KR101812674B1 - Particle including quantum dot for multiplexing analysis and method for manufacturing the same - Google Patents

Abstract

 The disclosed multiple detection particle includes an encoding region and a probe region coupled with the encoding region, wherein the encoding region comprises a polymeric resin forming a porous support and a quantum dot chemically bonded to the polymeric resin. Therefore, the binding stability of the quantum dot can be improved in the multiple detection particles.

Description

TECHNICAL FIELD [0001] The present invention relates to a multi-detection particle including a quantum dot and a method for manufacturing the same.

TECHNICAL FIELD The present invention relates to a multi-detecting particle, and more particularly, to a multi-detecting particle including a quantum dot and a manufacturing method thereof.

Quantum dots are nanoparticles having a size of several tens of nanometers or less, which have semiconductor characteristics, and have properties different from those of bulk particles due to the quantum confinement effect. Specifically, the bandgap varies according to the size of the quantum dot, and the wavelength to be absorbed can be changed. The quantum confinement effect due to the small size exhibits new optical, electrical, and physical characteristics not seen in bulk materials.

Recently, quantum dots have been applied in the field of biotechnology. It is known that it can be used as a means of encoding detection particles for detecting targets such as proteins, nucleic acid sequences or viruses, for example. In order for the quantum dot to function as an encoding means, it needs to be fixed to a support or a binder in the encoding region.

As a means for fixing the quantum dots in the encoding region, a method of physically trapping or sealing the quantum dots is known.

However, according to the method of physically fixing the quantum dot particles as described above, it is necessary to perform a separate step for fixing the quantum dot particles, or the density difference between the encoding region and the probe region becomes large, (Patterning) is difficult, or deformation occurs later.

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and it is an object of the present invention to provide a multiple detection particle including a porous support having improved binding stability to a quantum dot and a method for producing the same.

According to an embodiment of the present invention for realizing the object of the present invention, the multiple detection particle includes an encoding region and a probe region coupled with the encoding region, wherein the encoding region comprises a polymer resin forming a porous support, And a quantum dot chemically bonded to the polymer resin.

In one embodiment, the polymer resin includes a polyethylene glycol-based resin.

In one embodiment, the encoding region includes at least two color encoding regions having different colors.

In one embodiment, the color encoding regions have different lengths.

In one embodiment, the multiple detecting particles have a disk shape.

In one embodiment, the probe region comprises a polymeric resin forming a porous support and detection means coupled to the polymeric resin.

In one embodiment, the encoding region has a density greater than the probe region.

A method for producing a multi-detecting particle according to an embodiment of the present invention includes: preparing a first cross-linkable polymer having an acrylate group and an encoding region including a quantum dot bonded with an acrylate group and a second cross- And a probe region including a detection means, and exposing at least a part of the base film to cure the exposure region.

In one embodiment, the step of preparing the base film further comprises: providing an encoding composition comprising the first cross-linkable polymer and the quantum dot to form the encoding region; and forming the second cross-linkable polymer and the detection means And forming the probe region.

In one embodiment, the encoding composition further comprises a photopolymerization initiator, a porogen and water, wherein the first crosslinkable polymer comprises 30 to 50 wt%, the quantum dot aqueous dispersion solution contains 20 to 35 wt%, the photopolymerization initiator 1 To 10% by weight, the porogen 15% to 25% by weight, and extra water.

In one embodiment, the probe composition further comprises a photopolymerization initiator, a porogen, a buffer and water, wherein 10 to 30% by weight of the second crosslinkable polymer, 1 to 10% by weight of the photopolymerization initiator, 50% by weight of the buffer, 20 to 50% by weight of the buffer, and excess water.

In one embodiment, the first cross-linkable polymer and the second cross-linkable polymer include polyethylene glycol diacrylate.

According to the present invention, by chemically bonding the quantum dots to the polymer resin forming the porous hydrogel structure in the encoding region of the multi-detecting particle, the stability of the encoding means can be increased, and the density difference between the encoding region and the probe region The shape stability of the multiple detection particles and the ease of manufacture can be improved.

