CN117046405A - Preparation method of agarose-based gel microspheres - Google Patents
Preparation method of agarose-based gel microspheres Download PDFInfo
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- CN117046405A CN117046405A CN202311000004.5A CN202311000004A CN117046405A CN 117046405 A CN117046405 A CN 117046405A CN 202311000004 A CN202311000004 A CN 202311000004A CN 117046405 A CN117046405 A CN 117046405A
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- 229920000936 Agarose Polymers 0.000 title claims abstract description 119
- 239000004005 microsphere Substances 0.000 title claims abstract description 115
- 238000002360 preparation method Methods 0.000 title claims description 15
- 238000000034 method Methods 0.000 claims abstract description 59
- 239000007788 liquid Substances 0.000 claims abstract description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000000725 suspension Substances 0.000 claims abstract description 34
- 238000005507 spraying Methods 0.000 claims abstract description 29
- 238000010438 heat treatment Methods 0.000 claims abstract description 16
- 238000000889 atomisation Methods 0.000 claims abstract description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 229920002873 Polyethylenimine Polymers 0.000 claims description 7
- 229920001661 Chitosan Polymers 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 229920002125 Sokalan® Polymers 0.000 claims description 5
- 239000004584 polyacrylic acid Substances 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 4
- 239000002105 nanoparticle Substances 0.000 claims description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- 239000003595 mist Substances 0.000 claims description 3
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 2
- 239000011543 agarose gel Substances 0.000 abstract description 67
- 239000000499 gel Substances 0.000 abstract description 24
- 239000002245 particle Substances 0.000 abstract description 21
- 238000004519 manufacturing process Methods 0.000 abstract description 16
- 230000008569 process Effects 0.000 abstract description 12
- 239000003960 organic solvent Substances 0.000 abstract description 10
- 239000012071 phase Substances 0.000 abstract description 10
- 238000005406 washing Methods 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 5
- 239000004094 surface-active agent Substances 0.000 abstract description 4
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 230000004048 modification Effects 0.000 abstract description 2
- 238000012986 modification Methods 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- 230000000052 comparative effect Effects 0.000 description 12
- 238000000635 electron micrograph Methods 0.000 description 12
- 238000007711 solidification Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000012528 membrane Substances 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000004945 emulsification Methods 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 239000002826 coolant Substances 0.000 description 5
- 239000000498 cooling water Substances 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004140 cleaning Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000003321 amplification Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000110 cooling liquid Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 206010067482 No adverse event Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000007793 non-solvation Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0052—Preparation of gels
- B01J13/0065—Preparation of gels containing an organic phase
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
- C08J3/122—Pulverisation by spraying
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/12—Agar-agar; Derivatives thereof
Abstract
The invention discloses a production method of agarose-based gel microspheres. The method comprises the following steps: firstly, agarose is dispersed in water to prepare agarose suspension; heating again to dissolve to form agarose solution; spraying the agarose solution into fog-like liquid drops through an atomization device; the atomized liquid drops are kept at a certain height above the diversion layer, settled in the air and naturally cooled to form agarose gel microspheres, and the agarose gel microspheres flow into the collecting device along with diversion liquid to prepare small liquid drops with the size of 5-200 mu m. The method has simple process, and oil phase, surfactant and organic solvent are not required to be used; separation and washing are not needed; the prepared microsphere has uniform particle size, good batch repeatability and easy realization of modification of functional groups and large-scale production.
Description
Technical Field
The invention relates to the technical field of agarose gel medium preparation, in particular to a preparation method of agarose gel microspheres.
Background
The agarose gel microsphere is prepared by an emulsification-solidification method, a spraying method, a microfluidic droplet method, a membrane emulsification method and the like.
Among these methods, the emulsion-solidification method is the most widely used method for preparing agarose gel microspheres, and the main principle is that an aqueous phase solution obtained by heating and dissolving agarose is dispersed in an oil phase containing a surfactant, stirred and emulsified to form a W/O type emulsion system, and cooled to a temperature far below the gel point to solidify liquid drops, thereby forming agarose microspheres. The traditional emulsification-solidification method has the characteristics of simple process, low equipment requirement, easy amplification and the like, but the emulsification-solidification method needs a large amount of oil phase (liquid paraffin, petroleum ether and the like) and surfactant in the emulsification process, and also needs a large amount of organic solvent in the demulsification process (normal hexane, xylene and the like) and the solid-liquid separation washing process (ethanol), and the separation and washing of the obtained agarose microspheres from the emulsion take a large amount of time. In addition, the agarose microsphere prepared by the emulsification-solidification method has the problems of wider particle size distribution, difficult control of microsphere diameter and the like.
