CN111085148B - Preparation method of chitosan microspheres with high specific surface area - Google Patents
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Abstract
The invention discloses a preparation method of chitosan microspheres with high specific surface area, and relates to the field of material preparation. The method comprises the steps of selecting a continuous phase, a disperse phase, a phase collecting system, selecting a micro-fluidic chip, modifying the chip, preparing microspheres and the like. The chitosan microspheres with high specific surface area, uniform size, controllable appearance, good biocompatibility and biodegradability are prepared by means of a micro-fluidic chip platform based on a 'flow focusing' principle and by combining an alcohol dehydration principle. The method for preparing the microstructure by the alcohol dehydration principle is simple, and the operation is convenient, so that the method is hopeful to become one of means for quickly preparing the material with the microstructure.
Description
Technical Field
The invention relates to the field of material preparation, in particular to a preparation method of chitosan microspheres with high specific surface area.
Background
Chitosan is also called chitosan and is obtained by deacetylation of chitin widely existing in nature, and has a chemical name of polyglucosamine (1-4) -2-amino-B-D glucose. Such natural polymers are receiving wide attention from various industries because of their excellent biofunctionality and compatibility, blood compatibility, safety, and microbial biodegradability. The application of chitosan as a biofunctional material such as drug release carrier, tissue engineering scaffold material, etc. is a hot spot of recent chitosan research. The chitosan can be used for preparing biological materials in various forms such as solution, gel, film, silk, microsphere and the like, the surface of the chitosan is positively charged, so that the attachment of cells is facilitated, and the excellent property of autofluorescence provides simplified possibility for the labeling and tracking of the chitosan. In addition, other materials can be used for functionally modifying the chitosan, so that the application range of the chitosan is expanded.
The microfluidic chip droplet technology is a brand new technology developed on a microfluidic chip for manipulating micro-volume liquid. Because the microfluidic droplet technology has the advantages of small volume, no sample diffusion, stable reaction conditions, less cross contamination among samples, rapid mixing and the like, the microfluidic droplet technology has been applied to a plurality of fields of physics, chemistry, biology such as cell research, material preparation, chemical reaction and the like. The formation of the liquid drops mainly comprises two modes of T-shaped channels and flow focusing. With the continuous improvement of the flux of the microfluidic droplet technology and the continuous development of the sample introduction, droplet fusion, splitting, sorting, capturing, storage and detection technologies, the droplet microfluidic technology will be more and more widely applied. The droplet microfluidic technology is expected to become a new platform for partial research in the chemical and biological fields. In addition, the preparation of materials such as microspheres and microcolumns by using a microfluidic chip platform is a hot point of research in recent years.
Disclosure of Invention
The invention aims to provide a preparation method of chitosan microspheres with high specific surface area.
The technical solution of the invention is as follows: a preparation method of chitosan microspheres with high specific surface area comprises the following steps:
(1) selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consists of oleic acid containing 1% to 5% by volume of span-80; the dispersed phase is formed by dissolving 1 to 5 mass percent of chitosan and 1 to 2 volume percent of acetic acid in deionized water; the collecting phase is composed of 4-8% of glutaraldehyde, 5-20% of alcohol and 1-5% of tween-20 by volume dissolved in deionized water
(2) Selecting a micro-fluidic chip: the chip comprises a dispersed phase inlet, a continuous phase inlet, a dispersed phase liquid channel, a continuous phase liquid channel and an outlet; the disperse phase liquid enters the disperse phase straight channel through the disperse phase inlet, the continuous phase liquid enters the continuous phase liquid channel through the continuous phase inlet, the channel is divided into two symmetrical flow paths towards two sides at the position close to the inlet, and the two continuous phase flow paths are respectively intersected with the disperse phase channel from the left side and the right side at the interface of the outlet channel and the disperse phase channel.
(3) Chip channel modification: placing the chip in a vacuum drier for vacuumizing for at least 10min, immediately adding FC40 solution containing 1H,1H,2H, 2H-perfluorooctyl trichlorosilane in a volume ratio of 2-4 into the chip, placing the chip at room temperature for 10-30 min, draining the liquid, placing the chip in an oven at 80 ℃ for at least 2H, and taking out the chip; then fixing the chip in a large-size plastic dish through PDMS glue for later use;
(4) preparing microspheres: pouring the collection phase into a large-size plastic dish until the collection phase submerges the outlet channel, and controlling the continuous phase by using an injection pump to fill the whole chip; and controlling the dispersed phase by an injection pump, wherein the flow rate ratio of the continuous phase to the dispersed phase is 2-20:1, and the size of the obtained chitosan microspheres is gradually reduced along with the increase of the flow rate ratio of the dispersed phase of the continuous phase, and the size range is 250-50 μm. .