1 is a perspective view showing a multi-detecting particle according to an embodiment of the present invention.
FIG. 2 is an enlarged view of an encoding region of multiple detection particles according to an embodiment of the present invention.
FIGS. 3 and 4 are plan views illustrating multiple detection particles according to another embodiment of the present invention. FIG.
5 and 6 are plan views illustrating a method for producing multiple detection particles according to an embodiment of the present invention.
7 is an image showing the porous support of Example 1 and Comparative Example 1. Fig.
8 is an image showing the multiple detection particles of Example 2. Fig.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, multi-detecting particles including quantum dots and a method for producing the same will be described according to an embodiment of the present invention.

In this application, the terms first, second, etc. may be used to describe various elements, but the elements should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, the terms "comprises", "having", and the like are used to specify that a feature, a number, a step, an operation, an element, a part or a combination thereof is described in the specification, But do not preclude the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

The multi-detecting particle including the quantum dot

1 is a perspective view showing a multi-detecting particle according to an embodiment of the present invention. FIG. 2 is an enlarged view of an encoding region of multiple detection particles according to an embodiment of the present invention.

Referring to FIG. 1, the multiple detecting particles 100 may have a disk shape having a circular shape on a plan view. The multiple detecting particles may have a plate shape having a polygonal shape such as a rectangle or the like on another shape, for example, a plan view.

The multi-detecting particle may include an encoding region 10 and a probe region 20 separated in a plan view. The encoding region 10 may serve as an identification means for optically identifying detection particles for detecting different targets. The probe region 20 may be enabled as a detection means for detecting a target, i.e., combining with the target, or capturing the target.

The encoding region 10 and the probe region 20 each include a polymer resin forming a porous hydrogel support. For example, the polymer resin may form a net-like porous support, and may have a hydrophilic property to form a hydrogel. Preferably, the encoding region 10 and the probe region 20 may comprise the same polymer resin, but may have different densities.

The encoding region 10 includes quantum dots 40 coupled to the polymer resin 30 as encoding means. The quantum dots 40 may be chemically bonded to the polymer resin 30 through, for example, a covalent bond.

For example, the polymer resin 30 may include, or be formed from, a polyalkylene glycol, a polyamide, a polyurethane, or the like. Preferably, the polymer resin 30 is formed from a copolymer of polyethylene glycol, polyethylene glycol, or a salt thereof. For example, the polymer resin 30 may be formed from polyethylene glycol di (meth) acrylate. Since polyethylene glycol does not contain a highly reactive functional group, it is excellent in biocompatibility and can increase detection accuracy.

The probe region 20 includes a detection means (probe). The detection means may include those known in the art, for example, proteins, DNA, RNA, cells, viruses, carbon nanotubes, cell organelles, and the like.

 The quantum dots 40 are excited by light, thereby emitting light of a constant wavelength. The detecting particles according to an embodiment of the present invention may include a plurality of color encoding regions that emit light of different wavelengths. For example, the encoding region 10 may include a first color encoding region 12 and a second color encoding region 14 that emit light of different wavelengths.

For example, in order for the first color encoding region 12 and the second color encoding region 14 to emit light of different wavelengths, the first color encoding region 12 and the second color encoding region 14, (14) may include quantum dots made of different materials. The first color encoding region 12 and the second color encoding region 14 are made of the same material but have different sizes (diameters) because the wavelengths of emitted light may vary depending on the size of the quantum dots. . ≪ / RTI >

In another embodiment, the first color encoding region 12 and the second color encoding region 14 include the same quantum dots, and the density of the quantum dots in each region may be different.

 As shown in FIG. 1, the encoding region 10 may include five color encoding regions, but this is exemplary and the number of color encoding regions included in the encoding region 10 is not particularly limited .

In one embodiment, the color encoding regions have a shape extending in the same direction and may have different lengths. For example, it is possible to divide multi-detecting particles in a disk shape so that the color encoding region is arranged to extend in parallel with the boundary line with the probe region in a semicircle and each color encoding region is extended from one end of the disk shape to the other end , Each color encoding region has a different length, which makes it easier to distinguish each color encoding region in the optical analysis process.

The color encoded in the color encoding region can be determined by the wavelength of the light emitted by the included quantum dots. Although the number and the hue are not particularly limited, the color can be easily distinguished optically, Color is preferred. For example, each color encoding region may represent either red, green, or blue.

The encoding region 10 may include a region that does not include a quantum dot, and an area that does not include a quantum dot may represent achromatic color such as black. The achromatic region may be used as a coding means.

