Preparation method of quantum dot fluorescent microspheres, quantum dot fluorescent microspheres and applications

Abstract

The present invention discloses a preparation method of quantum dot fluorescent microspheres, quantum dot fluorescent microspheres and applications, relating to the technical field of quantum dots. A monomer, a crosslinking agent, an initiator, quantum dots and a molecular weight regulator are mixed to obtain an oil phase mixture; after the oil phase mixture is emulsified and dispersed, it is mixed and swollen with a swollen seed microsphere mixture, and then the temperature is raised for polymerization; wherein, the monomer is the same as or a derivative of the structural unit of the seed microsphere; the molecular weight regulator is selected from at least one of thiols and thioethers. By adding thiols and / or thioethers as molecular weight regulators to the oil phase mixture, an appropriate amount of aqueous phase inhibitor is introduced to adjust the reaction rate, and the rate of entry of quantum dots and monomers / oligomers into the spheres is controlled to be quite equivalent, so as to embed more quantum dots to the greatest extent during the preparation of microspheres, and improve the fluorescence intensity of the quantum dot microspheres.

Description

Technical Field

[0001] The present invention relates to the technical field of quantum dots, and in particular, to a preparation method of quantum dot fluorescent microspheres, quantum dot fluorescent microspheres and applications thereof. Background Art

[0002] Quantum dots are a class of crystalline nanoparticles that exhibit size-dependent properties due to the quantum confinement effect of electron states. They have excellent properties such as large Stokes shift, narrow emission spectrum, and resistance to photobleaching. They can achieve single-excitation multi-emission, and there is no mutual interference between fluorescences. They are an ideal fluorescent coding material and can also achieve high-throughput detection.

[0003] Currently, there are two common methods for preparing quantum dot-coded microspheres:

[0004] (1) Method based on finished monodisperse microspheres

[0005] First, the microspheres are swollen, and hydrophobic quantum dots randomly enter the microspheres through diffusion; or amphiphilic polymers are used to mediate the embedding of quantum dots into monodisperse porous microspheres. However, the amphiphilic polymers will inevitably undergo ligand exchange with the quantum dots, resulting in a significant decrease in the photoluminescence quantum yield (PLQY) of the quantum dots and non-uniform fluorescence of each microsphere.

[0006] (2) Copolymerization method

[0007] By stirring or extruding through a ceramic membrane to form relatively uniform quantum dot-monomer droplets, and initiating-polymerizing to form quantum dot fluorescent microspheres, doping quantum dots during the synthesis of the microspheres. However, due to the poor compatibility between the quantum dots and the polymer microspheres, the quantum dot content in the quantum dot microspheres is low and the fluorescence intensity is low.

[0008] Therefore, how to increase the content of quantum dots and the fluorescence intensity of quantum dot microspheres is an urgent problem to be solved.

[0009] In view of this, the present invention is specifically proposed. Summary of the Invention

[0010] The purpose of the present invention is to provide a preparation method of quantum dot fluorescent microspheres, quantum dot fluorescent microspheres and applications thereof, aiming to increase the quantum dot content and fluorescence intensity of quantum dot microspheres.

[0011] The present invention is implemented as follows:

[0012] In a first aspect, the present invention provides a preparation method of quantum dot fluorescent microspheres, including:

[0013] Mix a monomer, a crosslinking agent, an initiator, quantum dots, and a molecular weight regulator to obtain an oil-phase mixture; after emulsifying and dispersing the oil-phase mixture, mix it with the swollen seed microsphere mixture for swelling, and then raise the temperature for polymerization; wherein, the monomer has the same structure as the structural unit of the seed microsphere or is a derivative thereof; the molecular weight regulator is selected from at least one of thiols and thioethers.

