI ₃ ) may include at least one selected from the group consisting of quantum dots.

These quantum dot nanoparticles can be prepared through a general manufacturing method in the art, and specifically, can be synthesized using a quantum dot ion precursor, a reducing agent, and a stabilizer in an organic solvent. In this case, the quantum dot ion may be zinc, sulfur, manganese, cadmium, selenium, indium, phosphorus, cesium, lead, bromine, or iodine.

At least one selected from the group consisting of zinc chloride dehydrate (ZnCl2), zinc acetate and zinc nitrate may be used as the zinc ion precursor, and sulfur powder as the sulfur ion precursor And at least one selected from the group consisting of dodecyl mercaptan (1-dodecanethiol) may be used, and at least one selected from the group consisting of manganese chloride and manganese nitrate may be used as a manganese ion precursor, , At least one selected from the group consisting of cadmium oxide and cadmium chloride may be used as a cadmium ion precursor, and a group consisting of selenium powder and selenium oxide as a selenium ion precursor. At least one selected from may be used, and at least one selected from the group consisting of indium acetate, indium chloride, and indium fluoride may be used as the indium ion precursor, and as the phosphorus ion precursor Tris (trimethylsilyl) phosphine may be used, and at least one selected from the group consisting of cesium bromide and cesium iodide may be used as a cesium ion precursor, and lead bromide (lead ion precursor) may be used. At least one selected from the group consisting of lead bromide and lead iodide may be used. In addition, at least one selected from the group consisting of dibenzylamine, oleylamine, oleic acid, and octadecylamine may be used as a reducing agent and a stabilizer, and octadecene (octadecene) may be used as a solvent. ), dimethylformamide (DMF), and at least one selected from the group consisting of toluene may be used.

In one embodiment, the size of the quantum dot nanoparticles may be 3 to 15 nm.

In addition, the present invention relates to magnetic-optical complex structure nanoparticles. Magnetic-optical composite structure nanoparticles according to the present invention can be prepared by the above-described manufacturing method.

The magnetic-optical complex structure nanoparticle according to the present invention includes a core-shell nanoparticle including a magnetic nanoparticle core and a first ceramic shell;

noble metal nanoparticles formed on the surface of the first ceramic shell of the core-shell nanoparticles;

a second ceramic shell surrounding the core-shell nanoparticles on which the noble metal nanoparticles are formed; and

Quantum dot nanoparticles formed on a surface of the second ceramic shell may be included.

The magnetic-optical composite structure nanoparticles according to the present invention include magnetic nanoparticles, noble metal nanoparticles, and quantum dot nanoparticles, so that magnetic and optical functions can be realized at the same time.

In one embodiment, the noble metal nanoparticle bound to the surface of the core-shell nanoparticle may be included in the second ceramic shell. Therefore, the quantum dot nanoparticles may be located outside the noble metal nanoparticles bonded to the surface of the core-shell nanoparticles.

In particular, in the present invention, optical performance can be improved by using a metal-enhanced fluorescence (MEF) phenomenon between noble metal nanoparticles and quantum dot nanoparticles. Metal-enhanced fluorescence (MEF) is a phenomenon in which when a specific metal and a phosphor are connected by covalent or non-covalent bonds at a certain distance, the luminous efficiency increases and the phosphor emits light brighter than the maximum value of its original brightness. it means. In the present invention, the emission efficiency of quantum dot nanoparticles can be improved through metal-enhanced fluorescence (MEF) between noble metal nanoparticles and quantum dot nanoparticles having fluorescent properties, and target cells can be imaged using the improved emission signal. In particular, in the present invention, the emission characteristics of the quantum dot nanoparticles can be adjusted according to the purpose of use by adjusting the distance between the noble metal nanoparticle and the quantum dot nanoparticle through the second ceramic shell.

In addition, the present invention relates to a composition for diagnostic imaging, a kit for detecting an analyte, or a molecular diagnostic chip including the above-described magnetic-optical composite structure nanoparticles.