For example, the quantum dot is a semiconducting material that emits a specific wavelength of light, but is not limited to a specific one. For example, the quantum dot may include a Group 14-16 group compound, a Group 12-16 group compound, a Group 13-15 group compound, and the like.

For example, the Group 14 to Group 16 compounds may be selected from the group consisting of tin oxide (SnO), tin sulfide (SnS), tin selenide (SnSe), tin tin (SnTe), lead sulfide (PbS), lead selenide (PbSe) (PbTe), germanium oxide (GeO), germanium sulphide (GeS), germanium selenide (GeSe), germanium telenide (GeTe), tin selenium sulfide (SnSeS), tin selenide (SnSeTe) (PbSeTe), lead sulfide (PbSTe), tin lead sulfide (SnPbS), tin lead selenide (SnPbSe), tin lead tinide (PbSe), lead selenide Tin oxide selenide (SnPbTe), tin oxide sulphide (SnOS), tin oxide selenide (SnOSe), tin oxide tin oxide (SnOTe), germanium oxide sulphide (GeOS), germanium oxide selenide (GeOSe), germanium oxide telenide lead (SnPbSSe), tin lead selenide (SnPbSeTe), tin lead sulfide tinide (SnPbSTe), and the like.

For example, the Group 12-Group 16 compounds may be cadmium sulfide (CdS), cadmium selenide (CdSe), cadmium teleonide (CdTe), zinc sulfide (ZnS), zinc selenide (ZnSe), zinc telenide Mercury selenide (HgSe), mercury tinide (HgTe), zinc oxide (ZnO), cadmium oxide (CdO), mercury oxide (HgO), cadmium selenium sulfide (CdSeS), cadmium selenium tele (CdSeTe), cadmium sulfide telenide (CdSTe), cadmium zinc sulfide (CdZnS), cadmium zinc selenide (CdZnSe), cadmium sulfide selenide (CdSSe), cadmium zinc telenide (CdZnTe) , Cadmium mercury selenide (CdHgSe), cadmium mercury tinide (CdHgTe), zinc selenium sulfide (ZnSeS), zinc selenium telenide (ZnSeTe), zinc sulfide telenide (ZnSTe), mercury selenium sulfide (HgSeS) (HgSeTe), mercury sulfide telenide (HgSTe), mercury zinc sulfide (HgZnS), mercury zinc selenide (HgZnSe), cadmium zinc oxide (CdZnO), cadmium mercury oxide (CdHgO), zinc mercury oxide (CdSeO), cadmium sulfide oxide (CdSO), mercury selenium oxide (HgSeO), zinc selenide oxide (ZnSeO), zinc telenium oxide (ZnTeO), zinc sulfide oxide (ZnSO), cadmium selenium oxide (HgTeO), mercury sulfide oxide (HgSO), cadmium zinc selenium sulfide (CdZnSeS), cadmium zinc selenium telenide (CdZnSeTe), cadmium zinc sulfide telenide (CdZnSTe), cadmium mercury selenium sulfide (CdHgSeS) Cadmium mercury selenide (CdHgSeTe), cadmium mercury sulfide telenide (CdHgSTe), mercury zinc selenium sulfide (HgZnSeS), mercury zinc selenide (HgZnSeTe), mercury zinc sulfide telenide (HgZnSTe), cadmium zinc selenium oxide (CdZnSeO), cadmium zinc telenium oxide (CdZnTeO), cadmium zinc sulfide oxide (CdZnSO), cadmium mercury selenium oxide (CdHgSeO) (CdHgTeO), cadmium mercury sulfide oxide (CdHgSO), zinc mercury selenium oxide (ZnHgSeO), zinc mercury telemonium oxide (ZnHgTeO), zinc mercury sulfide oxide (ZnHgSO), and the like.