The microfluidic drop method is a new method for preparing agarose gel microspheres, and can obtain agarose gel microspheres with uniform particle size smaller than 100 microns under mild conditions. The microfluidic device mainly comprises an inner pipe and an outer pipe, wherein the outer pipe is connected with a pneumatic pump and is provided with an oil phase containing a surface emulsifier; the inner tube is provided with agarose water solution, the inner tube and the outer tube flow out at the same flow speed under the gas pressure, so that the water phase and the oil phase are emulsified to form spherical liquid drops in the propelling process, and the spherical liquid drops are collected into buffer solution and cooled to obtain agarose gel microspheres. Compared with other methods, the microfluidic droplet method has the advantages of uniform particle size, low solvent consumption, no toxic effect on cells and the like, but has the problems of slow preparation process, difficult amplification and the like, so that the microfluidic droplet method is widely used for preparing microspheres on a laboratory scale.
The membrane emulsification method was originally proposed by Nakashima et al in 1988 for the first time to solve the problem of non-uniformity of emulsion in food products. Later, ma Guanghui institutions et al applied this technology to the preparation of various microspheres such as agarose, polypropylene, and polymethacrylate. The main principle of the method is that agarose water solution passes through a microporous membrane under a certain pressure to enable the tail end of the membrane hole to generate liquid drops, then the liquid drops are washed down by oil phase, and the agarose gel microsphere is obtained by cooling and solidifying. Compared with other methods, the membrane emulsification method has the advantages of the traditional emulsification method, and simultaneously has the unique advantages of uniform particle size, good batch repeatability and the like of the prepared microspheres. However, the method has high requirements on the membrane, and has certain mechanical strength, high pressure and high temperature resistance, uniform membrane pore diameter, proper porosity and other equipment conditions, so that the membrane emulsification method is difficult to be applied to scale-up in industrial production.
In order to solve the problem that the particle size of agarose gel microspheres prepared by an emulsification-solidification method is difficult to control, philipson and Bengtsson jointly propose a novel preparation method, namely a spray cooling method, in 1964, a spray device with a certain caliber is designed, and hot agarose solution is sprayed into an organic solvent with lower temperature by adopting high-pressure nitrogen, so that high-temperature liquid drops are quickly solidified into balls when meeting cold after entering the receiving solvent, and the purpose of preparing agarose gel microspheres with different particle sizes is achieved: for example, CN102233254a discloses that mist droplets are sprayed into an organic phase to solidify into spheres; CN102166504a discloses that droplets are atomized into tiny droplets and then enter into a gel solidification liquid to solidify. However, most of the adopted receiving solvents are volatile, inflammable and explosive organic reagents, which cause problems for production safety. In addition, a large amount of purified water is needed for cleaning after the microspheres are recovered, otherwise, the microspheres are easy to adhere, a large amount of wastewater is generated, and the production cost is increased. CN115477766a discloses that the precursor solution drops into liquid nitrogen in the form of droplets to form ice balls, after the liquid nitrogen is completely volatilized, a cross-linking agent is added to crosslink the ice balls to form hydrogel microspheres. CN111097344a discloses that tiny spherical droplets are formed on a conveyor belt, and then rapidly frozen into tiny ice balls through a channel of a quick-freezing box.
Disclosure of Invention
The invention provides an innovative invention aiming at the problems of large oil phase and organic solvent consumption, more water consumption and long time consumption for separation and washing, slow preparation process, difficult amplification and the like in the existing four microsphere preparation processes, and realizes the green preparation of agarose-based gel microspheres without oil phase, organic solvent, cleaning and separation. The invention aims to provide a device.
In order to achieve the above purpose, the invention provides an agarose-based gel microsphere and a preparation method thereof, which are characterized by comprising the following steps:
s1, dispersing agarose monomer or agarose and functional substance complex in water to prepare agarose monomer or complex suspension;
s2, dissolving the obtained suspension by heating to form a uniform solution;
s3, spraying the obtained uniform solution into fog-like liquid drops through an atomization device;
s4, the vaporific liquid drops are kept at a certain height above the diversion layer, are settled in the air and naturally cooled to form agarose-based gel microspheres, and the agarose-based gel microspheres flow into the collecting device along with diversion liquid.
Further, the functional substance is at least one selected from sodium chloride, ferroferric oxide nano particles, polyethyleneimine, polyacrylic acid and chitosan;
optionally, the addition amount of the functional substance is 0.5-50wt%.
Further, in the step S1, the mass concentration of the suspension is 2% -12%.
