CN109988323B - A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature - Google Patents
A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature Download PDFInfo
- Publication number
- CN109988323B CN109988323B CN201810002363.7A CN201810002363A CN109988323B CN 109988323 B CN109988323 B CN 109988323B CN 201810002363 A CN201810002363 A CN 201810002363A CN 109988323 B CN109988323 B CN 109988323B
- Authority
- CN
- China
- Prior art keywords
- channel
- droplet
- polyvinyl alcohol
- catalyst
- segment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 104
- 239000004372 Polyvinyl alcohol Substances 0.000 title claims abstract description 103
- 229920002451 polyvinyl alcohol Polymers 0.000 title claims abstract description 103
- 239000004005 microsphere Substances 0.000 title claims abstract description 76
- 238000002156 mixing Methods 0.000 claims abstract description 73
- 239000012530 fluid Substances 0.000 claims abstract description 62
- 238000004132 cross linking Methods 0.000 claims abstract description 41
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 37
- 239000003054 catalyst Substances 0.000 claims abstract description 32
- 239000007864 aqueous solution Substances 0.000 claims abstract description 26
- 238000007711 solidification Methods 0.000 claims abstract description 19
- 230000008023 solidification Effects 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims description 51
- 239000003921 oil Substances 0.000 claims description 38
- 239000000243 solution Substances 0.000 claims description 35
- 235000019198 oils Nutrition 0.000 claims description 31
- 238000006136 alcoholysis reaction Methods 0.000 claims description 28
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 21
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 claims description 14
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000012815 thermoplastic material Substances 0.000 claims description 11
- 239000002480 mineral oil Substances 0.000 claims description 10
- 235000010446 mineral oil Nutrition 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims description 8
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 8
- 238000005452 bending Methods 0.000 claims description 8
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 229940015043 glyoxal Drugs 0.000 claims description 7
- 229940057995 liquid paraffin Drugs 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 7
- 239000008158 vegetable oil Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 5
- SNRUBQQJIBEYMU-NJFSPNSNSA-N dodecane Chemical group CCCCCCCCCCC[14CH3] SNRUBQQJIBEYMU-NJFSPNSNSA-N 0.000 claims 6
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 2
- 239000002245 particle Substances 0.000 abstract description 22
- 150000001241 acetals Chemical class 0.000 abstract description 2
- 150000002373 hemiacetals Chemical class 0.000 abstract description 2
- 238000005086 pumping Methods 0.000 abstract description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 70
- 230000000052 comparative effect Effects 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000000879 optical micrograph Methods 0.000 description 6
- 238000001878 scanning electron micrograph Methods 0.000 description 6
- 239000002994 raw material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- -1 Polydimethylsiloxane Polymers 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 240000009226 Corylus americana Species 0.000 description 1
- 235000001543 Corylus americana Nutrition 0.000 description 1
- 235000007466 Corylus avellana Nutrition 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910021389 graphene Inorganic materials 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
Images
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
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- 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
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- 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
-
- 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
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
-
- 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
- C08J2329/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal, or ketal radical; Hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Derivatives of such polymer
- C08J2329/02—Homopolymers or copolymers of unsaturated alcohols
- C08J2329/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
本发明提供了一种常温下快速制备单分散聚乙烯醇微球的方法。该方法采用微通道反应器进行，该微通道反应器包括液滴产生区、液滴内流体对流混合区、液滴预交联固化区；液滴内流体对流混合区的通道包括直线通道和非直线通道；该方法包括以下步骤：将聚乙烯醇水溶液、交联剂和催化剂的混合水溶液、油相泵入微通道反应器，形成油包水液滴；使三种组分在液滴内流体对流混合区内进行液滴内快速充分混合，然后在液滴预交联固化区进行预交联反应，形成具有线性半缩醛的凝胶微球；使凝胶微球在收集瓶内深度交联得到缩醛产物，形成具有三维网络结构的聚乙烯醇微球；洗涤、分离所述聚乙烯醇微球，得到单分散聚乙烯醇微球。该微球具有粒径可控、粒度均一、球形度好等优点。
The invention provides a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at normal temperature. The method adopts a micro-channel reactor, the micro-channel reactor includes a droplet generation area, a fluid convective mixing area in the droplet, and a droplet pre-crosslinking solidification area; the channels of the fluid convective mixing area in the droplet include linear channels and non-linear channels. A linear channel; the method includes the following steps: pumping an aqueous solution of polyvinyl alcohol, a mixed aqueous solution of a crosslinking agent and a catalyst, and an oil phase into a microchannel reactor to form water-in-oil droplets; fluid convection of the three components in the droplets In the mixing area, the droplets are quickly and thoroughly mixed, and then the pre-crosslinking reaction is performed in the droplet pre-crosslinking and curing area to form gel microspheres with linear hemiacetal; the gel microspheres are deeply cross-linked in the collection bottle The acetal product is obtained to form polyvinyl alcohol microspheres with a three-dimensional network structure; the polyvinyl alcohol microspheres are washed and separated to obtain monodisperse polyvinyl alcohol microspheres. The microspheres have the advantages of controllable particle size, uniform particle size and good sphericity.