For example, the Group 13-Group 15 compound may be selected from the group consisting of gallium phosphide (GaP), gallium arsenide (GaAs), gallium antimony (GaSb), gallium nitride (GaN), aluminum phosphide (AlN), aluminum antimony (AlSb), aluminum nitride (AlN), indium phosphide (InP), indium arsenide (InAs), indium antimony (InSb), indium nitride (InN), gallium phosphide Gallium arsenide nitrides (GaAsN), gallium antimonitride (GaSbN), aluminum phosphide arsenide (AlPAs), gallium arsenide nitride (GaAs), gallium arsenide nitride Aluminum phosphide antimony (AlPSb), aluminum phosphide nitride (AlPN), aluminum arsenide nitrides (AlAsN), aluminum antimony nitrides (AlSbN), indium phosphide arsenide (InPAs), indium phosphide antimony (InPSb), Aluminum gallium arsenide (AlGaAs), aluminum gallium antimony (AlGaSb), aluminum gallium arsenide (AlGaAs), aluminum gallium arsenide (AlGaAs), aluminum gallium arsenide , Aluminum gallium nitride (AlGaN), aluminum arsenide nitrides (AlAsN), aluminum antimonitride (AlSbN), indium gallium phosphide (InGaP), indium gallium arsenide (InGaAs), indium gallium antimony (InGaSb) , Indium gallium nitride (InGaN), indium arsenide nitride (InAsN), indium antimonitride (InSbN), aluminum indium phosphide (AlInP), aluminum indium arsenide (AlInAs), aluminum indium antimony , Aluminum indium nitrides (AlInN), aluminum arsenide nitrides (AlAsN), aluminum antimony nitrides (AlSbN), aluminum phosphide nitrides (AlPN), gallium arsenide (GaAlPAs), gallium aluminum phosphide antimony (GaAlPSb), gallium indium phosphide arsenide (GaInPAs), gallium indium aluminum arsenide (GaInAlAs), gallium aluminum phosphide nitride (GaAlPN), gallium aluminum (GaAlAsN), gallium aluminum antimonitride (GaAlSbN), gallium indium phosphide nitride (GaInPN), gallium indium arsenide nitride (GaInAsN), gallium indium aluminum nitride (GaInAlN), gallium antimony Gallium arsenide phosphide nitride (GaInPN), gallium arsenide phosphide nitride (GaSbPN), gallium arsenide phosphide nitride (GaAsPN), gallium arsenide antimonitride (GaAsSbN), gallium indium phosphide antimony (GaInPb), gallium indium phosphide nitride Gallium indium antimonitride (GaInSbN), gallium phosphide antimonitride (GaPSbN), indium aluminum phosphide Indium aluminum phosphide nitrides (InAlPN), indium phosphide arsenide nitrides (InPAsN), indium aluminum antimony nitrides (InAlSbN), indium phosphide antimony nitrides (InPSbN), indium aluminum phosphide nitrides (InAsSbN) and indium aluminum phosphide antimony (InAlPSb), and the like.

The quantum dot may have a diameter of about 1 to 100 nm, and preferably a diameter of about 1 to 20 nm.

FIGS. 3 and 4 are plan views illustrating multiple detection particles according to another embodiment of the present invention. FIG.

Referring to FIG. 3, in the encoding region 210 of the multiple detecting particles 200, the first color encoding region 212 and the second color encoding region 214 may have different widths.

Referring to FIG. 4, the multi-detecting particle 300 includes an encoding region 310, a probe region 320, and a buffer region 330 disposed between the encoding region 310 and the probe region 330 can do.

The density of the polymer resin in the buffer region 330 may be greater than the density of the polymer resin in the buffer region 330. The buffer region 330 may include a polymeric resin forming a porous hydrogel support similar to the encoding region 310 and the probe region 320, The density of the polymer resin in the encoding region 310 and the probe region 320 is different. Specifically, the density of the polymer resin in the buffer region 330 has a value between the density of the polymer resin in the encoding region 310 and the density of the polymer resin in the probe region 320.

With this configuration, the buffer region 330 can prevent deformation due to the density difference between the encoding region 310 and the probe region 320. Although the buffer region 330 has been described as a separate region, it may actually be a portion of the probe region 320.

According to the above embodiments, it is possible to increase the stability of the encoding means by chemically bonding the quantum dots to the polymer resin forming the porous hydrogel structure in the encoding region of the multiple detection particles, and to improve the density of the encoding region and the probe region By reducing the difference, the shape stability of the multiple detecting particles and the ease of manufacture can be improved.

Method for producing multiple detection particles containing quantum dots

5 and 6 are plan views illustrating a method for producing multiple detection particles according to an embodiment of the present invention.