Further, in the step S3, the spraying pressure is 0.05-0.2 Mpa;
in the step S4, the height of the mist droplets above the diversion layer, namely the height of the spray nozzle and the surface of the diversion layer is 140-200 cm, the air temperature is 0-35 ℃, and the diversion liquid temperature is 0-40 ℃.
Further, in the step S4, the diversion liquid is deionized water or an ethanol-water solution.
The invention also protects the agarose-based gel microsphere prepared by the preparation method.
Compared with the prior art, the invention has the following advantages:
(1) According to the process for preparing the agarose-based gel microspheres by using the spray method, provided by the invention, an emulsion system is not required to be prepared, namely, a surfactant, an oil phase and an organic solvent are not required to be added, so that the agarose-based gel microspheres can be obtained. The method effectively avoids the processes of demulsification by adding organic solvents such as n-hexane and the like, washing by adding solvents such as ethanol and the like in the process of preparing the microspheres by an emulsion curing method, and further realizes no solvation in the process of preparing the microspheres.
(2) The emulsion solidification method generally adopts organic solvents such as ethyl acetate and the like as solidification coolants. Ethyl acetate is a commonly used coolant, and its low viscosity and low density properties make it have a very high sedimentation rate, when the agarose solution is atomized and then enters into cooled ethyl acetate, the atomized droplets can be quickly solidified into microspheres when the temperature is quickly reduced to the freezing point of agarose due to the immiscibility of agarose. However, ethyl acetate is a flammable and volatile organic solvent, which affects the health of operators. In addition, ethyl acetate is slightly soluble in water, and agarose microspheres are easy to enrich ethyl acetate after being solidified in ethyl acetate, so that a large amount of pure water is required for cleaning. According to the invention, agarose gel microspheres are formed by utilizing the principle that agarose fog drops are naturally cooled and solidified in the air sedimentation process, and are guided into the collecting container along with pure water in the flow guide layer for collection, and the pure water in the collecting container can be recycled, so that the processes of adopting an organic solvent as a solidifying cooling agent and adopting a large amount of pure water to clean the microspheres are avoided, and further, the non-solvation of the microsphere cleaning process is realized.
(3) The microsphere prepared by the method has uniform particle size, good batch repeatability and easy realization of large-scale production.
(4) The preparation method of the agarose-based gel microsphere provided by the invention is not only suitable for preparing agarose gel microspheres, but also suitable for preparing agarose gel microspheres such as amino-functional and carboxyl-functional agarose gel microspheres, and is also suitable for preparing agarose magnetic microspheres.
Drawings
FIG. 1 is a schematic view of the apparatus and process flow of the present invention.
FIG. 2 is an electron micrograph of agarose gel microspheres prepared in comparative example 1.
FIG. 3 is an electron micrograph of agarose gel microspheres prepared in comparative example 2.
FIG. 4 is an electron micrograph of agarose gel microspheres prepared in comparative example 3.
FIG. 5 is an electron micrograph of agarose gel microspheres prepared in comparative example 4.
FIG. 6 is an electron micrograph of agarose gel microspheres prepared in example 1.
FIG. 7 is an electron micrograph of agarose gel microspheres prepared in example 2.
FIG. 8 is an electron micrograph of agarose gel microspheres prepared in example 3.
FIG. 9 is an electron micrograph of agarose gel microspheres prepared in example 4.
FIG. 10 is an electron micrograph of agarose gel microspheres prepared in example 5.
FIG. 11 is an electron micrograph of agarose gel microspheres prepared in example 6.
FIG. 12 is an electron micrograph of agarose gel microspheres prepared in example 7.
FIG. 13 is an electron micrograph of agarose gel microspheres prepared in example 8.
Detailed Description
Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative and intended to explain the present invention and should not be construed as limiting the invention. The specific techniques or conditions are not identified in the examples and are performed according to techniques or conditions described in the literature in this field or according to the product specifications. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Comparative example 1: production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 0.5wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.1MPa;
s5, the distance between the atomizing nozzle and the solidifying cooling liquid ethyl acetate is 15cm, and the atomized liquid drops are quickly solidified in the ethyl acetate to form agarose gel microspheres.
S6, filtering the agarose gel microspheres by a filter screen to obtain agarose gel microspheres, and purifying the agarose gel microspheres by pure water (m Agarose gel ：m Water and its preparation method =1: 10 After 5 times of washing, the residual ethyl acetate is removed, and finally 30-250 mu m agarose gel microspheres are obtained. The results are shown in FIG. 2. It can be seen that comparative example 1 uses ethyl acetate coolant, and the distance between the atomizing nozzle and the ethyl acetate coolant is too short, resulting in non-uniform particle size and irregular morphology of the microspheres.
