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CN118307702B - Nanometer-sized uniform-particle-size colored latex microsphere and preparation method and application thereof - Google Patents

Nanometer-sized uniform-particle-size colored latex microsphere and preparation method and application thereof Download PDF

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CN118307702B
CN118307702B CN202410719422.8A CN202410719422A CN118307702B CN 118307702 B CN118307702 B CN 118307702B CN 202410719422 A CN202410719422 A CN 202410719422A CN 118307702 B CN118307702 B CN 118307702B
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latex microsphere
acrylic acid
glycidyl methacrylate
styrene
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吴军林
郭诗静
胡霏
彭运平
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Guangzhou Wanfu Health Technology Co ltd
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Abstract

The invention provides a nano-grade uniform-particle-size colored latex microsphere, a preparation method and application thereof, wherein the preparation method of the nano-grade uniform-particle-size colored latex microsphere comprises the steps of preparing polystyrene latex microsphere emulsion by soap-free emulsion polymerization and dyeing the polystyrene latex microsphere emulsion twice; poly (styrene-acrylic acid-glycidyl methacrylate) latex microspheres are obtained by adding acrylic acid and glycidyl methacrylate in a specific ratio into polystyrene latex microspheres, and a reactive dye secondary dyeing mode is adopted, so that the finally obtained colored latex microspheres have smaller particle size (less than 250 nm), better particle size uniformity (CV value less than 5%) and good dye uptake (more than or equal to 90%). The color latex microsphere prepared by the invention can be used as a marker in immunochromatography.