Description
Technical Field
The invention relates to a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at normal temperature, belonging to the technical field of preparation of high molecular polymer microspheres.
Background
The monodisperse polymer microsphere has uniform particle size and regular morphology structure, is widely applied to drug-targeted controllable slow-release carriers, template agents, adsorption separating agents and the like, and particularly has wide application in the fields of medicine, materials, electronics and the like due to excellent chemical and thermal stability, chemical modifiability, biocompatibility and the like of the PVA microsphere. The PVA microspheres prepared by the emulsification crosslinking polymerization of the PVA oligomer have the characteristics of simple preparation process, controllable process, low price of raw materials and the like, and the preparation of the PVA microspheres with uniform particle size and good sphericity by taking the PVA oligomer as the raw material becomes a research hotspot of people.
CN105462915A discloses a preparation method of polyvinyl alcohol microspheres, which comprises dispersing polyvinyl alcohol solution in oil phase into spherical small liquid particles by reverse suspension, then adding cross-linking agent to cross-link polyvinyl alcohol, and obtaining the polyvinyl alcohol microspheres through solidification, washing and screening, wherein the particle size of the microsphere carrier is 60-250 μm. The particle size of the microsphere obtained by the method is difficult to accurately control, the particle size distribution is not uniform, in addition, the process comprises the steps of firstly forming polyvinyl alcohol liquid drops, then adding acid to adjust the pH value, and then adding a cross-linking agent to carry out cross-linking and solidification, and the process added in different steps has the following defects: (1) the acid and the cross-linking agent need to diffuse through an oil-water interfacial film on the surface of the liquid drop and then react with polyvinyl alcohol in the liquid drop, and the diffusion speed is slow, so that the whole curing process is slow; (2) the acid and the cross-linking agent diffuse from outside to inside, so that the cross-linking reaction inside the droplet is also from outside to inside, the outer surface is solidified to form a hard shell, and the acid and the cross-linking agent outside cannot continuously penetrate through the hard shell to react with the polyvinyl alcohol inside the droplet, so that the microsphere structure is not uniform.
CN104857576A discloses a method for preparing polyvinyl alcohol embolism microsphere, which adopts the following process route: (1) preparing a mixed solution of a polyvinyl alcohol aqueous solution and a cross-linking agent aqueous solution as a discrete phase 1, preparing a catalyst aqueous solution as a discrete phase 2, and preparing an organic solvent incompatible with water as a continuous phase; (2) the dispersed phase is divided into liquid drops by utilizing the action of fluid shearing force and interfacial tension in the microchannel; (3) after collecting the liquid drops, standing for 0.5-24 hours at 20-80 ℃ for crosslinking and curing to obtain polyvinyl alcohol particles; (4) washing with organic solvent such as alkane, petroleum ether, ethyl acetate, etc. for 12-48 hr, and drying under vacuum drying, freeze drying or spray drying to obtain the final product. Although the method can prepare PVA microspheres with uniform granularity and good sphericity, the curing time is too long, the curing temperature is high, and the washing process is complex.
Therefore, the prior art can not realize the rapid and convenient preparation of the PVA microspheres at room temperature, so that the further improvement of the preparation process and the research and development of the preparation method for rapidly and conveniently preparing the monodisperse PVA microspheres at room temperature have important significance.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at normal temperature, which is carried out by adopting a microchannel reactor, and realizes rapid and controllable preparation of high polymer microspheres at room temperature by arranging a fluid convection mixing zone with special properties in liquid.
In order to achieve the aim, the invention provides a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at normal temperature, which is carried out by adopting a microchannel reactor, wherein the microchannel reactor comprises a liquid drop generating area, a convection mixing area of fluid in the liquid drops and a liquid drop pre-crosslinking curing area;
the channels of the fluid convection mixing zone in the liquid drop comprise a linear channel and a nonlinear channel, and preferably, the nonlinear channel is an S-shaped curved channel, a Z-shaped channel or other irregularly-shaped curved channels;
the method comprises the following steps:
pumping a polyvinyl alcohol aqueous solution serving as a first dispersed phase, a cross-linking agent and catalyst mixed aqueous solution serving as a second dispersed phase and an oil phase serving as a continuous phase into a microchannel reactor, and forming water-in-oil droplets containing polyvinyl alcohol, the cross-linking agent and a catalyst component in a droplet generation area;
Three components of polyvinyl alcohol, a cross-linking agent and a catalyst are quickly and fully mixed in the liquid drops in a fluid convection mixing zone in the liquid drops, and then a pre-crosslinking reaction is carried out in a liquid drop pre-crosslinking curing zone to form gel microspheres with linear hemiacetal;
deeply crosslinking the gel microspheres in a collecting bottle to obtain an acetal product, and forming polyvinyl alcohol microspheres with a three-dimensional network structure;
and washing and separating the polyvinyl alcohol microspheres to obtain the monodisperse polyvinyl alcohol microspheres.