[0014] In an alternative embodiment of the present invention, the molecular weight regulator is selected from at least one of phenyl ethyl mercaptan, octyl sulfide, benzene dithiol, triphenylmethyl mercaptan, tert-dodecyl mercaptan, tert-tetradecyl mercaptan, adamantane mercaptan, diallyl disulfide, dibenzyl disulfide, and diphenyl disulfide; preferably, the molecular weight regulator is selected from at least one of phenyl ethyl mercaptan and octyl sulfide.

[0015] In an alternative embodiment of the present invention, the mass ratio of the molecular weight regulator to the quantum dots is 0.1-0.5:100;

[0016] Preferably, the volume ratio of the monomer to the crosslinking agent is 20-100:1. When the sum of the volumes of the monomer and the crosslinking agent is 100 mL, the mass of the corresponding initiator is 0.01 g-0.5 g, the mass of the corresponding molecular weight regulator is 0.2-0.5 g, and the mass of the corresponding quantum dots is 0.5-1 g.

[0017] In an alternative embodiment of the present invention, the crosslinking agent is a compound containing at least two vinyl groups;

[0018] Preferably, the crosslinking agent is selected from at least one of divinylbenzene, allyl ether, diethyl diallylmalonate, diallyl disulfide, ethylene glycol diacrylate, ethylene glycol dimethacrylate, 1,3-propanediol diacrylate, 1,3-propanediol dimethacrylate, 1,3-butanediol diacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol diacrylate, and 1,4-butanediol dimethacrylate.

[0019] In an alternative embodiment of the present invention, the quantum dots refer to quantum dots with polymerizable ligands at the end groups; preferably, the polymerizable ligands on the quantum dots are selected from at least one of polyacrylate, polyphosphate, acrylate / methacrylate-functionalized polyethylene glycol, and acrylate / methacrylate-functionalized polypropylene glycol.

[0020] In an alternative embodiment of the present invention, the preparation process of the swollen seed microsphere mixture includes: mixing a swelling agent with a first emulsifier solution for emulsification to obtain swelling agent droplets, mixing the seed microspheres with a second emulsifier solution for emulsification to obtain seed microsphere emulsions, and mixing and stirring the swelling agent droplets and the seed microsphere emulsions for 3 h-6 h;

[0021] Preferably, the seed microspheres are selected from at least one of polystyrene microspheres, polymethyl methacrylate microspheres, and glycidyl methacrylate microspheres;

[0022] Preferably, the mass ratio of the seed microspheres to the swelling agent is 1:0.5 - 4;

[0023] Preferably, the difference in solubility parameters between the swelling agent and the seed microspheres is 0 - 2.

[0024] In an alternative embodiment of the present invention, an oil - phase mixture is mixed and emulsified with a third emulsifier solution to obtain mixed liquid droplets. The mixed liquid droplets are mixed with the swollen seed microsphere mixture and swollen for 3 h - 6 h to obtain a liquid to be reacted. The liquid to be reacted is mixed with a dispersant solution and then subjected to temperature - rising polymerization;

[0025] Preferably, the polymerization temperature is 60°C - 80°C, and the polymerization time is 12 h - 20 h

[0026] Preferably, the mass ratio of the seed microspheres to the monomer is 1:2 - 20;

[0027] Preferably, the dispersant solution is selected from at least one of aqueous solutions of polyvinyl alcohol, hydroxypropyl cellulose, and sodium carboxymethyl cellulose; the mass fraction of the dispersant solution is 1 - 3%, and the volume ratio of the dispersant solution to the liquid to be reacted is 10 - 20:1.

[0028] In an alternative embodiment of the present invention, the first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each independently selected from at least one of sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, and sodium oleate;

[0029] Preferably, the mass fractions of the first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each 0.1% - 0.5%, and the dosages of the first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each controlled such that the mass ratio to the material to be emulsified is 10 - 100:1.

[0030] Second, the present invention also provides a quantum dot fluorescent microsphere prepared by the preparation method in any of the above - mentioned embodiments.

[0031] Third, the present invention also provides the application of the quantum dot fluorescent microsphere in the above - mentioned embodiment in quantitative detection.