Description

Nanometer-sized uniform-particle-size colored latex microsphere and preparation method and application thereof
Technical Field
The invention belongs to the technical field of nano material preparation and biological detection, and in particular relates to a preparation method of a nano-sized color latex microsphere with uniform particle size and application of the nano-sized color latex microsphere in an immunochromatography technology.
Background
The color latex microsphere as a multifunctional nano material has wide application prospect in the fields of biological detection, protein marking, medical clinical diagnosis and the like due to the unique particle size, color and surface characteristics. The main characteristics of the color latex microsphere include customizable particle size (usually between nanometer level and micrometer level), bright color, high contrast, high uniformity of particle size (CV% is less than 5%), small difference between batches, good repeatability and the like. In addition, the surface of the color latex microsphere is easy to carry out various chemical modifications, and different biomolecules such as antibodies, antigens, nucleic acids and the like can be connected, so that the high-sensitivity and specificity detection of the specific biomolecules is realized.
In the prior art, the preparation method of the color latex microsphere mainly comprises a copolymerization method, an embedding method and a surface modification method. However, these methods have respective disadvantages in preparing color latex microspheres of uniform particle size at a nanometer level.
Copolymerization method: the copolymerization method is to directly copolymerize dye molecules and monomers in a polymerization reaction to enable the dye molecules to be embedded into polymer chains, so as to prepare the color latex microspheres. The color latex microsphere prepared by the method has bright color, but the distribution of dye molecules is not easy to control, the color is easy to be uneven, the stability of the dye in the polymer is poor, and leakage is easy to occur. In addition, the color latex microspheres prepared by the copolymerization method have poor monodispersity and wide particle size distribution, are difficult to prepare the color latex microspheres with uniform particle size, have complex preparation process and higher cost.
Embedding method: the embedding method is to prepare the color latex microspheres by physically embedding dye molecules inside the polymer microspheres. The color latex microsphere prepared by the method has stable color, but the embedding process is difficult to control, the embedding efficiency is low, and the embedded dye molecules are easy to leak in subsequent treatment.
Surface modification method: the surface modification method is to prepare the color latex microsphere by connecting dye molecules on the surface of the prepared polymer microsphere in a chemical bonding, physical adsorption and other modes. The color latex microsphere prepared by the method has stable color and the surface is easy to carry out functional modification. However, the surface modification method requires the preparation of polymer microspheres in advance, is limited by the number and density of surface functional groups, and is not easy to control the distribution of dye molecules on the surfaces of the microspheres, and is also easy to cause uneven color.
Therefore, aiming at the problems in the prior art, a novel method for preparing the nano-sized color latex microspheres with uniform particle size is developed to overcome the defects of the prior art, and has important research significance and practical application value.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention aims to provide a preparation method of nano-sized uniform-particle-size colored latex microspheres, which aims to solve the technical problems of non-uniform particle size, poor monodispersity, low dyeing efficiency and the like in the existing preparation method of the colored latex microspheres.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
s1, preparing polystyrene latex microsphere emulsion by soap-free emulsion polymerization;
S2, dissolving a certain amount of water-soluble dye in a certain amount of deionized water, adding the water-soluble dye into the polystyrene latex microsphere emulsion in batches and time by a sectional heating method, and stirring and reacting for a certain time to obtain a colored polystyrene latex microsphere emulsion A after primary dyeing;
s3, adding ethylenediamine into the color polystyrene latex microsphere emulsion A, and heating and reacting for a certain time to obtain surface amino color polystyrene latex microsphere emulsion B;
s4, dissolving a certain amount of water-soluble dye in a certain amount of deionized water, adding the deionized water into the surface-aminated color polystyrene latex microsphere emulsion B, heating and reacting for a certain time at a certain temperature, and washing with the deionized water after the reaction is finished to obtain the nanoscale color latex microsphere with uniform particle size.
Preferably, the polystyrene latex microsphere emulsion in the step S1 is poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion, and the preparation process is as follows:
Introducing nitrogen into a three-neck flask containing a certain amount of deionized water, adding a certain amount of initiator, stirring uniformly, then dropwise adding a mixed solution of styrene, acrylic acid and glycidyl methacrylate, heating to 70-90 ℃ after the dropwise adding is finished, keeping the reaction for 2-5h, and cooling to room temperature to obtain the white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion with carboxyl and epoxy groups modified on the surface.
Preferably, the initiator is selected from potassium persulfate or ammonium persulfate;
Preferably, the mass ratio of the styrene, the acrylic acid and the glycidyl methacrylate to the initiator is 100: (0.5-2);
preferably, the mass ratio of the styrene to the (acrylic acid+glycidyl methacrylate) is (5-15): 1, a step of; the mass ratio of the acrylic acid to the glycidyl methacrylate is (1-3): 1, a step of;
Preferably, the water-soluble dye in step S2 is selected from fluorescein isothiocyanate or tetramethylrhodamine isothiocyanate;
The mass ratio of the water-soluble dye to the deionized water is (3-6): 1, a step of; the sectional heating method is added in batches and time-by-time specifically comprises the following steps: the water-soluble dye dissolved in deionized water is divided into three parts, and then added into polystyrene latex microsphere emulsion at 80 ℃ to react for 2 hours, then heated to 100 ℃ to react for 2 hours, and then heated to 120 ℃ to react for 2 hours.