In addition, the present invention includes the steps of functionalizing a biomolecule capable of binding to an analyte to be detected on the surface of the magnetic-optical composite structure nanoparticle;

exposing the functionalized magnetic-optical composite nanoparticles to a sample containing one or more analytes; and

It relates to a method for imaging or detecting an analyte, comprising identifying an analyte bound to a magnetic-optical composite structure nanoparticle using photoluminescence spectroscopy.

The magnetic-optical complex nanoparticles according to the present invention are functionalized with biomolecules capable of recognizing analytes to be detected, and can be used as probes that can be applied to detect various target biomolecules.

In one embodiment, the analyte to be detected is an amino acid, peptide, polypeptide, protein, glycoprotein, lipoprotein, nucleoside, nucleotide, oligonucleotide, nucleic acid, sugar, carbohydrate, oligosaccharide, polysaccharide, fatty acid , lipids, hormones, metabolites, cytokines, chemokines, receptors, neurotransmitters, antigens, allergens, antibodies, substrates, metabolites, cofactors, inhibitors, drugs, pharmaceuticals, nutrients, prions, toxins, poisons, explosives, It may be pesticides, chemical weapons, biohazardous agents, radioisotopes, vitamins, heterocyclic aromatic compounds, carcinogens, mutagens, anesthetics, amphetamines, barbiturates, hallucinogens, wastes or pollutants. In addition, when the analyte is a nucleic acid, the nucleic acid may include genes, viral RNA and DNA, bacterial DNA, fungal DNA, mammalian DNA, cDNA, mRNA, RNA and DNA fragments, oligonucleotides, synthetic oligonucleotides, modified oligonucleotides, single It can be stranded and double-stranded nucleic acids, natural and synthetic nucleic acids.

In one embodiment, the biomolecule capable of recognizing the analyte and capable of binding to the surface of the multi-structured nanoparticle according to the present invention is an antibody, antibody fragment, genetically engineered antibody, single chain antibody, receptor protein, binding protein, enzymes, inhibitor proteins, lectins, cell adhesion proteins, oligonucleotides, polynucleotides, nucleic acids or aptamers.

In the photoluminescence spectroscopy method using the magnetic-optical complex structured nanoparticles according to the present invention, metal-enhanced fluorescence appears due to the interaction between the noble metal part of the nanoparticles and the quantum dots, which can indicate stronger signal strength, and can be detected even when the amount of analyte is small. this could be possible In addition, magnetic separation of the analyte bound to the magnetic-optical composite structure nanoparticles is possible using magnetic properties, and it can be used for ultra-sensitive biomolecular analysis, and is also very useful as in vitro diagnosis and imaging technology.

Hereinafter, the present invention will be described in more detail through examples. These examples are only intended to easily explain the present invention, and it is obvious that the scope of the present invention is not limited to the presented examples.

Example

Example 1. Preparation of magnetic-optical composite structure nanoparticles

1) Magnetite (Fe ₃ O ₄ ) Synthesis of nanoparticles

Synthesis of iron oxide, specifically, magnetite (Fe ₃ O ₄ ) nanoparticles was performed through a polyol method.

Iron chloride hexahydrate (FeCl ₃ 6H ₂ O) is an iron ion precursor, ethylene glycol (EG) is a reducing agent and solvent, sodium acetate (NaOAc), H ₂ O is a hydrolysis was used as an adjuvant.

2 mmol of FeCl3·6H ₂ O 2 mmol, 6 mmol of NaOAc, and 150 mmol of H ₂ O were added to 50 mL of EG, and the mixture was placed in a three-necked flask and rapidly heated to 200° C. for 15 minutes with mechanical stirring. The reaction time was maintained at 3 hours and 30 minutes, cooled, washed with ethanol, and dispersed in ethanol (preparation of the first solution).

2) Synthesis of gold nanoparticles or gold nanoparticle seeds

In the synthesis of gold nanoparticles, gold chloride trihydrate (HAuCl ₄ 3H ₂ O) was used as a gold ion precursor, trisodium citrate (Na ₃ Cit) as a reducing agent and stabilizer, and H ₂ O as a solvent. .

After heating 100 mL of HAuCl ₄ ·3H ₂ O 1 mM to 100°C, 10 mL of Na ₃ Cit 38.8 mM was injected while maintaining magnetic stirring. The reaction proceeded for 1 hour, cooled to room temperature, and stored at room temperature.