[0032] The present invention has the following beneficial effects: By adding thiol and / or thioether as a molecular weight regulator to the oil - phase mixture, introducing an appropriate amount of water - phase polymerization inhibitor to adjust the reaction rate, and controlling the rate of quantum dots and monomer / oligomer entering the sphere to be equivalent, more quantum dots are embedded during the preparation of microspheres to the greatest extent, enhancing the fluorescence intensity of the quantum dot microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.

[0034] Figure 1 SEM image of the quantum dot microspheres prepared in Example 1;

[0035] Figure 2 SEM image of the quantum dot microspheres prepared in Example 2;

[0036] Figure 3 SEM image of the quantum dot microspheres prepared in Comparative Example 1;

[0037] Figure 4 Fluorescence intensity test results of the quantum dot microspheres prepared in Example 1 and Comparative Example 1;

[0038] Figure 5 Fluorescence intensity test results of the quantum dot microspheres prepared in Example 2;

[0039] Figure 6 Electron microscopy image of the product prepared in Comparative Example 2;

[0040] Figure 7 Electron microscopy image of the product prepared in Comparative Example 3. Specific embodiments

[0041] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are followed. For the reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0042] The embodiments of the present invention provide a method for preparing quantum dot fluorescent microspheres, including the following steps:

[0043] S1. Prepare a swollen seed microsphere mixture

[0044] Mix and emulsify the swelling agent with the first emulsifier solution to obtain swelling agent droplets, mix and emulsify the seed microspheres with the second emulsifier solution to obtain a seed microsphere emulsion, and mix and stir the swelling agent droplets and the seed microsphere emulsion for 3 h - 6 h (such as 3 h, 4 h, 5 h, 6 h, etc.). First, emulsify the swelling agent and the seed microspheres, and then perform swelling, so that the seed microspheres can be fully swollen, which is beneficial to further improving the loading amount of quantum dots.

[0045] In some embodiments, the seed microspheres are selected from at least one of polystyrene microspheres, polymethyl methacrylate microspheres, and glycidyl methacrylate microspheres, and can be any one or several of the above. The difference between the solubility parameter of the swelling agent and that of the seed microspheres is 0-2. That is to say, the swelling agent refers to a solvent whose solubility parameter differs from that of the seed microspheres by less than or equal to 2.

[0046] Specifically, when the seed microspheres are polystyrene microspheres, the solubility parameter is 17.8-18.6, and the swelling agent includes but is not limited to cyclohexane, chloroethane, trichloroethane, amyl acetate, butyl acetate, o-xylene, chloroform, dibutyl phthalate, etc.; when the seed microspheres are methyl methacrylate seed microspheres, the solubility parameter is 18.4-19.4, and the swelling agent includes but is not limited to butyl acetate, carbon tetrachloride, n-propylbenzene, p-xylene, toluene, tetrachloroethylene, ethyl benzoate, chloroform, dichloromethane, etc.

[0047] It should be noted that the above several kinds of seed microspheres can be commercially available raw materials or can be synthesized independently. The synthesis method can refer to Journal of Polymer Science Part A: Polymer Chemistry (1986) 24(11) 2995-3007.

[0048] In some embodiments, the mass ratio of the seed microspheres to the swelling agent is 1:0.5-4, such as 1:0.5, 1:1.0, 1:2.0, 1:3.0, 1:4.0, etc.

[0049] In some embodiments, the first emulsifier solution and the second emulsifier solution are each independently selected from at least one of sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, and sodium oleate, and can be any one or several of the above. The mass fractions of the first emulsifier solution and the second emulsifier solution are both 0.1%-0.5%. The dosages of the first emulsifier solution and the second emulsifier solution are both controlled such that the mass ratio to the material to be emulsified is 10-100:1 to ensure sufficient emulsification.