Preferably, the addition amount of ethylenediamine in the step S3 is 2 to 3 times that of (acrylic acid+glycidyl methacrylate); the heating reaction temperature is 80 ℃ and the reaction time is 12-24 hours;
preferably, the mass ratio of the water-soluble dye to the deionized water in the step S4 is (3-6): 1, the heating temperature is 60-80 ℃ and the reaction time is 12-15h.
Preferably, the mass ratio of the styrene to the water-soluble dye is 10: (0.1-3).
The second object of the present invention is to provide a colored latex microsphere obtained by the above-mentioned method for producing a colored latex microsphere having a uniform particle diameter at a nanometer level.
The particle size of the color latex microsphere is less than 250nm, the CV value of particle size uniformity is less than 5%, and the dye-uptake is more than or equal to 90%.
The third object of the present invention is to provide an application of the color latex microsphere obtained by the preparation method of the color latex microsphere with uniform particle size in immunochromatography as a marker.
Compared with the prior art, the invention has the following advantages:
(1) According to the invention, the specific proportion of acrylic acid and glycidyl methacrylate are creatively added into the polystyrene latex microsphere to obtain the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere, and the acrylic acid and the glycidyl methacrylate are matched in a synergistic manner through different hydrophilic solubilities of the acrylic acid and the glycidyl methacrylate, so that the precipitation rate of the microsphere is controlled in the polymerization process, and the technical effect of adjusting the particle size and uniformity of the microsphere is achieved.
(2) The invention creatively adopts a secondary dyeing mode, wherein the dye is coated inside the polymer microsphere as much as possible by adopting a sectional heating mode in the primary dyeing mode, and the secondary dyeing plays a good covalent bonding role through the reaction of the functional group of the dye and the amino on the surface of the microsphere, so that the finally obtained color latex microsphere has smaller particle size (less than 250 nm), better particle size uniformity (CV value less than 5%) and good dye uptake (more than or equal to 90%).
Detailed Description
The raw materials and equipment used in the invention are common raw materials and equipment in the field unless specified otherwise; the methods used in the present invention are conventional in the art unless otherwise specified.
Unless otherwise defined, all terms used in the specification have the same meaning as commonly understood by one of ordinary skill in the art, but are defined in the specification to be used in the event of a conflict.
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
Example 1
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 3g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into trisections, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours at 80 ℃, then heating to 100 ℃, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours, heating to 120 ℃, and adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours to obtain colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere with nano-scale and uniform particle size is obtained.
Example 2
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 2g of acrylic acid and 2g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into trisections, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours at 80 ℃, then heating to 100 ℃, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours, heating to 120 ℃, and adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours to obtain colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere with nano-scale and uniform particle size is obtained.
Example 3
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 1g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into trisections, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours at 80 ℃, then heating to 100 ℃, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours, heating to 120 ℃, and adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours to obtain colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere with nano-scale and uniform particle size is obtained.
Example 4
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 3g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye fluorescein isothiocyanate in 100mL of deionized water, dividing into three equal parts, adding the water-soluble dye fluorescein isothiocyanate into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion at 80 ℃ for reaction for 2 hours, heating to 100 ℃ for reaction for 2 hours, adding the water-soluble dye fluorescein isothiocyanate into the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion, heating to 120 ℃ for reaction for 2 hours, and obtaining color polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye fluorescein isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface aminated color polystyrene latex microsphere emulsion B to be heated and reacted for 15 hours at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the nanoscale yellow-green latex microsphere with uniform particle size is obtained.
Comparative example 1
The preparation method of the color latex microsphere comprises the following preparation steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene and 4g of acrylic acid, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into three equal parts, adding the water-soluble dye tetramethylrhodamine isothiocyanate into poly (styrene-acrylic acid) latex microsphere emulsion at 80 ℃ for reaction for 2 hours, heating to 100 ℃, adding the water-soluble dye tetramethylrhodamine isothiocyanate into poly (styrene-acrylic acid) latex microsphere emulsion for reaction for 2 hours, heating to 120 ℃, adding the water-soluble dye tetramethylrhodamine into poly (styrene-acrylic acid) latex microsphere emulsion for reaction for 2 hours, and obtaining color polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere is obtained.
Comparative example 2
The preparation method of the color latex microsphere comprises the following preparation steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene and 4g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into trisections, adding the trisections into poly (styrene-glycidyl methacrylate) latex microsphere emulsion at 80 ℃ for reaction for 2 hours, heating to 100 ℃ and adding the trisections into poly (styrene-glycidyl methacrylate) latex microsphere emulsion for reaction for 2 hours, heating to 120 ℃ and adding the trisections into poly (styrene-glycidyl methacrylate) latex microsphere emulsion for reaction for 2 hours, thus obtaining colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere is obtained.
Comparative example 3
