Quaternary ammonium salt modified magnetic microspheres and preparation method thereof

Abstract

The invention discloses a quaternary ammonium salt modified magnetic microsphere and a preparation method thereof, and relates to the technical field of polymer microsphere preparation, and the preparation method comprises the following steps: modifying an epoxy group of a silicon hydroxyl magnetic microsphere through an epoxy group silane coupling agent, extending a spacer arm through a diamine compound, and coating the surface of the microsphere with a quaternary ammonium salt group. In the invention, the surface of the magnetic microsphere is coated with a large number of quaternary ammonium salt groups, the ligands have good physical and chemical stability, and quaternary ammonium salt spacer arms on the surface of the microsphere are adjusted by selecting diamine compounds with different carbon chain lengths, so that quaternary ammonium salt magnetic microspheres with different spacer arms can be obtained.

Description

Technical Field

[0001] The invention relates to the technical field of polymer microsphere preparation, in particular to a quaternary ammonium salt-modified magnetic microsphere and a preparation method thereof. Background Art

[0002] Magnetic microspheres are a multi-purpose composite material, usually coated with biocompatible materials such as cellulose, chitosan, silica and polystyrene. Through the active groups on the surface (hydroxyl, epoxy, amino, carboxyl, thiol, quaternary ammonium salt, etc.), fluorescent molecules, antibodies and nucleic acids are loaded, which can specifically identify cancer cells, viruses and genetic materials. With its excellent magnetic response characteristics, magnetic microspheres can achieve rapid separation and enrichment, and have broad application prospects in the fields of immunoassay, cell separation and environmental testing. Currently, there are magnetic microspheres modified by quaternary ammonium salts. For example, CN111116851A discloses a method for preparing a core-shell structured polymeric quaternary ammonium salt magnetic microsphere, which specifically discloses dispersing seed microspheres in an organic solvent, adding a silane coupling agent under mechanical stirring conditions, and adjusting the pH value to make the solution alkaline to obtain double-bond modified magnetic microspheres, and then dispersing the double-bond modified magnetic microspheres in an organic solvent, adding a quaternary ammonium salt monomer, an initiator, and a cross-linking agent, and under corresponding reaction conditions, obtaining quaternary ammonium salt modified magnetic microspheres. In addition, CN117844801 A discloses a pathogenic bacteria enrichment and pretreatment kit, which specifically discloses quaternary ammonium salt modified polystyrene magnetic beads, the core of which is Fe3O4, and has a strong anion exchange function. Among the above-mentioned disclosed technologies, the preparation method of a core-shell structured polyquaternary ammonium salt magnetic microsphere disclosed in CN 111116851 A, the quaternized magnetic microspheres prepared therefrom are non-monodispersed, and the dispersion effect needs to be further improved, and the enrichment and pretreatment kit for pathogenic bacteria disclosed in CN 117844801 A, wherein the spacer arm of the quaternary ammonium salt modified by the magnetic beads is short, the chemical structure has only 3 carbon atoms, and the steric hindrance is large, which is not conducive to the binding of biomacromolecules. This paper extends the spacer arm of the quaternary ammonium salt magnetic microspheres by diamine compounds, reduces the steric hindrance effect, and proposes a preparation method of quaternary ammonium salt modified magnetic microspheres. Summary of the invention

[0003] The purpose of the present invention is to provide a quaternary ammonium salt modified magnetic microsphere and a preparation method thereof, so as to solve the above technical problems.

[0004] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0005] A quaternary ammonium salt-modified magnetic microsphere, the structural formula of the group modified on the surface of the microsphere is as follows:

[0006]

[0007] A method for preparing magnetic microspheres modified by quaternary ammonium salt comprises the following steps: dispersing the magnetic microspheres in an organic solvent, adding a silane coupling agent, a diamine compound and a quaternary ammonium salt under stirring, heating in a water bath to 50-90° C., reacting for 4-24 hours, and obtaining the magnetic microspheres modified by the quaternary ammonium salt.

[0008] Preferably, the magnetic microspheres are silanol microspheres with a particle size of 20 nm-5.0 μm.

[0009] Preferably, the silane coupling agent is a mixture of one or more of 3-glycidyloxypropyltrimethoxysilane, 3-glycidyloxypropyltriethoxysilane, 3-glycidyloxypropylmethyldimethoxysilane and 3-glycidyloxypropylmethyldiethoxysilane.

[0010] Preferably, the organic solvent is ethanol, isopropanol, ethylene glycol, DMF, DMAC, DMSO, toluene.

[0011] Preferably, the diamine compound is a mixture of one or more of ethylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,5-pentanediamine, 1,6-hexanediamine, 1,7-heptanediamine, 1,8-octanediamine, 1,9-nonanediamine, 1,10-decanediamine, 1,11-undecanediamine, 1,12-dodecanediamine, 1,14-tetradecanediamine, 1,16-hexadecanediamine, 1,17-heptadecanediamine, and 1,18-octadecanediamine.

[0012] Preferably, the quaternary ammonium salt is glycidyl trimethyl ammonium chloride, glycidyl ethyl dimethyl ammonium chloride, glycidyl triethyl ammonium chloride, glycidyl ethyl dihydroxyethyl ammonium chloride.

[0013] Preferably, the molar ratio of the diamine compound to the quaternary ammonium salt is 1:1-1:5.

[0014] The beneficial effects of the present invention are:

[0015] 1. In the present invention, the surface of the magnetic microspheres is coated with a large number of quaternary ammonium salt groups, and the ligand has good physical and chemical stability. By selecting diamine compounds with different carbon chain lengths to adjust the quaternary ammonium salt spacer arms on the microsphere surface, quaternary ammonium salt magnetic microspheres with different spacer arms can be obtained.