In the microchannel reactor, preferably, the convective mixing zone of the fluid in the droplets satisfies the following condition:
L＝L1+L2；
wherein L is the total length of the convection mixing zone of the fluid in the liquid drop and is expressed by m; l is1Is the length of the straight channel, and the unit is m; l is2Is the linear length of the non-linear channel in m.
In the microchannel reactor of the invention, the droplet generation area is used for mixing the dispersed phases, the continuous phases and the like with each other to form droplets, and the channel of the droplet generation area can be a T-shaped microchannel, a flow confocal channel or a co-flow channel. The injection of the dispersed phase and the continuous phase can be performed by a micro-syringe pump.
In the microchannel reactor of the invention, the in-droplet fluid convection mixing zone is used to provide rapid and thorough mixing of the components in the droplets produced in the droplet-producing zone. At the beginning of the convection mixing zone of the fluid in the liquid drop, the diameter of the linear channel is suddenly increased relative to the diameter of the channel in the liquid drop generating zone, and by utilizing the sudden expansion of the pipe orifice (pipe diameter), boundary layer separation can be generated to generate vortex, so that the fluid in the liquid drop is promoted to be mixed; in the non-linear channel part, the flow velocity of the fluid inside and outside the liquid drop is different due to the resistance of the wall surface to the fluid at each bending inflection point, and the fluid inside the liquid drop generates vortex to promote mixing. The convection mixing area of the fluid in the liquid drop can ensure that the fluid in the liquid drop is uniformly mixed, and the liquid drop is not broken and is not fused. Merged means that two or three droplets merge into one.
In the microchannel reactor of the invention, the droplet pre-crosslinking curing zone is used for pre-curing the droplets, and the channel section can be square, round, oval or other shapes. The liquid drop pre-crosslinking curing zone can ensure that the fluid in the liquid drop is just pre-cured and has certain forming but is not cured completely (if the curing is complete, the cured microspheres are easy to deposit in the channel and block the channel), and the liquid drop can smoothly flow into the collecting unit from the curing zone, so that the reaction is smoothly carried out.
The microchannel reactor provided by the present invention may further comprise a collection and solidification zone for collecting the pre-crosslinked and solidified droplets and completely crosslinking them to obtain microspheres. The collection solidification area can be provided with a collection bottle, oil phase fluid is pre-filled in the collection bottle, the collection tube extends into the position below the liquid level of the collection liquid, and the collection bottle mouth is sealed.
In the microchannel reactor of the invention, the nonlinear channel part of the convection mixing zone of the fluid in the droplet can be an S-shaped curved channel, a Z-shaped channel or other irregularly-shaped curved channels. The length of the convection mixing zone of the fluid in the droplets is related to the number of times the channel direction changes occur, i.e. the number of bends. When the channel direction changes once, the chaotic convection of the fluid in the liquid drops can occur in the liquid drops, so that the mixing of the fluid in the liquid drops is enhanced, the mixing efficiency is improved, and the time for achieving complete mixing is shortened. Therefore, the bending times are more, and the length of the channel in the mixing area is short; the bending times are less, and the channel length of the mixing zone is long.
In the microchannel reactor of the present invention, the S-shaped curved channel preferably consists of N arc-shaped curved sections connected end to end, and the value of N is not limited to an integer, and the specific value can be determined according to the required length of the S-shaped curved channel. Preferably, the S-bend channel satisfies the following condition:
R1is the outer diameter of the arc-shaped bending part and has the unit of m; r1Preferably 200 and 2000 microns;
R2is the inner diameter of the arc-shaped bending part and has the unit of m; r2Preferably 100-;
theta is the central angle for the arcuate bend, preferably 90 deg. < theta < 360 deg., such as 135 deg., 180 deg., or 235 deg., for the S-bend path shown in fig. 1a, 1b, 1c, respectively.
In the microchannel reactor of the present invention, the Z-channel is preferably composed of M Z-bends connected end-to-end, where the Z-shape is not limited to
This general Z-shape, with extensions, is also possible, preferably each Z-bend is composed of a first section, a second section, a third section and a fourth section, and the first section of the first Z-bend can directly serve as a straight channel for the convective mixing zone of the fluid in the droplet. The total length of the non-linear channel can be determined according to actual needs, and therefore, the last Z-shaped bent part can be complete, and only comprises 1-3 of the first segment, the second segment and the third segment.
According to the preferred embodiment of the present invention, preferably, the first segment is perpendicular to the second segment or at an angle of 90 to 150 °, the second segment is perpendicular to the third segment or at an angle of 90 to 150 °, and the third segment is perpendicular to the fourth segment or at an angle of 90 to 150 °; the included angle is preferably 120 DEG, 150 DEG, more preferably 90 DEG, 120 DEG, 135 DEG or 150 DEG; the vertical case may be:
the corresponding Z-bend path is shown in FIG. 2; the angled condition may be:
the specific angle is not limited to the angle shown in the above figures.