Also, in the synthesis of gold nanoparticle seeds, HAuCl ₄ 3H ₂ O was used as a gold ion precursor, sodium borohydrate (NaBH ₄ ) as a reducing agent, Na ₃ Cit as a stabilizer, and H ₂ O as a solvent.

To 50 mL of H ₂ O, the concentration of HAuCl ₄ 3H ₂ O was adjusted to 0.25 mM and the concentration of Na ₃ Cit to 0.25 mM, and 1.5 mL of 0.1M NaBH ₄ was added. It was reacted at room temperature for 6 hours while maintaining magnetic stirring.

3) Preparation of core-shell nanoparticles with gold nanoparticles attached

First, a silica shell was formed on the iron oxide nanoparticles using the Stober method.

Ethanol and water (H ₂ O) are solvents, ammonium hydroxide solution (NH ₄ OH) is a catalyst, tetraethyl orthosilicate (TEOS) is a silica precursor, and polyvinylpyrrolidone (PVP) ) was used as a stabilizer.

60 mL of ethanol, 9 mL of H ₂ O, and 3 mL of NH ₄ OH were mixed. 30 mg of iron oxide nanoparticles (first solution) was put into the solution. After adding 0.060 mL of TEOS to a uniform mixture of iron oxide nanoparticles, the mixture was shaken at room temperature for 2 hours. Then, it was washed with ethanol and dispersed in 12 mL of ethanol. Through this, iron oxide nanoparticles-silica core-shell nanoparticles were synthesized (second solution preparation).

Gold nanoparticles or gold nanoparticle seeds were attached to the iron oxide nanoparticle-silica core-shell nanoparticles.

First, iron oxide nanoparticles-silica core-shell nanoparticles were functionalized.

(3-Aminopropyl)triethoxysilane (APTES) was used as a precursor of the amine group (-NH ₂ ), and 2-propanol was used as a solvent.

4 mL of ethanol containing the second solution, iron oxide nanoparticles-silica core-shell nanoparticles, was solvent-substituted with 10 mL of 2-propanol, and 0.10 mL of APTES was added and shaken. After sonication at 80° C. for 4 hours, the mixture was washed with H ₂ O and dispersed in 5 mL of H ₂ O (third solution prepared).

5 mL of the third solution containing iron oxide nanoparticles-silica core-shell nanoparticles functionalized with amine groups on the surface and 25 mL of gold nanoparticle solution or gold nanoparticle seed solution were mixed and shaken for 16 hours. And as a post-treatment, 20 mL of H ₂ O in which 1 wt% of PVP was dissolved was added as a stabilizer and shaken uniformly. Then, it was washed with H ₂ O and dispersed in 20 mL of H ₂ O (preparation of solution 4-1/using gold nanoparticle solution).

When the gold nanoparticle seed solution was used, the gold nanoparticle seeds attached to the surface were grown into gold nanoparticles.

PVP was used as a stabilizer, ascorbic acid (L-ascorbic acid) as a reducing agent, and tetrachloric acid hydrate (HAuCl ₄ 3H ₂ O) as a gold ion precursor.

After putting 10 mg of iron oxide-silica core-shell nanoparticles with gold nanoparticle seeds attached to 200 mL of H ₂ O containing 1 wt% of PVP, 4 mL of 20 mM ascorbic acid aqueous solution was added and shaken to mix uniformly. Then, 6 mL of 5 mM HAuCl ₄ 3H ₂ O aqueous solution was divided into 6 times at intervals of 10 minutes. It reacted for 1 hour while shaking at room temperature. It was washed with H ₂ O and ethanol and dispersed in 20 mL of ethanol (preparation of solution 4-2).

4) Formation of a second silica shell on the surface of core-shell nanoparticles (metal-enhanced fluorescence template nanoparticles) to which gold nanoparticles are attached (preparation of core-double shell nanoparticles)

A silica shell was formed in a solution (solution 4-1 or solution 4-2) containing metal-enhanced fluorescence template nanoparticles, which are iron oxide-silica core-shell nanoparticles bonded to gold nanoparticles, using a stover method.