Comparative example 2 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 0.5wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.05MPa;
s5, the distance between the atomizing nozzle and the solidified cooling water (0 ℃) is 15cm, and atomized liquid drops are solidified in the cooling water.
S6, filtering the coagulated sample by a filter screen to finally obtain agarose gel blocks, wherein the agarose gel blocks cannot form dispersed agarose gel microspheres. The results are shown in FIG. 3. It can be seen that this comparative example 2 uses cooling water, but the distance between the atomizing nozzle and the cooling water is too short, and it is also possible to form dispersed agarose gel microspheres.
Comparative example 3 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 0.5wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.05MPa;
s5, the distance between the atomizing nozzle and the solidified ethyl acetate cooling liquid (0 ℃) is 15cm, and atomized liquid drops are solidified in ethyl acetate.
S6, filtering the coagulated sample by a filter screen to finally obtain the agarose gel microspheres with the particle size of 50-160 mu m. The results are shown in FIG. 4. As can be seen, in comparative example 3, ethyl acetate cooling liquid was used, the distance between the atomizing nozzle and the cooling water was too short, and the particle size of the formed agarose gel microspheres was not uniform, and was 50-160. Mu.m.
Comparative example 4 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 1.0wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.05MPa;
s5, the distance between the atomizing nozzle and the surface of the deionized water diversion layer is 75cm, atomized liquid drops are settled in the air in the height and naturally cooled to form agarose gel microspheres, and the air temperature is 25 ℃.
S6, the agarose gel microspheres flow into a filter screen through a diversion layer to be collected, and finally 50 mu m agarose gel microspheres are obtained, wherein the sphericity of the microspheres is poor, and part of the microspheres are missing. The results are shown in FIG. 5. The deionized water diversion layer is used in the comparative example 4, but the cooling distance between the atomizing nozzle and the diversion layer is still too short, the sphericity of the microsphere is poor, and some microsphere is missing.
Example 1 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with mass concentration of 2%;
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 2.0wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.05MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 140cm, atomized liquid drops are settled in the air in the height and naturally cooled to form agarose gel microspheres, and the air temperature is 0 ℃.
S6, enabling the agarose gel microspheres to flow into a filter screen along with deionized guide liquid with the temperature of 0 ℃ in the guide layer to be collected, and finally obtaining the agarose gel microspheres with the particle size of about 30 mu m. The results are shown in FIG. 6.
Example 2 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4%;
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 0.5wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.2MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 140cm, atomized liquid drops are settled in the air in the height and naturally cooled to form agarose gel microspheres, and the air temperature is 35 ℃.
S6, enabling the agarose gel microspheres to flow into a filter screen along with deionized water flow guide liquid with the temperature of 25 ℃ in the flow guide layer to be collected, and finally obtaining the agarose gel microspheres with the particle size of about 5 mu m. The results are shown in FIG. 7.
Example 3 production method of agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 12% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, weighing 2.0wt% of sodium chloride into the agarose solution, and uniformly dispersing the added substances into the agarose solution by stirring.
S4, spraying the agarose solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.2MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 200cm, atomized liquid drops are settled in the air in the height and naturally cooled to form agarose gel microspheres, and the air temperature is 40 ℃.
S6, the agarose gel microspheres flow into a filter screen through 20% (v/v) ethanol-water diversion liquid with the temperature of 40 ℃ in the diversion layer for collection, and finally the agarose gel microspheres with the particle size of about 65 mu m are obtained. The results are shown in FIG. 8.
Example 4 production method of magnetic agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, adding Fe with the particle size of 25% (w/v) of 10nm into the agarose solution 3 O 4 And (5) stirring the nano particles uniformly.
S4, agarose-Fe 3 O 4 The mixed solution is sprayed into fog-like liquid drops through an atomization device, and the spraying pressure is highAdjusting to 0.15MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 160cm, atomized liquid drops are settled in the air in the height and naturally cooled to form the magnetic agarose gel microsphere, and the air temperature is 16 ℃.
S6, enabling the magnetic agarose gel microspheres to flow into a filter screen through deionized water diversion liquid with the temperature of 0 ℃ in the diversion layer for collection, and finally obtaining the magnetic agarose gel microspheres with the particle size of about 30 mu m. The results are shown in FIG. 9.
Example 5 production method of magnetic agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 8% (w/v);
s2, dissolving the agarose suspension by heating to form agarose solution;
s3, adding Fe with the particle size of 50% (w/v) of 10nm into the agarose solution 3 O 4 And (5) stirring the nano particles uniformly.
S4, agarose-Fe 3 O 4 Spraying the mixed solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.15MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 150cm, atomized liquid drops are settled in the air in the height and naturally cooled to form the magnetic agarose gel microsphere, and the air temperature is 0 ℃.