The chip size is 6cm multiplied by 3cm, the channel height is 100-400 μm, the channel widths of the continuous phase and the disperse phase are 1/3 of the channel height, and the width of the outlet channel is consistent with the channel height.
According to the invention, alcohol is added into the collection phase, different surface microstructures can be obtained by controlling the alcohol concentration and the dehydration time, and the specific surface area of the chitosan microspheres is increased; the addition of the alcohol can ensure that the continuous phase enters the collecting phase and is dissolved in the collecting phase, thereby accelerating the crosslinking and curing speed of the dispersed phase and ensuring that the crosslinking and curing are more uniform. Making it promising as one of the means for rapidly preparing materials with microstructures.
Drawings
FIG. 1 is a schematic structural diagram of a microfluidic chip for preparing chitosan microspheres;
FIG. 2 is a graph of the results of droplet formation for mobile and dispersed phases in different proportions;
FIG. 3 is a schematic diagram of glutaraldehyde cross-linked chitosan principles;
FIG. 4 is a dimensional representation of a prepared microstructured chitosan microsphere;
FIG. 5 is a topographical representation of the prepared microstructured chitosan microspheres;
FIG. 6 is a graphical representation of the morphology of chitosan microspheres when the collected phase alcohol concentration is 0% by volume;
FIG. 7 is a graphical representation of the morphology of chitosan microspheres when the collected phase alcohol concentration is 5% by volume;
FIG. 8 is a graph of the morphology of chitosan microspheres when the collected phase alcohol concentration was 20% by volume.
Wherein: 1. continuous phase inlet 2, continuous phase channel 3, dispersed phase inlet 4, dispersed phase channel 5 and outlet
Detailed Description
The invention is further illustrated with reference to the following figures and examples.
Example 1
Preparation of chitosan microsphere with high specific surface area
(1) Selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consisted of oleic acid containing 2% span-80 by volume; the dispersed phase is formed by dissolving 2% of chitosan and 1% of acetic acid in deionized water by mass ratio; the collected phase is composed of 4% of glutaraldehyde, 10% of alcohol and 2% of tween-20 by volume dissolved in deionized water, chitosan can be crosslinked and cured under the action of glutaraldehyde, the principle of the chitosan is shown in figure 3, and the amino group of chitosan reacts with the aldehyde group of glutaraldehyde to realize crosslinking.
(2) Selecting a micro-fluidic chip: the chip comprises a dispersed phase inlet, a continuous phase inlet, a dispersed phase liquid channel, a continuous phase liquid channel and an outlet; the dispersed phase liquid enters a dispersed phase straight channel through a dispersed phase inlet, the continuous phase liquid enters a continuous phase liquid channel through a continuous phase inlet, the channel is divided into two symmetrical flow paths towards two sides at the position close to the inlet, the two continuous phase flow paths are respectively intersected with the dispersed phase channel from the left side and the right side at the interface of an outlet channel and the dispersed phase channel, and the chip structure is shown in figure 1.
(3) Chip channel modification: placing the chip in a vacuum drier, vacuumizing for 10min, immediately adding FC40 solution containing 2.5% by volume of 1H,1H,2H, 2H-perfluorooctyl trichlorosilane into the chip, placing the chip at room temperature for 20min, draining the liquid, placing the chip in an oven at 80 ℃ for 2H, and taking out the chip; and then fixing the chip in a large-size plastic dish through PDMS glue for later use.
(4) Preparing microspheres: pouring the collection phase into a large-size plastic dish until the collection phase submerges the outlet channel, and controlling the continuous phase by using an injection pump to fill the whole chip; controlling the dispersed phase by an injection pump, controlling the size of the obtained microspheres by regulating the flow rate of the continuous phase and the dispersed phase, wherein the flow rate ratio of the continuous phase to the dispersed phase is 2:1-20:1, the size of the obtained chitosan microspheres is gradually reduced along with the increase of the flow rate ratio of the dispersed phase of the continuous phase, and the size range is 250-50 μm; the process change is shown in FIG. 2; FIGS. 4 and 5 are graphs showing the results of microspheres obtained when the flow rate of the continuous phase and the flow rate of the dispersed phase are controlled to be 4:1, wherein the flow rate of the continuous phase is 4uL/min, and the flow rate of the dispersed phase is 1 uL/min.
The chip size is 6cm multiplied by 3cm, the channel height is 250 μm, the channel width of the continuous phase and the disperse phase is 100 μm, and the outlet channel width is 250 μm.
Example 2
Preparation of chitosan microspheres with different specific surface areas
(1) Selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consisted of oleic acid containing 2% span-80 by volume; the dispersed phase is formed by dissolving 2% of chitosan and 1% of acetic acid in deionized water by mass ratio; the chitosan is prepared by dissolving alcohol containing 0% of volume ratio, glutaraldehyde containing 4% of volume ratio and tween-20 containing 2% of volume ratio in deionized water, and can be crosslinked and cured under the action of glutaraldehyde, the principle of which is shown in figure 3, and the amino group of the chitosan reacts with the aldehyde group of the glutaraldehyde to realize crosslinking.