Ethanol and water (H ₂ O) were used as solvents, aqueous ammonia (NH ₄ OH) as a catalyst, and tetraethyl orthosilicate (TEOS) as a silica precursor.

1 mL of ethanol, 0.15 mL of H ₂ O, and 0.1 mL of NH ₄ OH were mixed. 0.5 mg of metal-enhanced fluorescence template nanoparticles was added into the solution. 0.001 to 0.006 mL of TEOS was added at a rate of 0.001 mL per 10 minutes to obtain the desired silica thickness (3 nm, 5 nm, 10 nm, 20 nm, 30 nm, and 35 nm) in a uniform mixture of metal-enhanced fluorescence template nanoparticles. After adding, it was shaken at room temperature. And washed with ethanol and dispersed in 10 mL of ethanol (preparation of the fifth solution).

In the present invention, Figure 2 is a schematic diagram showing the thickness change of the second silica shell according to the amount of orthosilicate (TEOS) and a transmission electron micrograph (a) and a graph showing the results of measuring the thickness of the second silica shell (b) to be. In FIG. 2, metal-enhanced fluorescence template nanoparticles were prepared using the 4-2 solution.

5) Second silica shell surface functionalization of core-double shell nanoparticles

In order to attach quantum dots, the surface of the second silica shell of the core-double shell nanoparticles was functionalized.

(3-Mercaptopropyl)trimethoxysilane (MPTS) was used as a precursor of a thiol group (-SH) and ethanol was used as a solvent.

0.50 mL of MPTS was added to 10 mL of ethanol containing core-double shell nanoparticles as the fifth solution and shaken. The reaction proceeded at 25 °C for 16 hours. Washed with ethanol, and dispersed in 1 mL of ethanol (preparation of the sixth solution).

6) Synthesis of zinc sulfide (ZnS) quantum dot nanoparticles and cadmium selenide (CdSe) nanoparticles doped with manganese (Mn)

In the synthesis of manganese-doped zinc sulfide quantum dot nanoparticles, zinc chloride (ZnCl ₂ ) is used as a zinc ion precursor, sulfur powder is used as a sulfur ion precursor, and manganese chloride (MnCl ₂ ) is used as a manganese ion precursor. As an ionic precursor, dibenzylamine was used as a solvent and reducing agent.

0.4 g of ZnCl ₂ , 20 mg of MnCl ₂ , and 0.6 g of sulfur powder were added to 54 mL of dibenzylamine, followed by magnetic stirring. It was rapidly heated from 25 °C to 120 °C for 10 minutes, and the reaction time was maintained for 1 hour. Then, it was rapidly heated to 260° C. for 15 minutes, and the reaction time was maintained. The temperature was lowered to 150° C. in a room temperature atmosphere, and a mixed solution of 0.4 g of ZnCl ₂ and 5 mL of dibenzylamine was added. Then, it was rapidly heated to 260° C. for 15 minutes, and the reaction was maintained for 15 minutes. After cooling the reaction solution at room temperature, it was stabilized by adding 5 mL of oleylamine. After that, it was washed with ethanol and dispersed in chloroform.

In the synthesis of cadmium selenide quantum dot nanoparticles, cadmium oxide (CdO) is used as a cadmium ion precursor, octadecene (ODE) as a non-coordinating solvent, oleic acid (OA) as a surfactant, and octadecylamine ( octadecylamine (ODA) was used as a stabilizer, selenium (Se) as a selenium ion precursor, and trioctylphosphine (TOP) as a selenium coordination solvent.

After dissolving 0.26 g of CdO in 40 mL of ODE in a three-necked flask, 2 mL of OA was injected. Under a nitrogen atmosphere, the mixed solution was rapidly heated to 160° C. within 10 minutes and held for 1 hour. Then, it was rapidly heated to 260° C. within 10 minutes, and the solution became clear during this process. After maintaining 260°C for 30 minutes, it was naturally cooled to 200°C. 3 g of ODA was injected into the mixed solution and quickly heated to 300 ° C within 10 minutes. When the solution reached 300° C., 0.78 g of Se was dissolved in 5 mL of TOP, injected into the mixed solution, and then reacted for 5 minutes to prepare cadmium selenide quantum dots. After rapidly cooling to room temperature, washed with chloroform (CHCl ₃ ) and ethanol and dispersed in chloroform.