Referring to FIG. 5, there is shown an optical recording medium comprising an encoding region (ER) comprising a quantum dot bonded with an acrylate group, a crosslinkable polymer having an acrylate group and a photopolymerization initiator, a detecting means, a crosslinkable polymer having an acrylate group, Thereby forming a base film including a probe region PR in contact with the encoding region ER.

The encoding region ER may include a plurality of color encoding regions. For example, in one embodiment, the encoding region ER includes a first color encoding region ER1, a second color encoding region ER2, a third color encoding region ER3, a fourth color encoding region ER4 and a fifth color encoding region ER5.

The color encoding regions and the probe region PR may have a shape extending in a first direction and may be arranged parallel to each other along a second direction intersecting the first direction.

An encoding composition (ERC) is provided to form the encoding region (ER). Wherein the encoding composition (ERC) comprises a first color encoding composition (ERC1), a second color encoding composition (ERC2), a third color encoding composition (ERC3), a fourth color encoding composition And a fifth color encoding composition (ERC5).

In order to form the probe region PR, a probe composition (PRC) is provided.

For example, in order to form the encoding region ER and the probe region PR, the encoding composition (ERC) and the probe composition (PRC) may be provided on a plate-shaped substrate or in a tube- . The encoding composition (ERC) and the probe composition (PRC) may be provided through separate inlets, for example, simultaneously.

The base film may include a dummy area DR located outside the encoding area ER. The dummy area DR may be for securing a margin of the encoding area ER during patterning of the base film and preventing loss of the encoding area ER. To form the dummy area DR, a dummy composition DRC may be provided.

The encoding composition (ERC) includes a quantum dot bonded with an acrylate group, a crosslinkable polymer having an acrylate group, and a photopolymerization initiator. Here, the acrylate group may include a methacrylate group.

The quantum dot includes an acrylate group bonded to the surface. For example, the quantum dot can be obtained by reacting a quantum dot having an amine group bonded to its surface with acrylate-PEG-SVA, which is an acrylation linker.

< acrylate-PEG-SVA &

At least two of the first color encoding area ER1, the second color encoding area ER2, the third color encoding area ER3, the fourth color encoding area ER4 and the fifth color encoding area ER5 Includes quantum dots that emit light of different wavelengths so as to have different colors.

For example, one of the first color encoding composition (ERC1), the second color encoding composition (ERC2), the third color encoding composition (ERC3), the fourth color encoding composition (ERC4) and the fifth color encoding composition At least one may include quantum dots to have one of red, green, and blue. In addition, the first color encoding composition (ERC1), the second color encoding composition (ERC2), the third color encoding composition (ERC3), the fourth color encoding composition (ERC4) and the fifth color encoding composition , And may not include quantum dots so as to have an achromatic color.

The quantum dots are provided in a form dispersible (dissolvable) in water, and can be contained in a solution form.

The crosslinkable polymer having an acrylate group may form a crosslinked structure by an addition reaction to form a porous support. Preferably, the crosslinkable polymer has at least two acrylate groups.

For example, the crosslinkable polymer having an acrylate group may include a polymer such as polyethylene glycol, polyamide, polyurethane or a copolymer thereof. Preferably, the crosslinkable polymer having an acrylate group may include polyethylene glycol di (meth) acrylate. For example, the weight average molecular weight of the crosslinkable polymer having an acrylate group may be 300 to 3,000.

The photopolymerization initiator may be any of those capable of initiating crosslinking of the unsaturated hydrocarbon. Examples thereof include 1-hydroxycyclohexyl phenyl ketone (IRGACURE 184), bis (2,4,6-trimethyl Benzoyl) phenylphosphine oxide (IRGACURE 819), 2,4,6-trimethylbenzoyldiphenylphosphine (TPO), 2-hydroxy-2-methyl-1-phenyl-1-propane (DAROCUR 1173) And the like. These may be used alone or in combination.

The encoding composition (ERC) may further include a porogen (porogen) so that the porous support can be easily formed.

For example, the porogen may comprise a polymer. For example, the porogen may include polyethylene glycol, polyethylene oxide, polycaprolactone, polylactic acid, polyglycolic acid, polyurethane, polyvinyl alcohol, polyacrylic acid, polyamide, or copolymers thereof. Preferably, the porogen may comprise polyethylene glycol. For example, the weight average molecular weight of the porogen may be 300 to 3,000.