(2) Selecting a micro-fluidic chip: microfluidic chip same as in example 1
(3) Chip channel modification: chip modification method same as in example 1
(4) Preparing microspheres: controlling the flow rate ratio of the continuous phase to the dispersed phase to be 8:1, wherein the flow rate of the continuous phase is 4 mu L/min, and the flow rate of the dispersed phase is 0.5 mu L/min; the resulting microsphere structure is shown in FIG. 6, and from the results, it can be seen that when no alcohol was present in the collected phase, the resulting microspheres were smooth in surface and free of microstructure.
Example 3
Preparation of chitosan microspheres with different specific surface areas
1) Selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consisted of oleic acid containing 5% span-80 by volume; the dispersed phase is formed by dissolving 1% of chitosan and 2% of acetic acid in deionized water by mass ratio; the collected phase is composed of 6% of glutaraldehyde, 5% of alcohol and 1% of tween-20 by volume dissolved in deionized water, chitosan can be crosslinked and cured under the action of glutaraldehyde, the principle of which is shown in figure 3, and the amino group of chitosan reacts with the aldehyde group of glutaraldehyde to realize crosslinking.
(2) Selecting a micro-fluidic chip: microfluidic chip same as in example 1
(3) Chip channel modification: chip modification method same as in example 1
(4) Preparing microspheres: the ratio of the flow rates of the continuous phase and the dispersed phase is controlled to be 8:1, wherein the flow rate of the continuous phase is 4 muL/min, the flow rate of the dispersed phase is 0.5 muL/min, the structure of the obtained microsphere is shown in figure 7, and the specific surface area of the obtained chitosan microsphere is increased along with the increase of the concentration of the collected phase alcohol.
Example 4
Preparation of chitosan microspheres with different specific surface areas
(1) Selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consisted of oleic acid containing 1% span-80 by volume; the dispersed phase is formed by dissolving 1 percent of chitosan by mass and 1.5 percent of acetic acid by volume in deionized water; the collecting phase is composed of glutaraldehyde 8% by volume, alcohol 20% by volume and tween-20 1% by volume dissolved in deionized water, chitosan can be cross-linked and cured under the action of glutaraldehyde, the principle of which is shown in fig. 3, and the amino group of chitosan reacts with the aldehyde group of glutaraldehyde to realize cross-linking.
(2) Selecting a micro-fluidic chip: microfluidic chip same as in example 1
(3) Chip channel modification: chip modification method same as in example 1
(4) Preparing microspheres: controlling the flow rate ratio of the continuous phase to the dispersed phase to be 8:1, wherein the flow rate of the continuous phase is 4 mu L/min, and the flow rate of the dispersed phase is 0.5 mu L/min; the morphology of the obtained microspheres is shown in fig. 8, and it can be seen from the results that chitosan microspheres with different specific surface areas can be obtained by controlling the alcohol concentration in the collection phase.
The preparation method of the chitosan microsphere with high specific surface area can prepare the chitosan microsphere with high specific surface area, uniform size, controllable appearance, good biocompatibility and biodegradability. The method for preparing the microstructure by the alcohol dehydration principle is simple, and the operation is convenient, so that the method is hopeful to become one of means for quickly preparing the material with the microstructure.
Claims (2)
1. A preparation method of chitosan microspheres with high specific surface area is characterized in that: the method comprises the following steps:
(1) selecting a continuous phase, a disperse phase and a collected phase system: the continuous phase consists of oleic acid containing 1% to 5% by volume of span-80; the dispersed phase is formed by dissolving 1 to 5 mass percent of chitosan and 1 to 2 volume percent of acetic acid in deionized water; the collecting phase is composed of 4-8% of glutaraldehyde, 5-20% of alcohol and 1-5% of tween-20 by volume which are dissolved in deionized water;
(2) selecting a micro-fluidic chip: the chip comprises a dispersed phase inlet, a continuous phase inlet, a dispersed phase liquid channel, a continuous phase liquid channel and an outlet; the disperse phase liquid enters a disperse phase straight channel through a disperse phase inlet, the continuous phase liquid enters a continuous phase liquid channel through a continuous phase inlet, the channel is divided into two symmetrical flow paths towards two sides at the position close to the inlet, and the two continuous phase flow paths are respectively intersected with the disperse phase channel from the left side and the right side at the interface of an outlet channel and the disperse phase channel;
(3) chip channel modification: placing the chip in a vacuum drier for vacuumizing for at least 10min, immediately adding FC40 solution containing 2-4% of 1H,1H,2H, 2H-perfluorooctyl trichlorosilane in volume ratio into the chip, placing the chip at room temperature for 10-30 min, draining the liquid, placing the chip in an oven at 80 ℃ for drying for at least 2H, and taking out the chip; then fixing the chip in a large-size plastic dish through PDMS glue for later use;
(4) preparing microspheres: pouring the collection phase into a large-size plastic dish until the collection phase submerges the outlet channel, and controlling the continuous phase by using an injection pump to fill the whole chip; controlling the dispersed phase by an injection pump, wherein the flow rate ratio of the continuous phase to the dispersed phase is 2:1-20:1, and the size of the obtained chitosan microspheres is gradually reduced along with the increase of the flow rate ratio of the dispersed phase of the continuous phase, and the size range is 250-50 μm;
alcohol is added into the collection phase, and different surface microstructures can be obtained by controlling the alcohol concentration and the dehydration time; the addition of the alcohol can ensure that the continuous phase enters the collecting phase and is dissolved in the collecting phase, thereby accelerating the crosslinking and curing speed of the dispersed phase and ensuring that the crosslinking and curing are more uniform.
2. The preparation method of the chitosan microsphere with high specific surface area as claimed in claim 1, wherein: the size of the chip is 6cm multiplied by 3cm, the channel height is 100-400 μm, the channel widths of the continuous phase and the disperse phase are 1/3, and the width of the outlet channel is consistent with the channel height.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6096344A (en) * | 1995-07-28 | 2000-08-01 | Advanced Polymer Systems, Inc. | Bioerodible porous compositions |
| CN101530765A (en) * | 2009-03-05 | 2009-09-16 | 西北师范大学 | Casein/chitosan compound biological microsphere and preparation method thereof |
| CN101868298A (en) * | 2007-07-06 | 2010-10-20 | 香港大学 | Collagen-based microspheres and methods of preparation and use thereof |
| CN102757517A (en) * | 2011-04-28 | 2012-10-31 | 中国科学院大连化学物理研究所 | Method for preparing quick-responding thermo-sensitive porous microspheres based on microfluidic technology |
| CN103497347A (en) * | 2013-08-26 | 2014-01-08 | 合肥工业大学 | Preparation method of dual functional chitosan microspheres |
| CN104741089A (en) * | 2015-02-15 | 2015-07-01 | 华东理工大学 | Method for preparing crosslinked-chitosan-system azo dye wastewater adsorbent |
| CN105085943A (en) * | 2015-06-18 | 2015-11-25 | 中国科学技术大学 | Polymeric microspheres and preparation method therefor |
| CN105396562A (en) * | 2015-12-18 | 2016-03-16 | 华东理工大学 | Microfluidic preparation method of porous chitosan metal ion adsorbent |
| CN105771929A (en) * | 2016-03-21 | 2016-07-20 | 华东理工大学 | Method for preparing PEI-modified (polyethylenimine-modified) carboxylated chitosan adsorbent for heavy metal wastewater by microfluidics |
-
2018
- 2018-10-24 CN CN201811240572.1A patent/CN111085148B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6096344A (en) * | 1995-07-28 | 2000-08-01 | Advanced Polymer Systems, Inc. | Bioerodible porous compositions |
| CN101868298A (en) * | 2007-07-06 | 2010-10-20 | 香港大学 | Collagen-based microspheres and methods of preparation and use thereof |
| CN101530765A (en) * | 2009-03-05 | 2009-09-16 | 西北师范大学 | Casein/chitosan compound biological microsphere and preparation method thereof |
| CN102757517A (en) * | 2011-04-28 | 2012-10-31 | 中国科学院大连化学物理研究所 | Method for preparing quick-responding thermo-sensitive porous microspheres based on microfluidic technology |
| CN103497347A (en) * | 2013-08-26 | 2014-01-08 | 合肥工业大学 | Preparation method of dual functional chitosan microspheres |
| CN104741089A (en) * | 2015-02-15 | 2015-07-01 | 华东理工大学 | Method for preparing crosslinked-chitosan-system azo dye wastewater adsorbent |
| CN105085943A (en) * | 2015-06-18 | 2015-11-25 | 中国科学技术大学 | Polymeric microspheres and preparation method therefor |
| CN105396562A (en) * | 2015-12-18 | 2016-03-16 | 华东理工大学 | Microfluidic preparation method of porous chitosan metal ion adsorbent |
| CN105771929A (en) * | 2016-03-21 | 2016-07-20 | 华东理工大学 | Method for preparing PEI-modified (polyethylenimine-modified) carboxylated chitosan adsorbent for heavy metal wastewater by microfluidics |
Non-Patent Citations (1)
| Title |
|---|
| 壳聚糖/明胶复合微球的制备;周佳男 等;《粉末冶金材料科学与工程》;20111015;第16卷(第5期);第787-793页 * |
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