[0050] Specifically, the mass fractions of the first emulsifier solution and the second emulsifier solution can each independently be 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, etc. The mass ratio of the dosage of the first emulsifier solution to the swelling agent can be 10:1, 30:1, 50:1, 80:1, 100:1, etc. The mass ratio of the second emulsifier solution to the seed microspheres can be 10:1, 30:1, 50:1, 80:1, 100:1, etc.

[0051] S2. Prepare the oil-phase mixture

[0052] Mix a monomer, a crosslinking agent, an initiator, quantum dots, and a molecular weight regulator to obtain an oil-phase mixture. The molecular weight regulator is selected from at least one of thiols and thioethers. By introducing the molecular weight regulator, the rate of entry of the quantum dots and the monomer / oligomer into the sphere can be made comparable, and more quantum dots can be embedded during the preparation of the microspheres to the greatest extent, enhancing the fluorescence intensity of the quantum dot microspheres.

[0053] The monomer has the same structure as the structural unit of the seed microspheres or is a derivative thereof. For example, if the seed microspheres are polystyrene microspheres, the monomer includes, but is not limited to, styrene, methylstyrene, fluorostyrene, chlorostyrene, bromostyrene, iodostyrene, and isomers thereof; if the seed microspheres are polymethyl methacrylate microspheres, the monomer includes, but is not limited to, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, glycidyl methacrylate, etc.

[0054] The crosslinking agent is a compound containing at least two vinyl groups, which is used to slow down the change in the solubility parameter and improve the compatibility between the quantum dots and the polymer. In some embodiments, the crosslinking agent is selected from at least one of divinylbenzene, allyl ether, diethyl diallylmalonate, diallyl disulfide, ethylene glycol diacrylate, ethylene glycol dimethacrylate, 1,3-propanediol diacrylate, 1,3-propanediol dimethacrylate, 1,3-butanediol diacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol diacrylate, and 1,4-butanediol dimethacrylate, and can be any one or several of the above.

[0055] The type of the initiator is not limited and can be a conventional type of initiator, such as azo initiators, peroxide initiators, etc., such as azobisisobutyronitrile, sodium persulfate, etc.

[0056] The quantum dots refer to quantum dots with polymerizable ligands at the end groups to improve the compatibility between the quantum dots and the polymer microspheres. In some embodiments, the polymerizable ligands on the quantum dots are selected from at least one of polyacrylate, polyphosphate, acrylate / methacrylate-functionalized polyethylene glycol, and acrylate / methacrylate-functionalized polypropylene glycol, and can have any one or several of the above polymerizable ligands. Specifically, the quantum dots can be at least one of II-VI group quantum dots, II-V group quantum dots, III-V group quantum dots, IV-VI group quantum dots, I-VI group quantum dots, I-III-VI group quantum dots, and IV group quantum dots, such as II-VI group Zn(S,Se), Cd(S,Se,Te), II-V group Cd3(P,As)2, III-V group In(P,As), IV-VI group Pb(S,Se), I-VI group Ag2(S,Se), I-III-VI group CuIn(S,Se)2, AgIn(S,Se)2, and IV group (C, Si, Ge), etc.

[0057] It should be noted that acrylate / methacrylate-functionalized polyethylene glycol refers to the product obtained by modifying polyethylene glycol with acrylate or methacrylate. It can be a commercially available raw material or synthesized independently. For example, the preparation method of acrylate / methacrylate-functionalized polyethylene glycol is as follows:

[0058] Using polyethylene glycol and acrylic acid as raw materials, an esterification reaction is carried out in toluene, and polyethylene glycol acrylate monoester is obtained by column chromatography separation. Then the product is mixed with maleic anhydride and heated to carry out a secondary esterification reaction, and acrylate / methacrylate-functionalized polyethylene glycol is obtained by column separation.

[0059] Similarly, methacrylate-functionalized polyethylene glycol and acrylate / methacrylate-functionalized polypropylene glycol can be obtained.