The encoding composition (ERC) may comprise residual water as a solvent.

For example, the encoding composition (ERC) comprises about 30 to 50 wt% of a crosslinkable polymer having an acrylate group, about 20 to 35 wt% of an aqueous dispersion solution of quantum dots bonded with an acrylate group, about 1 to 10 wt% %, About 15 to 25% by weight of porogen, and extra water (deionized water).

The probe composition (PRC) includes a detecting means, a crosslinkable polymer having an acrylate group, and a photopolymerization initiator.

The detection means may include, for example, proteins, DNA, RNA, cells, viruses, carbon nanotubes, cell organelles, and the like. The detection means may have an acrylate group so as to be capable of bonding with the crosslinkable polymer having the acrylate group.

The probe composition (PRC) may further comprise a buffer. The buffer may comprise Tris buffer, Tis-EDTA buffer, phosphate buffered saline (PBS) solution, citric acid buffer, and the like.

The probe composition (PRC) may further include a porogen.

The probe composition (PRC) may contain a residual amount of water as a solvent.

The crosslinkable polymer having an acrylate group, the photopolymerization initiator and the porogen may be the same as those used in the encoding composition (ERC), but may have a composition different from that of the encoding composition (ERC). For example, in the probe composition (PRC), the content of the crosslinkable polymer having an acrylate group may be smaller than that of the encoding composition (ERC). Relatively, the content of the porogen may be greater than in the encoding composition (ERC).

For example, the probe composition (PRC) may contain about 10 to 30% by weight of a crosslinkable polymer having an acrylate group, about 1 to 10% by weight of a photopolymerization initiator, about 30 to 50% by weight of a porogen, about 20 to 50% % And extra water (deionized water). The detection means may be included in the solution, for example, from about 5 to 15% by weight.

In another embodiment, the content of the crosslinkable polymer having an acrylate group of the probe composition (PRC) and the content of the porogen may be substantially the same as in the encoding composition (ERC).

The dummy composition (DRC) may comprise the same material as the encoding composition (ERC) except that it does not contain a quantum dot. For example, the dummy composition (DRC) may contain about 30 to 50 wt% of a crosslinkable polymer having an acrylate group, about 1 to 10 wt% of a photopolymerization initiator, about 15 to 25 wt% of a porogen, and excess water (deionized water) . &Lt; / RTI &gt;

Although not shown, the probe region PR may include a buffer region in contact with the encoding region ER. The buffer composition for forming the buffer region may comprise the same material as the probe composition (PRC) except that it does not include a detection means. For example, the buffer composition may include a crosslinkable polymer having an acrylate group, a photopolymerization initiator, a porogen, a buffer, and excess water (deionized water), and the content of the crosslinkable polymer having an acrylate group, And may have a value between the content in the encoding composition (ERC) and the content in the probe composition (PRC).

Referring to FIG. 6, light (LIGHT) such as ultraviolet light is irradiated to the base film to cure the exposure area LE.

In one embodiment, the exposure area LE may be part of the base film, but in other embodiments, the entire base film may be exposed. Therefore, the exposure area LE includes at least a part of each of the probe area PR and the encoding area ER.

When the base film is irradiated with light, a photopolymerization initiator is activated in the exposure region (LE) to generate a radical, and the radical is converted into an acrylate group of the crosslinkable polymer, an acrylate group of the quantum dot, Acrylate group and the addition reaction proceeds. The crosslinkable polymer reacts with each other to form a support having a network-like crosslinked structure. For example, when the crosslinkable resin is polyethylene glycol diacrylate, a crosslinked structure can be formed through the following reaction.

&Lt; Crosslinking reaction of polyethylene glycol diacrylate >

The acrylate group of the quantum dot or the acrylate group of the detecting means may react chemically with the crosslinkable polymer by reacting with the activated acrylate group of the crosslinkable polymer.

The porogen does not react by photopolymerization, and the space occupied by the porogen subsequently becomes void, so that a porous support can be formed.

After the curing reaction by photopolymerization, the base film is washed with deionized water, buffer solution or the like. Unreacted materials such as unreacted crosslinking polymer, unreacted quantum dots, unreacted detection means, porogen and the like are removed by washing, and the porous support of the exposure area LE remains. The porous support may comprise a chemically bonded detection means in the probe region PR, forming a hydrogel and chemically bonded quantum dots in the encoding region ER.