The preparation method of the color latex microsphere comprises the following preparation steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 1g of acrylic acid and 3g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, dividing into trisections, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours at 80 ℃, then heating to 100 ℃, adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours, heating to 120 ℃, and adding the trisections into poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 2 hours to obtain colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere is obtained.
Comparative example 4
The preparation method of the color latex microsphere comprises the following preparation steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 3g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Dissolving 300mg of water-soluble dye tetramethylrhodamine isothiocyanate in 100mL of deionized water, adding the mixture into the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion at 120 ℃ at one time, and reacting for 6 hours to obtain colored polystyrene latex microsphere emulsion A after primary dyeing;
(3) Adding 12g of ethylenediamine into the color polystyrene latex microsphere emulsion A to react for 24 hours at 80 ℃ to obtain surface amino color polystyrene latex microsphere emulsion B;
(4) 300mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface-aminated color polystyrene latex microsphere emulsion B to react for 15h at 80 ℃, and the mixture is washed by the deionized water after the reaction is finished, so that the orange-red latex microsphere with nano-scale and uniform particle size is obtained.
Comparative example 5
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 3g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) 600mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water and divided into trisections, poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion is added at 80 ℃ for reaction for 2 hours, then the temperature is raised to 100 ℃ for reaction for 2 hours, poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion is added, then the temperature is raised to 120 ℃ for reaction for 2 hours, and finally the dyed orange-red polystyrene latex microsphere emulsion is obtained.
Comparative example 6
The preparation process of nanometer level color latex microsphere with homogeneous size includes the following steps:
(1) Introducing nitrogen into a three-neck flask filled with 200mL of deionized water, adding 0.2g of initiator potassium persulfate, uniformly stirring, then dropwise adding a mixed solution containing 20g of styrene, 3g of acrylic acid and 1g of glycidyl methacrylate, heating to 90 ℃ after the dropwise adding is finished, keeping the reaction for 5 hours, and cooling to room temperature to obtain white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion;
(2) Adding 12g of ethylenediamine into the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 24 hours at 80 ℃ to obtain the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion with an aminated surface;
(3) 600mg of water-soluble dye tetramethylrhodamine isothiocyanate is dissolved in 100mL of deionized water, and is added into the surface aminated poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion to react for 15h at 80 ℃, and after the reaction is finished, the deionized water is used for washing, so that the orange-red latex microsphere with nano-scale and uniform particle size is obtained.
Performance test:
particle size and particle size uniformity: testing with DB-525 Zeta PALS, loading a certain amount of color latex microspheres into a centrifuge tube, ultrasonically oscillating to disperse the microspheres in methanol, and testing the particle size on DB-525 Zeta PALS at room temperature;
dye-uptake rate: testing with UV-Vis;
The test results are shown in Table 1 below:
TABLE 1
Test items/instances Particle size (nm) Particle size uniformity (CV value/%) Dye uptake (%)
Example 1 232 3 95
Example 2 241 3 92
Example 3 238 4 93
Example 4 248 5 90
Comparative example 1 356 8 82
Comparative example 2 337 10 85
Comparative example 3 315 11 86
Comparative example 4 325 13 75
Comparative example 5 387 12 70
Comparative example 6 408 15 76
As can be seen from comparison of examples 1-4 and comparative examples 1-6 in Table 1, the invention obtains the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere by adding acrylic acid and glycidyl methacrylate in a specific ratio into the polystyrene latex microsphere, meanwhile, the dye is coated inside the polymer microsphere as much as possible in a sectional heating mode by adopting a secondary dyeing mode, and the functional group of the dye reacts with the amino group on the surface of the microsphere to achieve good covalent bonding by the secondary dyeing, so that the finally obtained colored latex microsphere has smaller particle size (< 250 nm), better particle size uniformity (CV value < 5%) and good dye uptake (> 90%).
As can be seen from comparison of examples 1 to 4 with comparative examples 1 to 3 in Table 1, when no acrylic acid or glycidyl methacrylate was added to the polystyrene latex microspheres, or the ratio of the two is not in conformity with the definition of the present invention, the particle size of the finally obtained colored latex microspheres was relatively large, the uniformity of the particle size was poor, and the dye uptake was poor, and it was found that the acrylic acid and glycidyl methacrylate in the polystyrene latex microspheres acted synergistically, probably because the water-soluble properties of acrylic acid and glycidyl methacrylate were different, the process rate of precipitating the microspheres during polymerization was different, and the particle size adjustment effect was different.
As can be seen from comparing examples 1-4 with comparative example 4, the properties obtained without the step-wise heating during the first dyeing process are poor, especially the dye uptake, probably because the step-wise heating brings about more uniformity of dye uptake.
The comparative examples 1 to 4 and comparative examples 5 to 6 show that the performance of the dye is inferior to that of the dye of the invention due to the fact that the dye is coated inside the microsphere as much as possible by twice dyeing, and the excessive dye is modified with the amino groups on the surface of the microsphere to obtain strong chemical bonding, so that the better dye uptake is ensured.
Finally, it should be noted that the foregoing embodiments are merely for illustrating the technical solution of the embodiments of the present invention and are not intended to limit the embodiments of the present invention, and although the embodiments of the present invention have been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the embodiments of the present invention may be modified or replaced with the same, and the modified or replaced technical solution may not deviate from the scope of the technical solution of the embodiments of the present invention.