[0060] Since thiols and thioethers can undergo ligand exchange with the surface of quantum dots, in order to slow down this process, the thiol should have a certain steric hindrance to ensure that rapid ligand exchange does not occur within a short time during the preparation of the oil-phase mixture, resulting in the sedimentation of quantum dots in the oil-phase mixture. Thiols and thioethers with polycyclic or branched-chain structures can be selected. In some embodiments, the molecular weight regulator is selected from at least one of phenylethyl mercaptan, octyl sulfide, benzenedithiol, triphenylmethyl mercaptan, tert-dodecyl mercaptan, tert-tetradecyl mercaptan, adamantane mercaptan, dithiodifurfuryl, dibenzyldisulfide, and diphenyldisulfide; preferably, the molecular weight regulator is selected from at least one of phenylethyl mercaptan and octyl sulfide. The above several raw materials are all suitable for being introduced as molecular weight regulators, and all are beneficial to controlling the rate of quantum dots and monomers / oligomers entering the sphere to be quite the same, and embedding more quantum dots during the preparation of microspheres to the greatest extent, thereby enhancing the fluorescence intensity of the quantum dot microspheres.

[0061] The inventors optimized the amounts of each raw material to better control the polymerization reaction rate and obtain a uniform product: the mass ratio of the molecular weight regulator to the quantum dots is 0.1 - 0.5:100, the volume ratio of the monomer to the crosslinking agent is 20 - 100:1. When the sum of the volumes of the monomer and the crosslinking agent is 100 mL, the mass of the corresponding initiator is 0.01 g - 0.5 g, the mass of the corresponding molecular weight regulator is 0.2 - 0.5 g, and the mass of the corresponding quantum dots is 0.5 - 1 g.

[0062] Specifically, the mass ratio of the molecular weight regulator to the quantum dots can be 0.1:100, 0.2:100, 0.3:100, 0.4:100, 0.5:100, etc., and the volume ratio of the monomer to the crosslinking agent can be 20:1, 50:1, 80:1, 100:1, etc. When the sum of the volumes of the monomer and the crosslinking agent is 100 mL, the mass of the initiator can be 0.01 g, 0.05 g, 0.10 g, 0.20 g, 0.30 g, 0.40 g, 0.50 g, etc., the mass of the molecular weight regulator can be 0.2 g, 0.3 g, 0.4 g, 0.5 g, etc., and the mass of the quantum dots can be 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1.0 g, etc.

[0063] S3. Polymerization

[0064] After emulsifying and dispersing the oil-phase mixture, it is mixed and swollen with the swollen seed microsphere mixture, and then the temperature is raised for polymerization to obtain quantum dot microspheres.

[0065] In the actual operation process, the oil-phase mixture is mixed and emulsified with the third emulsifier solution to obtain mixed liquid droplets. The mixed liquid droplets are mixed and swollen with the swollen seed microsphere mixture for 3 h - 6 h to obtain a reaction solution to be reacted. The reaction solution to be reacted is mixed with the dispersant solution and then the temperature is raised for polymerization to obtain uniform quantum dot microspheres.

[0066] In some embodiments, the third emulsifier solution is selected from at least one of sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, and sodium oleate, and can be any one or several of the above. The mass fraction of the third emulsifier solution is 0.1% - 0.5% (such as 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, etc.), and the dosage of the third emulsifier solution is controlled such that the mass ratio to the material to be emulsified (i.e., the oil-phase mixture) is 10 - 100:1, such as 10:1, 30:1, 50:1, 80:1, 100:1, etc. The oil-phase mixture is ultrasonically emulsified by the third emulsifier solution and dispersed into small liquid droplets to promote the full progress of the polymerization reaction and make the obtained product more uniform.

[0067] The dosage ratio of the mixed liquid droplets to the swollen seed microsphere mixture is controlled such that the mass ratio of the seed microspheres to the monomer is 1:2 - 20.