[0016] 2. In the present invention, the content of quaternary ammonium salt groups on the surface of the magnetic microspheres can be adjusted by the feeding ratio of the silane coupling agent, the diamine compound and the quaternary ammonium salt. The experiment is simple, the operation is convenient, and it is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The SEM image of the magnetic microspheres modified with quaternary ammonium salt;

[0018] Figure 2 Zeta potential diagram of magnetic microspheres modified with quaternary ammonium salt;

[0019] Figure 3 The conductivity titration curve of the surface group content of magnetic microspheres modified with quaternary ammonium salt; DETAILED DESCRIPTION

[0020] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0022] The specific embodiments of the present invention are described below with reference to the accompanying drawings.

[0023] Example 1

[0024] In this embodiment, a method for preparing magnetic microspheres modified with quaternary ammonium salt is proposed, and the process is as follows:

[0025] Weigh 1.0 g of silanol magnetic microspheres, add them into a 250 mL three-necked flask, add 100 mL of DMF solution, add 0.20 mL of 3-glycidyloxypropyltrimethoxysilane while stirring, react in a 50°C water bath for 18 hours, magnetically separate, remove the supernatant, wash the precipitate with ethanol four times to obtain magnetic microspheres modified with surface epoxy groups, disperse them with ethanol, and store them for later use.

[0026] Example 2

[0027] In this embodiment, a method for preparing magnetic microspheres modified with quaternary ammonium salts is proposed, and the process is as follows: 1.0 g of silanol magnetic microspheres are weighed and added to a 250 mL three-necked flask, 100 mL of DMF solution is added, 0.50 mL of 3-glycidyloxypropyltrimethoxysilane is added under stirring, and the mixture is reacted for 18 hours in a 50° C. water bath, magnetic separation is performed, the supernatant is removed, and the precipitate is washed 4 times with ethanol to obtain magnetic microspheres modified with epoxy groups on the surface, which are dispersed with ethanol and stored for later use.

[0028] Example 3

[0029] In this embodiment, a method for preparing magnetic microspheres modified with quaternary ammonium salts is proposed, and the process is as follows: 1.0 g of epoxy-modified magnetic microspheres are weighed and added to a 250 mL three-necked flask, 100 ml of ethanol is added, 0.20 ml of ethylenediamine is added under stirring, a 50° C. water bath is added, and the reaction is carried out for 2 hours, and then 1.13 g of trimethyl ammonium chloride is added, a 50° C. water bath is added, and the reaction is carried out for 4 hours, magnetic separation is performed, the supernatant is removed, and the precipitate is washed 4 times with ultrapure water to obtain magnetic microspheres with surface modified with quaternary ammonium salts, which are stored for later use.

[0030] Example 4

[0031] In this embodiment, a method for preparing magnetic microspheres modified with quaternary ammonium salt is proposed, and the process is as follows:

[0032] Weigh 1.0 g of epoxy-modified magnetic microspheres, add them into a 250 mL three-necked flask, add 100 ml of ethanol, add 0.40 ml of ethylenediamine while stirring, and react for 2 hours in a 50°C water bath. Then add 2.26 g of glycidyl trimethylammonium chloride, and react for 4 hours in a 50°C water bath. Perform magnetic separation, remove the supernatant, and wash the precipitate with ultrapure water 4 times to obtain magnetic microspheres modified with quaternary ammonium salts on the surface, which are stored for later use.

[0033] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0034] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A quaternary ammonium salt-modified magnetic microsphere, characterized in that: The structural formula of the group modified on the surface of the microsphere is as follows:

2. The method for preparing the quaternary ammonium salt-modified magnetic microspheres according to claim 1, characterized in that: The magnetic microspheres are dispersed in an organic solvent, and a silane coupling agent, a diamine compound and a quaternary ammonium salt are added under stirring, and the mixture is heated to 50-90° C. in a water bath and reacted for 4-24 hours to obtain magnetic microspheres modified with the quaternary ammonium salt.

3. The preparation method according to claim 2, characterized in that: The magnetic microspheres are silicon hydroxyl microspheres with a particle size of 20nm-5.0μm.

4. The preparation method according to claim 1, characterized in that: The silane coupling agent is a mixture of one or more of 3-glycidyloxypropyltrimethoxysilane, 3-glycidyloxypropyltriethoxysilane, 3-glycidyloxypropylmethyldimethoxysilane and 3-glycidyloxypropylmethyldiethoxysilane.

5. The preparation method according to claim 1, characterized in that: The organic solvents are ethanol, isopropanol, ethylene glycol, DMF, DMAC, DMSO, and toluene.

6. The preparation method according to claim 1, characterized in that: The diamine compound is a mixture of one or more of ethylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,5-pentanediamine, 1,6-hexanediamine, 1,7-heptanediamine, 1,8-octanediamine, 1,9-nonanediamine, 1,10-decanediamine, 1,11-undecanediamine, 1,12-dodecanediamine, 1,14-tetradecanediamine, 1,16-hexadecanediamine, 1,17-heptadecanediamine, and 1,18-octadecanediamine.

7. The preparation method according to claim 1, characterized in that: The quaternary ammonium salts are glycidyl trimethyl ammonium chloride, glycidyl ethyl dimethyl ammonium chloride, glycidyl triethyl ammonium chloride, and glycidyl ethyl dihydroxyethyl ammonium chloride.

8. The preparation method according to claim 1, characterized in that: The molar ratio of the diamine compound to the quaternary ammonium salt is 1:1-1:5.

Images