The porous support of the exposure area LE can be used as multiple detection particles. In one embodiment, disk-shaped particles can be obtained by adjusting the exposure area of the exposure machine or using a mask or the like so that the exposed area has a circular shape and then removing (dissolving) the remaining area through cleaning. In another embodiment, the exposure area LE may be physically repainted so that the multiple detecting particles have a desired shape or size, if necessary.

If the content of the crosslinking polymer is higher in the encoding region ER than in the probe region PR, the encoding region ER may have a density greater than that of the probe region PR. Therefore, the pores of the porous support of the encoding region ER may be smaller than the pores of the porous support of the probe region PR.

According to the present invention, by chemically bonding the quantum dots to the polymer resin forming the porous hydrogel structure in the encoding region of the multi-detecting particle, the stability of the encoding means can be increased, and the density difference between the encoding region and the probe region The shape stability of the multiple detection particles and the ease of manufacture can be improved.

Hereinafter, the constitution and the production method of the multiple detection particles according to the present invention will be described in detail with reference to specific examples and experimental examples.

Example 1

40 wt% of polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 20 wt% of polyethylene glycol (PEG600, Sigma-Aldrich) as a porogen, 5 wt% of a photoinitiator (Darocur 1173, Sigma-Aldrich) And 27.5 wt% of a quantum dot aqueous solution were prepared. The quantum dot aqueous solution contained a red quantum dot (MagQuTM-91002 Qdot-615 nm-Methacrylate, NVIGEN) combined with a methacrylate group at a concentration of 0.17 mg / ml.

A film was formed using the above composition, and a part of the film (circular spot) was exposed to ultraviolet light (365 nm, 150 ms), and then a phosphate buffer saline (PBS) solution containing 0.05 wt% of a surfactant tween- To thereby form a porous support for forming a hydrogel.

Comparative Example 1

A porous support was formed in the same manner as in Example 1, except that a red quantum dot (concentration: 0.2 mg / ml) coupled with an amine group was used instead of the red quantum dot bound to the methacrylate group.

7 is an image showing the porous support of Example 1 and Comparative Example 1. Fig.

Referring to FIG. 7, it can be seen that, in the case of the porous support of Example 1, the red color was clearly observed as compared with the porous support of Comparative Example 1. FIG. This indicates that, in Example 1 using a quantum dot bonded with a methacrylate group, the quantum dots were chemically bonded to the polymer resin of the porous support in the photopolymerization process, so that bonding was maintained even after cleaning. In Comparative Example 1, And does not react with the polymer resin, resulting in a large outflow in the cleaning step.

Example 2

40 wt% of polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 20 wt% of polyethylene glycol (PEG600, Sigma-Aldrich) as a porogen, 5 wt% of a photoinitiator (Darocur 1173, Sigma-Aldrich) And 27.5 wt% of a quantum dot aqueous solution containing a red quantum dot (MagQuTM-91002 Qdot-615nm-Methacrylate, NVIGEN) in association with a methacrylate group at a concentration of 0.17 mg / ml.

40 wt% of polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 20 wt% of polyethylene glycol (PEG600, Sigma-Aldrich) as a porogen, 5 wt% of a photoinitiator (Darocur 1173, Sigma-Aldrich) And 27.5% by weight of a quantum dot aqueous solution containing a green quantum dot (MagVigen ™ Customize-61002 GA-Qdot-535 nm-Methacrylate, NVIGEN) in combination with a methacrylate group at a concentration of 0.17 mg / ml.

40 wt% of polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 20 wt% of polyethylene glycol (PEG600, Sigma-Aldrich) as a porogen, 5 wt% of a photoinitiator (Darocur 1173, Sigma-Aldrich) And 27.5 wt% of a quantum dot aqueous solution containing a blue quantum dot (MagQuTM-91002 Qdot-460nm-Methacrylate, NVIGEN) at a concentration of 0.17 mg / ml in combination with a methacrylate group.

40 weight% polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 20 weight percent polyethylene glycol (PEG600, Sigma-Aldrich) as porogen, 5 weight percent photoinitiator (Darocur 1173, Sigma-Aldrich) % &Lt; / RTI &gt; was prepared.