[0068] In some embodiments, the dispersant solution is selected from at least one of an aqueous solution of polyvinyl alcohol, an aqueous solution of hydroxypropyl cellulose, and an aqueous solution of sodium carboxymethyl cellulose, and can be any one or several of the above. The mass fraction of the dispersant solution is 1-3%, and the volume ratio of the dispersant solution to the solution to be reacted is 10-20:1. By introducing the dispersant, the raw materials in the reaction system are uniformly dispersed, making the obtained quantum dot microspheres more uniform. The mass fraction of the dispersant solution can be 1%, 2%, 3%, etc., and the volume ratio of the dispersant solution to the solution to be reacted can be 10:1, 13:1, 15:1, 18:1, 20:1, etc.

[0069] In some embodiments, the polymerization temperature is 60°C - 80°C, and the polymerization time is 12h - 20h. It is appropriate to carry out the reaction within this polymerization temperature range to make the reaction rate more suitable. Specifically, the polymerization temperature can be 60°C, 70°C, 80°C, etc., and the polymerization time can be 12h, 15h, 18h, 20h, etc.

[0070] The embodiment of the present invention also provides a quantum dot fluorescent microsphere, which is prepared by the preparation method in any of the above embodiments, has the characteristic of high fluorescence intensity, can be further applied in quantitative detection, and can improve the accuracy of detection.

[0071] The features and properties of the present invention will be further described in detail below in conjunction with embodiments.

[0072] Example 1

[0073] This example provides a preparation method of a quantum dot fluorescent microsphere, including the following steps:

[0074] (1) Disperse 0.5 g of 4.5 μm polystyrene seed microspheres in 50 mL of 0.1% (m / m) sodium dodecyl sulfate aqueous solution, and ultrasonically disperse evenly.

[0075] (2) Add 2 g of cyclohexane to 50 mL of 0.1% (m / m) sodium dodecyl sulfate aqueous solution, and ultrasonically emulsify to form swelling agent droplets.

[0076] (3) Mix the two solutions obtained in step (1) and step (2) evenly, and continuously stir for 4 h to obtain a swollen seed microsphere mixture.

[0077] (4) Take 5 mL of styrene, 0.25 mL of divinylbenzene, 0.026 g of azobisisobutyronitrile, 0.02625 g of phenylethyl mercaptan, and 0.0525 g of quantum dots, mix evenly, and ultrasonically emulsify with 50 mL of 0.1% (m / m) sodium dodecyl sulfate aqueous solution to form a mixed liquid droplet.

[0078] (5) Add the mixed solution obtained in step (4) dropwise into the seeded microsphere mixed solution obtained in step (3), continue stirring for 4 h, add 10 mL of an aqueous solution of 2% (by mass) polyvinyl alcohol, raise the temperature to 70 °C, and polymerize for 16 h.

[0079] (6) Filter and resuspend to obtain the quantum dot microspheres.

[0080] Test the SEM image of the quantum dot microspheres prepared in this example. The results are as Figure 1 shown. It can be seen that the diameter of the quantum dot microspheres is about 5.0 μm and the size is uniform.

[0081] Example 2

[0082] This example provides a method for preparing quantum dot fluorescent microspheres, including the following steps:

[0083] (1) Disperse 0.5 g of 4.5-μm polymethyl methacrylate seeded microspheres in 50 mL of a 0.5% (m / m) aqueous solution of sodium dodecyl sulfate, and ultrasonically disperse evenly.

[0084] (2) Add 2 g of cyclohexane to 50 mL of a 0.5% (m / m) aqueous solution of sodium dodecyl sulfate, and ultrasonically emulsify to form swelling agent droplets.

[0085] (3) Mix the two solutions obtained in steps (1) and (2) evenly, and continuously stir for 4 h to obtain a swollen seeded microsphere mixed solution.