7) Manufacture of magnetic-optical composite structure nanoparticles

In this step, when using zinc sulfide quantum dots doped with manganese, solution 4-2 was used, and when using cadmium selenide quantum dots, solution 4-1 was used.

1 mL of ethanol containing thiol group-functionalized core-double shell nanoparticles, which is the sixth solution, was shaken with 0.2 mL (10 mg/mL) of chloroform containing manganese-doped zinc sulfide quantum dots or cadmium selenide quantum dots. . The reaction proceeded at 25 °C for 16 hours. Thereafter, magnetic separation was performed to remove unattached quantum dots to prepare magnetic-optical complex structure nanoparticles and dispersed in 2 mL of ethanol (a seventh solution was prepared).

Comparative Example 1.

Steps 3) to 5) of Example 1 were not performed, and steps 6) to 7) were performed in the same manner to prepare magnetic-optical nanoparticles not containing noble metal (gold) nanoparticles.

Experimental Example 1. Physical properties of magnetic-optical composite structure nanoparticles

In Figure 1 (a) shows a schematic diagram of the manufacturing process (steps) of the magnetic-optical composite structure nanoparticles according to the present invention and transmission electron microscope (TEM) pictures at each step.

In addition, (b) uses the phenomenon that metal-enhanced fluorescence (MEF) appears when a fluorescence signal is generated around plasmonic nanoparticles such as gold nanoparticles, and applies it to magnetic-optical composite structure nanoparticles to produce quantum dot nanoparticles. It is a schematic diagram showing that the fluorescence signal is increased. In the present invention, the fluorescence signal can be maximized by adjusting the distance between the noble metal nanoparticle and the quantum dot nanoparticle using the thickness of the second silica shell.

In FIG. 3 (a) shows a transmission electron microscope image of manganese-doped zinc sulfide quantum dot nanoparticles and cadmium selenide nanoparticles, and also shows a transmission electron microscope image of the magnetic-optical composite structure nanoparticles prepared in Example The results measured by a photoluminescence spectrometer (Photoluminescence, PL) are shown. The left graph was measured with a wavelength of 310 nm, and the right graph was measured with a wavelength of 532 nm.

In FIG. 3 (b) is a transmission electron microscope image and an energy dispersive spectroscopy (EDS) image of magnetic-optical composite structure nanoparticles prepared using zinc sulfide quantum dot nanoparticles doped with manganese. Through the energy dispersive spectroscopy image, it can be confirmed that magnetic nanoparticles, gold nanoparticles, and quantum dot nanoparticles are present in the magnetic-optical composite structure nanoparticles.

3 (a) and (b), the thickness of the second silica shell is 10 nm.

In addition, (a) in FIG. 4 shows magnetic-optical nanoparticles (Bare without Au) prepared in Comparative Example 1 and four types of magnetic-optical composites prepared in Example according to the distance between noble metal nanoparticles and quantum dot nanoparticles. A schematic diagram of structural nanoparticles (using cadmium selenide quantum dot nanoparticles) and transmission electron micrographs are shown.

(b) shows the hydrodynamic size of the four types of magnetic-optical composite structure nanoparticles (using cadmium selenide quantum dot nanoparticles) prepared in Example by using Dynamic Light Scattering (DLS). As shown in (b) of FIG. 4, it can be seen that the hydrodynamic size increases with the same tendency as the thickness of the silica shell increases.

In addition, (c) shows the fluorescence signal intensity after drying the four types of magnetic-optical composite structure nanoparticles (using cadmium selenide quantum dot nanoparticles) prepared in Comparative Examples and Examples on a cover glass. The results measured by a confocal Raman-fluorescence microscope (Confocal Raman Microscopy) are shown. At this time, a 40x objective lens was used and a laser wavelength of 532 nm was used. The power during laser irradiation was measured as 0.139 mW, and the acquisition time was measured as 1 second.