S6, the magnetic agarose gel microspheres flow into a filter screen through deionized guide liquid with the temperature of 0 ℃ in the guide layer to be collected, and finally the magnetic agarose gel microspheres with the particle size of about 200 mu m are obtained. The results are shown in FIG. 10.
Example 6 production method of amino-functionalized agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, adding polyethyleneimine with the mass concentration of 0.5% (w/v) into agarose suspension;
s3, dissolving the agarose-polyethyleneimine suspension by heating to form agarose-polyethyleneimine solution;
s4, spraying the agarose-polyethyleneimine mixed solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.1MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 160cm, atomized liquid drops are settled in the air in the height and naturally cooled to form amino functional agarose gel microspheres, and the air temperature is 25 ℃.
S6, the amino-functionalized agarose gel microspheres flow into a filter screen through deionized guide liquid with the temperature of 25 ℃ in a guide layer to be collected, and finally the amino-functionalized agarose gel microspheres with the particle size of about 50 μm are obtained. The results are shown in FIG. 11.
Example 7 production method of amino-functionalized agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 4% (w/v);
s2, adding chitosan with the mass concentration of 0.5% (w/v) into the agarose suspension;
s3, dissolving the agarose-chitosan suspension by heating to form agarose-chitosan solution;
s4, spraying the agarose-chitosan mixed solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.1MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 160cm, atomized liquid drops are settled in the air in the height and naturally cooled to form amino functional agarose gel microspheres, and the air temperature is 25 ℃.
S6, the amino-functionalized agarose gel microspheres flow into a filter screen through deionized guide liquid with the temperature of 25 ℃ in a guide layer to be collected, and finally the amino-functionalized agarose gel microspheres with the particle size of about 50 μm are obtained. The results are shown in FIG. 12.
Example 8 production method of carboxyl-functionalized agarose-based gel microspheres
The method comprises the following steps:
s1, dispersing agarose into water to prepare agarose suspension with the mass concentration of 6% (w/v);
s2, adding polyacrylic acid with the mass concentration of 0.5% (w/v) into the agarose suspension;
s3, dissolving the agarose-polyacrylic acid suspension by heating to form agarose-polyethyleneimine solution;
s4, spraying the agarose-polyacrylic acid mixed solution into fog-like liquid drops through an atomization device, and adjusting the spraying pressure to 0.1MPa;
s5, the distance between the atomizing nozzle and the surface of the diversion layer is 160cm, atomized liquid drops are settled in the air in the height and naturally cooled to form carboxyl functional agarose gel microspheres, and the air temperature is 10 ℃.
S6, enabling the carboxyl functional agarose gel microspheres to flow into a filter screen through deionized guide liquid with the temperature of 10 ℃ in a guide layer for collection, and finally obtaining the carboxyl functional agarose gel microspheres with the particle size of about 45 mu m. The results are shown in FIG. 13.
Although embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the invention, and that variations, modifications, alternatives, and variations may be made in the above embodiments by those skilled in the art without departing from the spirit and principles of the invention.
Claims (7)
1. An agarose-based gel microsphere and a preparation method thereof are characterized by comprising the following steps:
s1, dispersing agarose monomer or agarose and functional substance complex in water to prepare agarose monomer or complex suspension;
s2, dissolving the obtained suspension by heating to form a uniform solution;
s3, spraying the obtained uniform solution into fog-like liquid drops through an atomization device;
s4, the vaporific liquid drops are kept at a certain height above the diversion layer, are settled in the air and naturally cooled to form agarose-based gel microspheres, and the agarose-based gel microspheres flow into the collecting device along with diversion liquid.
2. The preparation method according to claim 1, wherein the functional substance is at least one selected from sodium chloride, ferroferric oxide nanoparticles, polyethylenimine, polyacrylic acid, and chitosan;
optionally, the addition amount of the functional substance is 0.5-50wt%.
3. The method according to claim 1, wherein the mass concentration of the suspension in the step S1 is 2% to 12%.
4. The method according to claim 1, wherein the spraying pressure in the step S3 is 0.05 to 0.2MPa.
5. The method according to claim 1, wherein in the step S4, the height of the mist droplets above the diversion layer, i.e. the height of the spray nozzle and the surface of the diversion layer, is 140-200 cm, the air temperature is 0-35 ℃, and the diversion liquid temperature is 0-40 ℃.
6. The method according to claim 1 or 2, wherein in step S4, the diversion liquid is deionized water or an ethanol-water solution.
7. An agarose-based gel microsphere prepared by the method of any one of claims 1-6.
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