[0086] (4) Take 5 mL of methyl methacrylate, 0.05 mL of ethylene glycol acrylate, 0.505 mg of azodiisooctanenitrile, 0.025 g of octyl sulfide, and 0.05 g of quantum dots, mix evenly, and ultrasonically emulsify with 50 mL of a 0.5% (m / m) aqueous solution of sodium dodecyl sulfate to form a mixed solution droplet.

[0087] (5) Add the mixed solution droplet obtained in step (4) dropwise into the seeded microsphere mixed solution obtained in step (3), continue stirring for 4 h, add 10 mL of an aqueous solution of 2% hydroxypropyl cellulose, raise the temperature to 70 °C, and polymerize for 16 h.

[0088] (6) Filter and resuspend to obtain the quantum dot microspheres.

[0089] Test the SEM image of the quantum dot microspheres prepared in this example. The results are as Figure 2 shown. It can be seen that the diameter of the quantum dot microspheres is about 5.0 μm and the size is uniform.

[0090] Comparative Example 1

[0091] This comparative example provides a method for preparing quantum dot fluorescent microspheres, which is only different from Example 1 in that: in step (4), phenyl ethyl mercaptan is not added.

[0092] The SEM image of the quantum dot microspheres prepared in this comparative example was tested, and the results are as Figure 3 shown. It can be seen that the diameter of the quantum dot microspheres is about 5.2 μm. As Figure 3 shown by the arrow, when thiol is not used, the monomer grows faster on the seed microspheres. The arrow indicates the polymer formed by the quantum dots and the monomer. The growth of the quantum dot / monomer is slow, and some of them will nucleate by themselves, generating flaky and massive irregular polymers, resulting in waste of quantum dots.

[0093] The flow cytometry fluorescence images (equal mass microspheres) of the quantum dot microspheres prepared in the examples and comparative examples were tested, and the results are as Figure 4 and Figure 5 shown.

[0094] From Figure 4 it can be seen that the fluorescence intensity of Comparative Example 1 is significantly weaker than that of Example 1, and the distribution is slightly wider.

[0095] The flow cytometry fluorescence distribution of Example 2 is as Figure 5 shown. It can be seen that the distribution is narrow and concentrated, indicating that the obtained quantum dot microspheres have uniform fluorescence.

[0096] Comparative Example 2

[0097] This comparative example provides a method for preparing quantum dot fluorescent microspheres, which is only different from Example 1 in that: the amount of phenyl ethyl mercaptan in step (4) is 0.25 g.

[0098] The electron microscopy image of the product prepared in Comparative Example 2 is as Figure 6 shown. It can be seen that too much thiol is used, resulting in too small a molecular weight of the generated polystyrene, and the spheres are adhered to each other.

[0099] Comparative Example 3

[0100] This comparative example provides a method for preparing quantum dot fluorescent microspheres, which is only different from Example 1 in that: the amount of styrene in step (4) is 25 g.

[0101] The electron microscopy image of the product prepared in Comparative Example 3 is as Figure 7 shown. It can be seen that too much monomer is used, and most of the monomers spontaneously nucleate to form irregular polymers.

[0102] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of quantum dot fluorescent microspheres, characterized in that, Comprising: Mixing a monomer, a crosslinking agent, an initiator, quantum dots, and a molecular weight regulator to obtain an oil-phase mixture; After emulsifying and dispersing the oil-phase mixture, mixing it with a swollen seed microsphere mixture solution for swelling, and then raising the temperature for polymerization; Wherein, the monomer has the same structure as the structural unit of the seed microsphere or is a derivative thereof; The molecular weight regulator is selected from at least one of phenyl ethyl mercaptan, octyl thioether, benzene dithiol, triphenylmethyl mercaptan, tert-dodecyl mercaptan, tert-tetradecyl mercaptan, adamantane mercaptan, diallyl disulfide, dibenzyl disulfide, and diphenyl disulfide; The volume ratio of the monomer to the crosslinking agent is 20 - 100:

1. When the sum of the volumes of the monomer and the crosslinking agent is 100 mL, the mass of the corresponding initiator is 0.01 g - 0.5 g, the mass of the corresponding molecular weight regulator is 0.2 - 0.5 g, and the mass of the corresponding quantum dots is 0.5 - 1 g.