Claims (9)

1. The preparation method of the nano-scale uniform-particle-size color latex microsphere is characterized by comprising the following preparation steps:
s1, preparing polystyrene latex microsphere emulsion by soap-free emulsion polymerization;
S2, dissolving a certain amount of water-soluble dye in a certain amount of deionized water, adding the water-soluble dye into the polystyrene latex microsphere emulsion in batches and time by a sectional heating method, and stirring and reacting for a certain time to obtain a colored polystyrene latex microsphere emulsion A after primary dyeing;
s3, adding ethylenediamine into the color polystyrene latex microsphere emulsion A, and heating and reacting for a certain time to obtain surface amino color polystyrene latex microsphere emulsion B;
s4, dissolving a certain amount of water-soluble dye in a certain amount of deionized water, adding the deionized water into the surface-aminated color polystyrene latex microsphere emulsion B, heating and reacting for a certain time at a certain temperature, and washing with the deionized water after the reaction is finished to obtain the nanoscale color latex microsphere with uniform particle size;
The polystyrene latex microsphere emulsion in the step S1 is poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion; the mass ratio of the mass of the styrene to the mass of the acrylic acid and the glycidyl methacrylate in the preparation process of the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion is (5-15): 1, a step of; the mass ratio of the acrylic acid to the glycidyl methacrylate is (1-3): 1, a step of;
The water-soluble dye in the step S2 is selected from fluorescein isothiocyanate or tetramethyl rhodamine isothiocyanate;
The sectional heating method comprises the following steps: adding the mixture into the polystyrene latex microsphere emulsion at 80 ℃ for reaction for 2 hours, heating to 100 ℃ for reaction for 2 hours, and heating to 120 ℃ for reaction for 2 hours.
2. The method for preparing colored latex microspheres according to claim 1, wherein the poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion of step S1 is prepared by the following steps:
Introducing nitrogen into a three-neck flask containing a certain amount of deionized water, adding a certain amount of initiator, stirring uniformly, then dropwise adding a mixed solution of styrene, acrylic acid and glycidyl methacrylate, heating to 70-90 ℃ after the dropwise adding is finished, keeping the reaction for 2-5h, and cooling to room temperature to obtain the white poly (styrene-acrylic acid-glycidyl methacrylate) latex microsphere emulsion with carboxyl and epoxy groups modified on the surface.
3. The method of preparing colored latex microspheres according to claim 2, wherein the initiator is selected from potassium persulfate or ammonium persulfate;
the mass ratio of the styrene, the acrylic acid and the glycidyl methacrylate to the initiator is 100: (0.5-2);
the mass ratio of the styrene to the water-soluble dye is 10: (0.1-3).
4. The method for preparing color latex microspheres according to claim 1, wherein the mass ratio of the water-soluble dye to deionized water is (3-6): 1, a step of; the sectional heating method is added in batches and time-by-time specifically comprises the following steps: the water-soluble dye dissolved in deionized water is divided into three parts, and then added into polystyrene latex microsphere emulsion at 80 ℃ to react for 2 hours, then heated to 100 ℃ to react for 2 hours, and then heated to 120 ℃ to react for 2 hours.
5. The method for preparing color latex microspheres according to claim 1, wherein the amount of ethylenediamine added in the step S3 is 2 to 3 times the mass of both acrylic acid and glycidyl methacrylate; the heating reaction temperature is 80 ℃ and the reaction time is 12-24 hours.
6. The method for preparing color latex microspheres according to claim 1, wherein the mass ratio of the water-soluble dye to deionized water in step S4 is (3-6): 1, the heating temperature is 60-80 ℃ and the reaction time is 12-15h.
7. A nano-sized, uniform particle size colored latex microsphere prepared by the method of preparing a colored latex microsphere according to any one of claims 1 to 6.
8. The colored latex microsphere of claim 7, wherein the colored latex microsphere has a particle size of < 250nm, a particle size uniformity CV value of < 5%, and a dye uptake of greater than or equal to 90%.
9. Use of the nano-sized, uniform particle size colored latex microspheres prepared by the method for preparing colored latex microspheres according to any one of claims 1-6 or the colored latex microspheres according to any one of claims 7-8 as markers in immunochromatography.
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CN115975116A (en) * 2023-02-15 2023-04-18 杭州旭科生物技术有限公司 A preparation method of colored latex microspheres, colored latex microspheres and uses thereof

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CN113667048A (en) * 2021-08-16 2021-11-19 安徽为臻生物工程技术有限公司 Monodisperse polymer color microsphere and preparation method and application thereof
CN115975116A (en) * 2023-02-15 2023-04-18 杭州旭科生物技术有限公司 A preparation method of colored latex microspheres, colored latex microspheres and uses thereof

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