According to a preferred embodiment of the present invention, the lengths of the first section, the second section, the third section and the fourth section of the Z-shaped bending part are respectively 200-.
According to a preferred embodiment of the present invention, the Z-shaped bent portion satisfies the following condition: the included angle between the segments is 90 deg., and the lengths of the first, second, third and fourth segments are equal.
In the microchannel reactor of the invention, the two-phase fluid is basically in laminar flow in the straight channel, the mixing is slow, and the channel is designed into the curved channel, so that the fluid can generate disturbance when flowing through the curved channel, and the mixing is promoted.
In the microchannel reactor of the invention, preferably, the width of the channel of the droplet generation zone is 50-500 micrometers, the width of the channel of the fluid convection mixing zone in the droplet is 100-.
In the microchannel reactor of the invention, preferably, the heights of the channels of the droplet generation zone, the fluid convection mixing zone in the droplets and the droplet pre-crosslinking curing zone are the same and are all 50-1500 micrometers.
In the microchannel reactor of the present invention, preferably, the length of the channel of the droplet generation zone is 100-500 μm.
In the microchannel reactor of the invention, at the beginning of the fluid convection mixing zone in the droplets, the mixing of the fluid in the droplets can be promoted by using the sudden expansion of the pipe diameter, and preferably, the ratio of the width of the channel of the fluid convection mixing zone in the droplets to the width of the channel of the droplet generation zone is 1-4: 1 and not 1:1, can be controlled to be 1.5-4:1, more preferably 2-3: 1.
in the microchannel reactor of the present invention, preferably, the ratio of the width of the channel of the droplet pre-crosslinking solidification zone to the width of the channel of the fluid convection mixing zone in the droplet is 1 to 20: 1, more preferably 1 to 15: 1.
In the microchannel reactor of the present invention, preferably, the ratio of the height of the channel to the width of the channel of the droplet-generating zone is 0.3 to 1.5: 1.
in the microchannel reactor of the present invention, preferably, the ratio of the height of the channel to the width of the channel of the convective mixing zone within the droplet is 0.5 to 1.5: 1.
in the microchannel reactor of the invention, preferably, the length of the channel of the fluid convection mixing zone in the droplet is 1000-.
In the microchannel reactor of the invention, the length L3 of the channel of the droplet pre-crosslinking curing zone is preferably 1000-10000 μm.
In the microchannel reactor of the invention, the material used for the channels of each part can be Polydimethylsiloxane (PDMS) and can also be PMMA.
In the method provided by the invention, preferably, the mass concentration of the polyvinyl alcohol aqueous solution is 2-10%; in the mixed water solution of the cross-linking agent and the catalyst, the mass concentration of the cross-linking agent is 2-10%, and the concentration of the catalyst is 0.1-3 mol/L; the oil phase is oil immiscible with water, and contains 1-10% of surfactant.
Preferably, the first dispersed phase solution further contains a thermoplastic material as a pore-forming agent for preparing the porous microspheres, wherein the thermoplastic material may comprise one or a combination of polyethylene glycol, polyvinyl alcohol with low alcoholysis degree (preferably alcoholysis degree lower than 86%) and water-soluble starch.
In the method provided by the invention, preferably, the flow rates of the first dispersed phase and the second dispersed phase are respectively 0.1-4mL/h and are the same; the flow rate of the continuous phase is 1-20 mL/h. Water-in-oil droplets are formed by shearing of the continuous phase.
In the method provided by the invention, the adopted polyvinyl alcohol is a polyvinyl alcohol oligomer, and preferably, the alcoholysis degree of the polyvinyl alcohol is more than 85%, and the number average molecular weight is more than 60000.
In the method provided by the invention, preferably, the cross-linking agent is one of glutaraldehyde, glyoxal, formaldehyde and the like.
In the method provided by the invention, preferably, the catalyst is a water-soluble protonic acid.
In the method provided by the invention, preferably, the pH value of the mixed aqueous solution of the cross-linking agent and the catalyst is 0.5-5.
In the method provided by the invention, preferably, the oil phase is one or a combination of several of the nonvolatile alkane, liquid paraffin, mineral oil, vegetable oil and the like, and is more preferably dodecane and/or hexadecane.
In the method provided by the invention, preferably, the surfactant is one or a combination of several of Span80, DC0749, EM90 and Tween 20.
The first dispersed phase solution can also contain graphene, magnetic substances, carbon powder, carbon nanotubes and other substances and is used for preparing functional polyvinyl alcohol microspheres. The first dispersed phase solution can also contain a medicament insensitive to acid to prepare medicament-loaded polyvinyl alcohol microspheres.
The technical scheme provided by the invention mainly has the following beneficial effects:
(1) the micro-channel reactor adopted by the invention has simple and feasible structure, adjustable and controllable size, and convenient regulation and control of the size of the prepared microsphere.