20% by weight of polyethylene glycol diacrylate (PEG700DA, Sigma-Aldrich), 40% by weight of polyethylene glycol (PEG600, Sigma-Aldrich) as a porogen, 5% by weight of a photoinitiator (Darocur 1173, Sigma-Aldrich) (Sigma-Aldrich) was prepared and mixed with a 9: 1 volume of acrylated anti-acetyl histone H3K9, di-methyl histone H3K9, tri-methyl histone H3K9, The composition was prepared.

By forming the encoding region using the red-coded composition, the green-coded composition, the blue-coded composition, and the colorless coding composition and using the probe composition to form a probe region in contact with the encoding region, . (Circular spot) of the base film was exposed to ultraviolet light (365 nm, 150 ms) and then washed with a phosphate buffered saline (PBS) solution containing 0.05 wt% of a surfactant, tween-20, Thereby forming a water-soluble particle.

Further, by combining the red coding composition (R), the green coding composition (G), the blue coding composition (B) and the colorless coding composition (N) in each of the five color coding areas, Particle specimens were prepared.

8 is an image showing the multiple detection particles of Example 2. Fig.

Referring to FIG. 8, the specimens 1 (GBRBG), the specimen 2 (RGBGR), the specimen 3 (BGBRG), the specimen 4 (BRGRB), the specimen 5 (GRBGB), the specimen 6 (BGRBG) (BGRBR), GBRGB, RBRBG, NGRBG, BNGRB, PSN 13, GBRNR, and GBGRN, respectively. It is possible to clearly distinguish and recognize.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention as defined by the following claims. You will understand.

The present invention can be used for the detection of various biological elements such as proteins, viruses, cells, DNA, RNA and the like, and can be used particularly for simultaneous detection of various targets.

Claims (15)

Encoding region; And
A probe region coupled with the encoding region,
Wherein the encoding region comprises: a polymeric resin forming a porous support; And
A quantum dot chemically bonded to the polymer resin,
Wherein the encoding region includes at least two color encoding regions having different colors, and wherein the color encoding regions have different lengths. The multi-detection particle according to claim 1, wherein the polymer resin comprises a polyethylene glycol-based resin. delete delete The multi-detection particle according to claim 1, which has a disk shape. 2. The multiple detection particle according to claim 1, wherein the probe region comprises a polymer resin forming a porous support and detection means coupled to the polymer resin. Encoding region; And
A probe region coupled with the encoding region,
Wherein the encoding region comprises: a polymeric resin forming a porous support; And
A quantum dot chemically bonded to the polymer resin,
Wherein the encoding region has a density greater than the probe region. Preparing a base film comprising a first cross-linkable polymer having an acrylate group and a second cross-linkable polymer comprising an acrylate group and an encoding region including a quantum dot bonded with an acrylate group, and a probe region including detection means ; And
Exposing at least a part of the base film to cure the exposure area,
Wherein the step of preparing the base film comprises:
Providing an encoding composition comprising the first cross-linkable polymer and the quantum dot to form the encoding region; And
Providing a probe composition comprising the first cross-linking polymer, the second cross-linking polymer and the detecting means to form the probe region. delete The method according to claim 8, wherein the encoding composition further comprises a photopolymerization initiator, a porogen, and water. The method according to claim 10, wherein the encoding composition comprises 30 to 50 wt% of the first crosslinkable polymer, 20 to 35 wt% of the aqueous dispersion solution of the quantum dots, 1 to 10 wt% of the photopolymerization initiator, 15 to 25 wt% % &Lt; / RTI &gt; by weight, and an excess of water. 9. The method according to claim 8, wherein the probe composition further comprises a photopolymerization initiator, a porogen, a buffer and water. 13. The method of claim 12, wherein the probe composition comprises 10 to 30 wt% of the second crosslinkable polymer, 1 to 10 wt% of the photopolymerization initiator, 30 to 50 wt% of the porogen, 20 to 50 wt% of the buffer, Of water. &Lt; RTI ID = 0.0 &gt; 8. &lt; / RTI &gt; 9. The method according to claim 8, wherein the first crosslinkable polymer and the second crosslinkable polymer comprise polyethylene glycol diacrylate. 9. The method of claim 8, wherein the encoding region includes at least two color encoding regions having different colors.

Images