2. The preparation method according to claim 1, characterized in that, The molecular weight regulator is selected from at least one of phenyl ethyl mercaptan and octyl thioether.

3. The preparation method according to claim 1, wherein The crosslinking agent is a compound containing at least two vinyl groups.

4. The preparation method according to claim 3, wherein The crosslinking agent is selected from at least one of divinylbenzene, allyl ether, diethyl allylmalonate, diallyl disulfide, ethylene glycol diacrylate, ethylene glycol dimethacrylate, 1,3-propanediol diacrylate, 1,3-propanediol dimethacrylate, 1,3-butanediol diacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol diacrylate, and 1,4-butanediol dimethacrylate.

5. The preparation method according to claim 1, characterized in that, The quantum dots refer to quantum dots with polymerizable ligands at the end groups.

6. The preparation method according to claim 5, characterized in that, The polymerizable ligands on the quantum dots are selected from at least one of polyacrylate, polyphosphate, acrylate / methacrylate-functionalized polyethylene glycol, and acrylate / methacrylate-functionalized polypropylene glycol.

7. The preparation method according to claim 1, characterized in that, The preparation process of the swollen seed microsphere mixture solution includes: mixing a swelling agent with a first emulsifier solution for emulsification to obtain swelling agent droplets, mixing the seed microspheres with a second emulsifier solution for emulsification to obtain seed microsphere emulsions, and mixing and stirring the swelling agent droplets and the seed microsphere emulsions for 3 h - 6 h.

8. The preparation method according to claim 7, wherein The seed microspheres are selected from at least one of polystyrene microspheres, polymethyl methacrylate microspheres, and glycidyl methacrylate microspheres.

9. The preparation method according to claim 8, characterized in that, The mass ratio of the seed microspheres to the swelling agent is 1:0.5 - 4.

10. The preparation method according to claim 9, characterized in that, The difference in solubility parameters between the swelling agent and the seed microspheres is 0 - 2.

11. The preparation method according to claim 7, wherein, After emulsifying and mixing the oil-phase mixture with a third emulsifier solution to obtain mixed droplets, mixing the mixed droplets with the swollen seed microsphere mixture solution for swelling for 3 h - 6 h to obtain a reaction solution to be treated, and mixing the reaction solution to be treated with a dispersant solution and then raising the temperature for polymerization.

12. The preparation method according to claim 11, characterized in that, The polymerization temperature is 60°C - 80°C, and the polymerization time is 12 h - 20 h.

13. The preparation method according to claim 11, characterized in that, The mass ratio of the seed microspheres to the monomer is 1:2 - 20.

14. The preparation method according to claim 11, wherein, The dispersant solution is selected from at least one of an aqueous solution of polyvinyl alcohol, an aqueous solution of hydroxypropyl cellulose, and an aqueous solution of sodium carboxymethyl cellulose; the mass fraction of the dispersant solution is 1 - 3%, and the volume ratio of the dispersant solution to the reaction solution to be treated is 10 - 20:

1.

15. The preparation method according to claim 11, wherein The first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each independently selected from at least one of sodium dodecyl sulfonate, sodium dodecylbenzenesulfonate, and sodium oleate.

16. The preparation method according to claim 15, characterized in that, The mass fractions of the first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each 0.1%-0.5%, and the dosages of the first emulsifier solution, the second emulsifier solution, and the third emulsifier solution are each controlled such that the mass ratio to the material to be emulsified is 10-100:

1.

17. A quantum dot fluorescent microsphere, characterized in that, It is prepared by the preparation method described in any one of claims 1-16.

18. Use of the quantum dot fluorescent microspheres according to claim 17 in quantitative detection.

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