(2) The convection mixing area of the fluid in the liquid drops arranged in the microchannel reactor adopted by the invention can ensure that the fluid in each liquid drop can be completely mixed quickly within a few seconds, and the fluid in the liquid drops can be completely mixed without pre-crosslinking reaction in the mixing channel to block the channel and influence the smooth reaction by regulating and controlling the length of the channel of the convection mixing area of the fluid in the liquid drops.
(3) The liquid drop pre-crosslinking curing area arranged in the microchannel reactor adopted by the invention can cause the components in the liquid drops to generate pre-crosslinking reaction to form a basic gel structure, and provides necessary precondition for the prepared microspheres to keep better monodispersity and perfect sphericity.
(4) The micro-channel reactor adopted by the invention can realize low energy consumption and continuous operation, and if a plurality of micro-channel reactors are simply connected in parallel, the yield can be rapidly increased, the production efficiency is improved, and no amplification effect exists.
In conclusion, the technical scheme provided by the invention can overcome the defects of complex process, difficult accurate control of product granularity, irregular shape and the like in the prior art, and has the advantages of simple and rapid preparation process, controllable particle size, uniform granularity, good sphericity and the like.
Drawings
Fig. 1a, 1b and 1c are schematic views of corresponding S-shaped curved channels at different angles.
FIG. 2 is a schematic diagram of a microchannel reactor with a Z-bend channel.
FIG. 3 is a schematic diagram of the microchannel reactor used in comparative example 3.
FIG. 4 is a schematic structural view of a microchannel reactor used in example 1.
FIG. 5 is a scanning electron micrograph of the monodisperse polyvinyl alcohol microspheres of example 1, with a 100 μm scale.
FIG. 6 is a scanning electron micrograph of the monodisperse polyvinylalcohol microsphere of example 2, which is shown to have a scale of 200. mu.m.
FIG. 7 is a scanning electron micrograph of hazelnut-like polyvinyl alcohol microspheres of example 3, with a scale of 200. mu.m.
FIG. 8 is a scanning electron micrograph of the polyvinyl alcohol microspheres of example 4, with a scale of 500. mu.m.
FIG. 9 is an optical micrograph of polyvinyl alcohol microspheres of comparative example 3, with a 200 μm scale.
FIG. 10 is an optical micrograph of polyvinyl alcohol gel microspheres of comparative example 4, with a 500 μm scale.
FIG. 11 is an optical micrograph of the polyvinyl alcohol gel microspheres of comparative example 4 after drying, with a 200 μm scale.
Detailed Description
The technical solutions of the present invention will be described in detail below in order to clearly understand the technical features, objects, and advantages of the present invention, but the present invention is not limited to the practical scope of the present invention.
Example 1
This example provides a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature, and the structure of the microchannel reactor used in the method is shown in fig. 4.
The microchannel reactor comprises a droplet generation area, a fluid convection mixing area in the droplets and a droplet pre-crosslinking curing area, wherein:
the width of the channel of the droplet generation area is 100 micrometers, the height of the channel is 150 micrometers, the channel is a flow focusing type microchannel and comprises two disperse phase channels and two continuous phase channels;
the length L of the channel of the convection mixing zone of the fluid in the droplet is 6654 microns and the width W 1Is 200 microns and has a height of 150 microns,
length L of channel of droplet pre-crosslinking solidification zone34000 micrometers and width W21000 microns and a height of 150 microns;
the channel of the fluid convection mixing zone in the liquid drop comprises a linear channel and a nonlinear channel, wherein the nonlinear channel is an S-shaped bent channel; length L of straight passage11000 microns, length L of the nonlinear channel25654 μm;
the S-shaped curved passage comprises 3 regular end-to-end arc-shaped curved parts, and the outer diameter R of each arc-shaped curved part1700 μm, inner diameter R 2500 microns, corresponding to a central angle theta of 180 deg..
The method for rapidly preparing the monodisperse polyvinyl alcohol microspheres at normal temperature provided by the embodiment is carried out according to the following steps:
adding 2.0g cetyl/polypropylene glycol-10/1 dimethyl siloxane (EM90) into a beaker containing 100mL mineral oil, slowly stirring by adopting a magnetic stirring mode, and then filtering to obtain a continuous phase solution;
dissolving 2 g of polyvinyl alcohol with alcoholysis degree of 97% and molecular weight of 10 ten thousand in 100 g of water to obtain a first dispersed phase solution;
mixing 10 g of 50% glutaraldehyde solution by mass and 8 ml of hydrochloric acid with the molar concentration of 10mol/L into 92 g of water to obtain a second dispersed phase solution;
Respectively filling the continuous phase solution, the first dispersed phase solution and the second dispersed phase solution into 20mL syringes, placing the syringes on a micro-injection pump, connecting the syringes with a microchannel reactor, setting the flow rates of the first dispersed phase solution and the second dispersed phase solution to be 0.5mL/h and the flow rate of the continuous phase solution to be 5mL/h, enabling the dispersed phase and the continuous phase to meet at a channel intersection of a droplet generation area in the microchannel reactor, continuously generating water-in-oil droplets with uniform size, and continuously generating water-in-oil droplets with the uniform size, wherein the solution components in the droplets are polyvinyl alcohol, glutaraldehyde and hydrochloric acid;
after the liquid drops pass through a fluid convection mixing zone and a liquid drop pre-crosslinking curing zone in the liquid drops, curing the liquid drops in a collecting bottle for 20 minutes to obtain polyvinyl alcohol microspheres;
after washing the polyvinyl alcohol microspheres for 5 times by using absolute ethyl alcohol and ultrasonic waves, the monodisperse polyvinyl alcohol microspheres are obtained, the particle size is 40 +/-2 microns, the size deviation of the microspheres is 1.26 percent, and a scanning electron microscope picture is shown in figure 5, so that the microspheres are uniform in particle size and good in sphericity.