Based on the comparative example without noble metal nanoparticles, when the silica shell is as thin as 5 nm, fluorescence quenching by noble metal nanoparticles occurs, and when it becomes 10 nm, fluorescence intensity is increased by metal-enhanced fluorescence. there is. In addition, at 15 nm and 20 nm, it can be seen that the interaction between the noble metal nanoparticle and the fluorescent quantum dot is reduced, showing almost similar results to those of the comparative example.

Experimental Example 2. Target cell imaging using magnetic-optical complex structure nanoparticles

Surface functionalization was performed for biomolecular detection of the magnetic-optical composite structure nanoparticles prepared in Examples. The magnetic-optical complex structure nanoparticles used above were prepared using cadmium selenide quantum dot nanoparticles.

First, a silica shell was formed on the magnetic-optical composite structure nanoparticles prepared in Examples using the Stover method.

Ethanol and water (H ₂ O) were used as solvents, aqueous ammonia (NH ₄ OH) as a catalyst, and tetraethyl orthosilicate (TEOS) as a silica precursor.

0.15 mL of H ₂ O and 0.05 mL of NH ₄ OH were added to 2 mL of ethanol, mixed uniformly, and 0.001 mL of TEOS was added and shaken for 2 hours to coat the silica shell. Washed with ethanol and dispersed in 20 mL of ethanol.

Then, in order to attach biomolecules, the silica-coated magnetic-optical complex structure nanoparticles were functionalized.

Succinimidyl ester-polyethylene glycol with a molecular weight of 5,000 daltons, using (3-aminopropyl)triethoxysilane (APTES) as a precursor of an amine group (-NH ₂ ) and sodium dodecyl sulfate (SDS) as a stabilizer. -Carboxymethyl (Succinimidyl ester-polyethyleneglycol-carboxymethyl, SC-PEG-COOH) as a stabilizer for magnetic-optical composite structure nanoparticles and a precursor of carboxyl group (-COOH), 1-ethyl-3-(3-dimethylaminopropyl) ) Carbodiimide (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and sulfo-N-hydroxysuccinimide (sulfo-NHS) as catalysts for amide bonding, ethanol and Phosphate buffered saline (PBS) was used as a solvent and cyclic arginine-glycine-aspartic acid tripeptide (cRGD) was used to capture integrin, a receptor expressed on the cell surface.

0.05 mL of APTES was injected into 1 mL of the prepared nanoparticles (silica-coated magnetic-optical composite structure nanoparticles) and shaken for 16 hours. It was washed with H ₂ O and dispersed in 1 mL of 0.01% SDS solution (including 0.05 mg/mL of iron oxide nanoparticles). 0.05 mL of 1 mM SC-PEG-CM was mixed with the nanoparticle solution, and after blocking the light with aluminum foil, the mixture was shaken for 16 hours. After this, it was washed with H ₂ O and dispersed in 1 mL of H ₂ O. In this process, carboxyl groups were modified on the surface of the silica-coated magnetic-optical composite structure nanoparticles. 20 mM EDC and 0.05 mL of sulfo-NHS were added to the solution and shaken for 30 minutes. It was washed with PBS and dispersed in 1 mL. Then, 0.1 mL of 1 mM cRGD was mixed with the above solution and shaken for 3 hours after blocking light with aluminum foil. After washing with H ₂ O or PBS, it was dispersed in 0.5 mL.

0.025 mL of the magnetic-optical composite structure nanoparticle solution functionalized with the cRGD was incubated for at least 3 hours in a glass bottom dish to which 70,000 U87MG cells and MCF7 cells were attached, respectively, and then fixed. did In addition, cell imaging was performed using a confocal Raman-fluorescence microscope. At this time, a 40x objective lens was used, the laser wavelength was 532 nm, the laser power was 0.139 mW, and the acquisition time was measured at 0.035 seconds per 1 μm * 1 μm pixel.

In FIG. 5, (a) is a schematic diagram of detecting integrin receptors present in the cell membrane of cancer cells with magnetic-optical composite structure nanoparticles functionalized with cRGD and performing cell imaging with fluorescence characteristics of quantum dot nanoparticles.