Comparative example 1
This comparative example provides a microchannel reactor having substantially the same structure as the microchannel reactor of example 1, except that: the channels of the convective mixing zone within the droplet had a length of 25000 microns, a width of 200 microns, and a height of 150 microns.
Monodisperse polyvinylalcohol microspheres were prepared according to the procedure of example 1 using the microchannel reactor provided in this comparative example, with the following differences: when the experiment is carried out for 10 minutes, solid matters are blocked in the channel of the mixing zone, and the polyvinyl alcohol fiber which is linear is taken out and observed. The comparative example shows that the length of the channel of the fluid convection mixing zone in the droplets is far longer than that of example 1, and the results of this comparative example show that the length of the channel of the fluid convection mixing zone in the droplets is too long and is not suitable for preparing microspheres.
Comparative example 2
This comparative example provides a microchannel reactor having substantially the same structure as the microchannel reactor of example 1, except that: the channel of the convective mixing zone within the droplet was 10000 microns in length, 1000 microns in width and 150 microns in height.
Monodisperse polyvinylalcohol microspheres were prepared according to the procedure of example 1 using the microchannel reactor provided in this comparative example, with the following differences: at 15 minutes into the experiment, solid material was trapped in the connecting conduit between the pre-crosslinking solidification zone and the collection bottle and was removed and observed as linear polyvinyl alcohol fibers. The comparative example has a larger width of the channel of the in-droplet fluid convection mixing zone than example 1 and the results of this comparative example show that too wide a width of the channel of the in-droplet fluid convection mixing zone is not suitable for the preparation of microspheres.
Example 2
This example provides a method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature, and the structure of the microchannel reactor used in the method is shown in fig. 2.
The microchannel reactor comprises a droplet generation area, a fluid convection mixing area in the droplets, a droplet pre-crosslinking solidification area and a collection bottle (not shown in the figure), wherein:
the width of the channel of the droplet generation area is 300 micrometers, the height of the channel is 300 micrometers, the channel is a T-shaped microchannel and comprises two dispersed phase channels and two continuous phase channels;
the channels of the convective mixing zone within the droplet were 13000 microns in length, 700 microns in width and 300 microns in height,
the length of the channel of the liquid drop pre-crosslinking curing zone is 6000 microns, the width is 5600 microns, and the height is 300 microns;
the Z-shaped bent channel comprises 3 regular Z-shaped bent parts which are connected end to end, the Z-shaped bent parts comprise a first section, a second section, a third section and a fourth section which are sequentially connected, the adjacent sections are mutually vertical, and the lengths of the four sections are respectively 1000 micrometers, 1300 micrometers, 733 micrometers and 1300 micrometers.
The method for rapidly preparing the monodisperse polyvinyl alcohol microspheres at normal temperature provided by the embodiment is carried out according to the following steps:
Adding 2.0g of cetyl polyethylene glycol (EM90) into a beaker containing 100mL of mineral oil, slowly stirring in a magnetic stirring manner, and then filtering to obtain a continuous phase solution;
dissolving 2 g of polyvinyl alcohol with alcoholysis degree of 97% and molecular weight of 10 ten thousand in 100 g of water to obtain a first dispersed phase solution;
mixing 10 g of 50% glutaraldehyde solution by mass and 8 ml of hydrochloric acid with the molar concentration of 10mol/L into 92 g of water to obtain a second dispersed phase solution;
respectively filling the continuous phase solution, the first dispersed phase solution and the second dispersed phase solution into 20mL syringes, placing the syringes on a micro-injection pump, connecting the syringes with a microchannel reactor, setting the flow rates of the first dispersed phase solution and the second dispersed phase solution to be 0.5mL/h and the flow rate of the continuous phase solution to be 2mL/h, enabling the dispersed phase and the continuous phase to meet at a channel intersection of a droplet generation area in the microchannel reactor, continuously generating water-in-oil droplets with uniform size, and continuously generating water-in-oil droplets with the uniform size, wherein the solution components in the droplets are polyvinyl alcohol, glutaraldehyde and hydrochloric acid;
after the liquid drops pass through a fluid convection mixing zone and a liquid drop pre-crosslinking curing zone in the liquid drops, curing the liquid drops in a collecting bottle for 20 minutes to obtain polyvinyl alcohol microspheres;
After washing the polyvinyl alcohol microspheres for 5 times by using absolute ethyl alcohol and ultrasonic waves, the monodisperse polyvinyl alcohol microspheres are obtained, the particle size is 180 +/-10 micrometers, and a scanning electron microscope picture is shown in figure 6, so that the microspheres are uniform in particle size and good in sphericity.
Example 3
Monodisperse polyvinyl alcohol microspheres were prepared according to the procedure in example 2 using the microchannel reactor provided in example 2, with the exception that: the preparation of the continuous phase solution is as follows: 5.0 grams of span 80 was added to 100mL of mineral oil and mixed well as a continuous phase solution. The polyvinyl alcohol microspheres obtained by the experiment are in a hazelnut shape, and the particle size is 160 +/-10 microns. The scanning electron micrograph is shown in FIG. 7.
Example 4
This example provides a microchannel reactor, which has a structure substantially the same as that of the microchannel reactor in example 2, except that: the channels of the convective mixing zone within the droplet were 3000 microns in length, 700 microns in width and 300 microns in height.
The monodisperse polyvinyl alcohol microspheres prepared by the microchannel reactor provided in this example were irregular particles with concave-convex surfaces, and the particle size was 180 ± 40 μm, according to the procedure in example 4. The scanning electron micrograph is shown in FIG. 8.
Comparative example 3
The comparative example provides a microchannel reactor, which only has a droplet generation area and has no other two functional areas, the structure is shown in figure 3, other solution preparation and droplet generation fluid flow rate control parameters are the same as those in example 1, the droplets are directly introduced into a collection bottle through a conduit after being generated, crosslinking and curing are carried out for 72h, the droplets are demulsified and partially condensed together in the curing process, the surface of microsphere particles is rough, the particle size distribution is not uniform, and part of the particles are adhered together after the curing is finished, and the optical micrograph is shown in figure 9.
Comparative example 4
The comparative example provides a preparation method of monodisperse polyvinyl alcohol microspheres, wherein the polyvinyl alcohol is prepared into an aqueous solution with the mass percentage of 3% by adopting raw materials with the alcoholysis degree of 85% and the molecular weight of 30000-70000, all other parameters are the same as those in example 1, and the transparent polyvinyl alcohol gel with uniform particle size is obtained after being introduced into a collection bottle through a conduit and being crosslinked and cured for 24 hours, the size of the transparent polyvinyl alcohol gel is 385 +/-10 microns, and a microscopic optical micrograph thereof is shown in figure 10. The crosslinking curing was continued for 120h while the polyvinyl alcohol gel was still transparent, and the optical micrograph after drying is shown in FIG. 11.
Compared with the comparative example 3, the embodiment 2 reasonably designs the mixing region and the curing and forming region of the microreactor, so that various components in the liquid drops can be quickly and uniformly mixed, the curing rate and the curing degree of each liquid drop in each direction are consistent when each liquid drop is cured, and the microspheres with uniform particle size and good sphericity are obtained.
Compared with the comparative example 4, the polyvinyl alcohol with alcoholysis degree of more than 85% and molecular weight of more than 70000 is adopted as the raw material in the example 2, and the polyvinyl alcohol reacts with glutaraldehyde to obtain higher crosslinking degree, so that the surface of the dried microsphere is smoother and the sphericity is better.