In U87MG cells with a high level of integrin expression on the cell surface, many magnetic-optical complex structured nanoparticles functionalized with cRGD are attached to the cells, resulting in fluorescence on the cell surface, but MCF7 cells with a low level of integrin expression on the cell surface. In , the magnetic-optical complex structure nanoparticles functionalized with cRGD are not attached, so fluorescence does not appear on the cell surface. Therefore, target-specific cancer cell imaging is possible using the magnetic-optical composite structure nanoparticles according to the present invention.

Experimental Example 3. Detection of biomaterials using magnetic-optical composite structure nanoparticles

The surface functionalization of the carboxyl group of the magnetic-optical composite structure nanoparticles prepared in Example was performed using thiol-polyethylene-carboxymethyl (SH-PEG-COOH) with a molecular weight of 5,000 Daltons, H ₂ O and acetone. It was carried out using a solvent. The magnetic-optical complex structure nanoparticles used above were prepared using zinc sulfide quantum dot nanoparticles doped with manganese.

1 mg of the magnetic-optical composite nanoparticles prepared in Example was uniformly mixed with 5 mL of acetone and 1 mL of chloroform containing 1 mM SH-PEG-COOH, and shaken for 16 hours. Washed with H ₂ O and dispersed in 5 mL of H ₂ O. Then, an antibody used to detect the virus, influenza A antibody, was functionalized. 3 mL of H ₂ O containing the magnetic-optical composite structure nanoparticles was added to 1 mL (50 mM) of 2-(N-morpholino)ethanesulfonic acid (MES) buffer. After solvent replacement, 0.150 mL of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) (20 mM) solution, 0.150 mL of sulfo-N-hydroxysuccinimide (NHS) (20 mM) solution were mixed and shaken for 30 minutes. And washed with PBS, and dispersed in 1 mL of PBS. Thereafter, 0.1 mL of an influenza A antibody (0.100 g) solution was added and stirring was performed for at least 16 hours. And washed with PBS, and dispersed in 0.6 mL of the solution.

The magnetic-optical composite nanoparticles functionalized with the influenza A antibody were reacted with the influenza A virus. Then, it was put into an immunochromatography rapid test (Lateral Flow Assay, LFA) device and detected by colorimetric analysis.

In FIG. 6 (a), magnetic-optical composite structure nanoparticles modified with a specific antibody bind to antigens in a sample, and a concentrated sample obtained by sorting them by magnetic separation is a schematic diagram of a process of detecting fluorescence in an LFA device. .

In FIG. 6, (b) shows the result of measurement with an LFA device while adjusting the concentration of influenza A antigen using the magnetic-optical composite structure nanoparticles modified with influenza A antibody.

Through the figure, it can be confirmed that the fluorescence intensity appears differently depending on the infection concentration.

Claims (20)

preparing a core-shell nanoparticle by forming a first ceramic shell on the magnetic nanoparticle;
attaching noble metal nanoparticles to the surface of the first ceramic shell of the core-shell nanoparticles to produce core-shell nanoparticles to which noble metal nanoparticles are attached;
preparing a core-double shell nanoparticle by forming a second ceramic shell surrounding the core-shell nanoparticle to which the noble metal nanoparticle is attached; and
Attaching quantum dot nanoparticles to the surface of the second ceramic shell of the core-double shell nanoparticles to prepare magnetic-optical composite structure nanoparticles,
The second ceramic shell has a thickness of 5 nm to 50 nm, and a method for producing magnetic-optical composite nanoparticles exhibiting metal-enhanced fluorescence (MEF).
According to claim 1,
Magnetic nanoparticles are from the group consisting of FeO, Fe ₂ O ₃ , Fe ₃ O ₄ , CoFe ₂ O ₄ , NiFe ₂ O ₄ , MnFe ₂ O ₄ , TiO ₂ , ZrO ₂ , CeO ₂ , Al ₂ O ₃ and MgO. A method for producing magnetic-optical composite structure nanoparticles comprising one or more selected metal oxide nanoparticles.
According to claim 1,
A method for producing magnetic-optical composite nanoparticles having an average particle diameter of 10 to 500 nm.
According to claim 1,
In the first ceramic shell and the second ceramic shell, the first ceramic and the second ceramic each contain at least one selected from the group consisting of silica, titania, zirconia, alumina, and zeolite. Method for producing magnetic-optical composite structure nanoparticles .
According to claim 1,
The first ceramic shell has a thickness of 1 to 100 nm. Method for producing magnetic-optical composite structure nanoparticles.
According to claim 1,
The step of preparing core-shell nanoparticles to which noble metal nanoparticles are attached is
introducing a functional group to the shell surface of the core-shell nanoparticle; and
A method for producing a magnetic-optical composite structure nanoparticle comprising the step of binding a noble metal nanoparticle to the functional group.
According to claim 1,
The step of preparing core-shell nanoparticles to which noble metal nanoparticles are attached is
introducing a functional group to the shell surface of the core-shell nanoparticle;
bonding a noble metal nanoparticle seed to the functional group; and
A method for producing a magnetic-optical composite structure nanoparticle comprising the step of growing a noble metal nanoparticle seed bonded to the functional group to produce a noble metal nanoparticle.
According to claim 1,
A method for producing magnetic-optical complex structured nanoparticles in which the noble metal is gold, silver, platinum, copper, or an alloy thereof.
According to claim 6 or 7,
The functional group is a magnetic-optical composite structure nanoparticle comprising at least one selected from the group consisting of an amine group (-NH), a thiol group (-SH), a carboxyl group (-COOH), a hydroxyl group (-OH), and dopamine. manufacturing method.
According to claim 6 or 7,
A method for producing magnetic-optical composite nanoparticles having an average particle diameter of 5 to 50 nm of noble metal nanoparticles bonded to functional groups or grown noble metal nanoparticles.
According to claim 1,
A method for producing a magnetic-optical composite structure nanoparticle, wherein the noble metal nanoparticle is contained in the second ceramic shell.
According to claim 1
The step of attaching the quantum dot nanoparticles to the second shell ceramic surface of the core-double shell nanoparticles is
introducing a functional group to the surface of the second ceramic shell; and
A method for producing a magnetic-optical composite structure nanoparticle comprising the step of binding the quantum dot nanoparticle to the functional group.
According to claim 12,
The functional group is a magnetic-optical composite structure nanoparticle comprising at least one selected from the group consisting of an amine group (-NH), a thiol group (-SH), a carboxyl group (-COOH), a hydroxyl group (-OH), and dopamine. manufacturing method.
According to claim 1,
Quantum dot nanoparticles are cadmium selenide (CdSe), cadmium sulfide (CdS), zinc oxide (ZnO), zinc selenide (ZnSe), zinc sulfide (ZnS), manganese-doped zinc sulfide (Mn-doped ZnS), Indium (InP) and cesium lead halide (CsPbBr ₃ , CsPbI ₃ ) Method for producing a magnetic-optical composite structure nanoparticles comprising at least one selected from the group consisting of quantum dots.
Core-shell nanoparticles including a magnetic nanoparticle core and a first ceramic shell;
noble metal nanoparticles formed on the surface of the first ceramic shell of the core-shell nanoparticles;
a second ceramic shell surrounding the core-shell nanoparticles on which the noble metal nanoparticles are formed; and
Magnetic-optical composite structure nanoparticles comprising quantum dot nanoparticles formed on the surface of the second ceramic shell.
According to claim 15,
The quantum dot nanoparticles are located outside the noble metal nanoparticles bonded to the surface of the core-shell nanoparticles. Magnetic-optical composite structure nanoparticles.
A composition for diagnostic imaging comprising the magnetic-optical composite structure nanoparticles according to claim 15.
Functionalizing a biomolecule capable of binding to an analyte to be detected on the surface of the magnetic-optical composite structure nanoparticle according to claim 15;
exposing the functionalized magnetic-optical composite nanoparticles to a sample containing one or more analytes; and
A method of imaging or detecting an analyte comprising identifying an analyte bound to a magnetic-optical composite structure nanoparticle using photoluminescence spectroscopy.
A kit for detecting an analyte comprising the magnetic-optical composite nanoparticles according to claim 15.
A molecular diagnostic chip comprising the magnetic-optical complex structure nanoparticles according to claim 15 .

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