Claims (66)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810002363.7A CN109988323B (en) | 2018-01-02 | 2018-01-02 | A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810002363.7A CN109988323B (en) | 2018-01-02 | 2018-01-02 | A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109988323A CN109988323A (en) | 2019-07-09 |
| CN109988323B true CN109988323B (en) | 2021-10-08 |
Family
ID=67128610
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810002363.7A Active CN109988323B (en) | 2018-01-02 | 2018-01-02 | A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109988323B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114144465B (en) * | 2019-07-30 | 2024-02-09 | 株式会社可乐丽 | Resin powder and manufacturing method thereof |
| CN115038517A (en) * | 2020-01-21 | 2022-09-09 | 苏州恒瑞宏远医疗科技有限公司 | Reaction device and processing method thereof, and preparation equipment and preparation method of embolism microsphere |
| CN115245589B (en) * | 2021-06-25 | 2024-08-20 | 苏州浩微生物医疗科技有限公司 | Novel degradable embolism microsphere with controllable particle size and preparation method thereof |
| CN116003669B (en) * | 2021-10-21 | 2025-01-17 | 中国石油化工股份有限公司 | Polyvinyl alcohol having excellent gel resistance |
| CN114146648B (en) * | 2021-12-03 | 2024-10-22 | 四川大川合颐生物科技有限公司 | System and method for recycling cross-linking liquid in microsphere production based on microfluidic technology |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007150030A3 (en) * | 2006-06-23 | 2008-07-17 | Massachusetts Inst Technology | Microfluidic synthesis of organic nanoparticles |
| CN104173294A (en) * | 2014-08-25 | 2014-12-03 | 重庆大学 | Method for preparing PVA microspheres based on microfluidic drop formation technology |
| CN104829851A (en) * | 2015-04-24 | 2015-08-12 | 山东省科学院能源研究所 | Preparation method of mono-dispersed gelatin embolic microsphere with precisely-controlled particle size |
| CN106214489A (en) * | 2016-09-09 | 2016-12-14 | 山东省科学院能源研究所 | A kind of double-deck emulsion droplet, medicine carrying microballoons and preparation method thereof and device |
| CN107353429A (en) * | 2017-07-21 | 2017-11-17 | 中国工程物理研究院激光聚变研究中心 | The method for preparing polymer hollow microsphere using three-dimensional random flow field |
-
2018
- 2018-01-02 CN CN201810002363.7A patent/CN109988323B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007150030A3 (en) * | 2006-06-23 | 2008-07-17 | Massachusetts Inst Technology | Microfluidic synthesis of organic nanoparticles |
| CN104173294A (en) * | 2014-08-25 | 2014-12-03 | 重庆大学 | Method for preparing PVA microspheres based on microfluidic drop formation technology |
| CN104829851A (en) * | 2015-04-24 | 2015-08-12 | 山东省科学院能源研究所 | Preparation method of mono-dispersed gelatin embolic microsphere with precisely-controlled particle size |
| CN106214489A (en) * | 2016-09-09 | 2016-12-14 | 山东省科学院能源研究所 | A kind of double-deck emulsion droplet, medicine carrying microballoons and preparation method thereof and device |
| CN107353429A (en) * | 2017-07-21 | 2017-11-17 | 中国工程物理研究院激光聚变研究中心 | The method for preparing polymer hollow microsphere using three-dimensional random flow field |
Non-Patent Citations (2)
| Title |
|---|
| A microfluidic device for the characterisation of embolisation with polyvinyl alcohol beads through biomimetic bifurcations;Dario Carugo;《BIOMEDICAL MICRODEVICES》;20111011;第14卷(第01期);第153-163页 * |
| 利用微流控装置制备微球的研究进展;张艳 等;《过程工程学报》;20091015;第09卷(第05期);第1028-1034页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109988323A (en) | 2019-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109988323B (en) | A method for rapidly preparing monodisperse polyvinyl alcohol microspheres at room temperature | |
| CN109985588B (en) | Microchannel reactor | |
| Chen et al. | Advanced microfluidic devices for fabricating multi‐structural hydrogel microsphere | |
| Cai et al. | Anisotropic microparticles from microfluidics | |
| CN101279232B (en) | Preparation of microballoons based on microfluid | |
| Shah et al. | Fabrication of monodisperse thermosensitive microgels and gel capsules in microfluidic devices | |
| Serra et al. | A predictive approach of the influence of the operating parameters on the size of polymer particles synthesized in a simplified microfluidic system | |
| Seo et al. | Continuous microfluidic reactors for polymer particles | |
| CN101376093B (en) | A kind of preparation method of coaxial microchannel reactor | |
| Kim et al. | Fabrication of monodisperse gel shells and functional microgels in microfluidic devices | |
| CN106214489A (en) | A kind of double-deck emulsion droplet, medicine carrying microballoons and preparation method thereof and device | |
| He et al. | A modified microfluidic chip for fabrication of paclitaxel-loaded poly (l-lactic acid) microspheres | |
| Frank et al. | Synthesis of polymer Janus particles with tunable wettability profiles as potent solid surfactants to promote gas delivery in aqueous reaction media | |
| CN106040117B (en) | The method that monodispersity calcium alginate microsphere is prepared based on emulsion liquid membrane mass transfer | |
| CN104288122B (en) | Biodegradable PLGA/PCL composite micro-capsules and preparation method thereof | |
| Zhang et al. | A microfluidic approach to fabricate monodisperse hollow or porous poly (HEMA–MMA) microspheres using single emulsions as templates | |
| CN113429554B (en) | Polymer microsphere, preparation method and drug-loading application thereof | |
| US20090273105A1 (en) | Method and system for performing an interfacial reaction in a microfluidic device | |
| Yamada et al. | Multiphase microfluidic processes to produce alginate-based microparticles and fibers | |
| Pullagura et al. | Coupling electrohydrodynamics with photopolymerization for microfluidics-based generation of polyethylene glycol diacrylate (PEGDA) microparticles and hydrogels | |
| Zhang et al. | Controllable microfluidic fabrication of microstructured functional materials | |
| CN208177428U (en) | A kind of micro passage reaction | |
| WO2021023041A1 (en) | Preparation method for non-spherical hydrogel microparticle embolic agent | |
| Saqib et al. | Microfluidic methods in janus particle synthesis | |
| CN206404046U (en) | A kind of device for preparing double-deck emulsion droplet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |