CN113070108A - Preparation method of patterned hydrogel particles and microfluidic device - Google Patents
Preparation method of patterned hydrogel particles and microfluidic device Download PDFInfo
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- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
Abstract
The invention provides a preparation method of patterned hydrogel particles and a microfluidic device, comprising the following steps: the micro-fluidic chip glue supply system comprises a micro-fluidic chip, wherein the micro-fluidic chip inputs a dispersed phase solution to form a laminar flow structure; and the capillary jetting system is used for inputting the dispersed phase solution with the laminar structure, and introducing gas to cut the dispersed phase solution to form the hydrogel particles with the multi-compartment structure. The pneumatic driving device of the invention is used as a power source to complete the cutting preparation of dispersed phase droplets, is green and safe, and can flexibly and variably manufacture hydrogel particles with various structures.
Description
Technical Field
The invention relates to the technical field of biological materials, in particular to a preparation method of patterned hydrogel particles and a microfluidic device.
Background
In recent years, there has been much interest in configuring multi-purpose hydrogel materials as heterogeneous particles in biomedical applications. These hydrogel microparticles having anisotropy have been used to solve problems such as drug loading, cell culture, food additives, and controlled micro-reactions. In addition, more complex applications present challenges to higher order hydrogel structures, and the precise gel spacing arrangement facilitates broadening the application range of hydrogel droplets, thereby helping people to meet more complex challenges.
Patterned hydrogel microparticle preparation techniques are still imperfect and four methods are commonly used: droplet technology based on coaxial capillary microfluidic systems; droplet technology based on centrifugal systems; flow lithography techniques and electrohydrodynamic jetting techniques. These techniques can be used to produce patterned microparticles, but these techniques are often difficult to flexibly design the structure of the compartments within the microparticles, such as an asymmetric structural distribution within the microparticle. In addition these techniques include several non-biocompatible manipulations that stimulate the culture of damaged cells, such as stimulation of the acidic environment during fluid cutting, mechanical damage of centrifugation devices, and photodamage and electrokinetically driven electrical stimulation of photolithography.
For this reason, there is a pressing need to develop simpler green safe patterned microparticle fabrication techniques for breaking through the complex biological hydrogel microparticle fabrication.
Disclosure of Invention
In order to solve the problems in the prior art and meet the future development requirements in the field, the invention provides a preparation method of patterned hydrogel particles and a microfluidic device.
In order to solve the above problems, the present invention provides a microfluidic device comprising:
the micro-fluidic chip glue supply system comprises a micro-fluidic chip, wherein the micro-fluidic chip inputs a dispersed phase solution to form a laminar flow structure;
and the capillary jetting system is used for inputting the dispersed phase solution with the laminar structure, and introducing gas to cut the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
Optionally, the microfluidic chip glue supply system further comprises a glass slide and a PDMS sheet, the microfluidic chip is placed on the glass slide, the microfluidic chip is provided with a dispersed phase inlet and a dispersed phase outlet, the dispersed phase outlet is perpendicular to the microfluidic chip, and the PDMS sheet is located on the glass slide and surrounds the microfluidic chip to serve as a barrier for a dispersed phase solution.
Optionally, the capillary jetting system includes an input capillary, an output capillary, and a connecting member, the input capillary is communicated with the dispersed phase outlet, the dispersed phase solution flows into the input capillary through the dispersed phase outlet, one end of the connecting member is connected to the input capillary, the other end of the connecting member is connected to the output capillary, the input capillary and the output capillary are coaxial, the connecting member is provided with a gas inlet, and the dispersed phase solution flowing out of the input capillary is cut by gas to form hydrogel particles with a multi-compartment structure.
Optionally, the connection is a three-way valve.
Optionally, the microfluidic chip is coaxially connected with a transverse axis of the input capillary to form a dispersed phase microchannel, and a vertical axis of the input capillary is coaxial with a vertical axis of the output capillary.
Optionally, the capillary tube spraying system further comprises an auxiliary capillary tube, an outer wall of the auxiliary capillary tube is in clearance fit with the connecting piece, an inner wall of the auxiliary capillary tube is in clearance fit with the input capillary tube, the connecting piece is in clearance fit with the output capillary tube, and vertical axes of the input capillary tube and the output capillary tube are coaxial through the connecting piece and the auxiliary capillary tube.
Optionally, the capillary spray system further comprises a gas flow controller for controlling the flow rate of the cutting dispersed phase solution gas.
Optionally, the system comprises a plurality of microfluidic chips and a plurality of input capillaries, which form a microchannel of multiple dispersed phases, and controls the input of multiple dispersed phase solutions and the internal structure of the patterned hydrogel particles through different arrangements of the dispersed phase microchannels.
Optionally, the microfluidic chip has two dispersed phase input ports symmetrically disposed with respect to the dispersed phase output port.
In order to solve the above problems, the present invention also provides a method for preparing patterned hydrogel microparticles using the above microfluidic device, comprising:
injecting the dispersion phase solution into a micro-fluidic chip of a micro-fluidic chip glue supply system to form a laminar flow structure;
the dispersed phase solution of the laminar flow structure of the microfluidic chip glue supply system enters a capillary tube injection system;
and introducing gas into the capillary spraying system, and cutting the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
The invention relates to a microfluidic device which is prepared by pneumatically driving patterned hydrogel particles, the microfluidic device is constructed by adopting an integrated assembly method and is simple and easy to obtain, an upstream microfluidic chip of the device realizes the preparation of patterned heterogeneous particles with more complex structures by the arrangement of multiple dispersed phases and input control, the device cuts input continuous glue solution by utilizing pressure gas at the downstream, and the size of liquid drops is effectively and accurately regulated and controlled by the regulation of a gas flow controller. Provides a preparation method of green and safe patterned hydrogel particles, which is suitable for 3D cell culture in the field of biomedicine.
Drawings
The invention will be described in more detail hereinafter on the basis of embodiments and with reference to the accompanying drawings. Wherein:
FIG. 1 is a schematic view of a microfluidic device according to the present invention;
FIG. 2 is a schematic diagram of an assembly of a capillary spray system;
FIG. 3 is a schematic view of a connection structure between a micro-fluidic chip glue supply system and an input capillary;
FIG. 4 is a schematic view of one embodiment of an internal flow path of a microfluidic device according to the present invention;
FIG. 5 is a schematic diagram of a microfluidic chip design for dual-chamber hydrogel particle fabrication and corresponding dual-chamber hydrogel particles;
FIG. 6 is a schematic diagram of a microfluidic chip design for preparation of six-chamber hydrogel particles and corresponding six-chamber hydrogel particles;
FIG. 7 is a schematic diagram of a microfluidic chip design for preparation of asymmetric three-chamber hydrogel particles and corresponding asymmetric three-chamber hydrogel particles;
description of reference numerals: 1. a micro-fluidic chip glue supply system; 2. a capillary system; 3. a glass slide; 4. a PDMS sheet; 5. a dispersed phase outlet; 6. a first dispersed phase inlet; 7. a second dispersed phase inlet; 8. inputting a capillary tube; 9. an auxiliary capillary tube; 10. a connecting member; 11. an output capillary; 12. an upper port; 13. a lower port; 14. a horizontal port; 15. an airflow controller; 16. a gas cylinder; 17. a first dispersed phase flow path; 18. a second dispersed phase flow path; 19. an airflow path.
In the drawings, like parts are provided with like reference numerals. The drawings are not to scale.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Fig. 1 is a schematic view of a microfluidic device according to the present invention, as shown in fig. 1, the microfluidic device includes:
the micro-fluidic chip glue supply system 1 is used for inputting dispersed phase solution;
and the capillary jetting system 2 is used for inputting the dispersed phase solution output by the micro-fluidic chip glue supply system 1, and introducing gas to cut the dispersed phase solution to form hydrogel particles with a multi-compartment structure.
The microfluidic device described above is a microfluidic device for preparing gas-driven droplet cutting features of patterned hydrogel particles. The device can effectively prepare the patterned hydrogel particles, control the structural characteristics of the patterned hydrogel particles, pneumatically drive the cutting of liquid drops to be green and safe, and is suitable for the field of cell culture. The micro-fluidic chip glue supply system can be used as a three-dimensional glue supply system to flexibly and variably manufacture hydrogel particles with various structures.
In one embodiment, the microfluidic chip glue supply system 1 includes a glass slide 3, a PDMS sheet 4, and a microfluidic chip, where the microfluidic chip (not shown) is placed on the glass slide 3, the microfluidic chip is provided with a dispersed phase inlet and a dispersed phase outlet 5, the microfluidic chip inputs a dispersed phase solution to form a laminar flow structure, and the PDMS sheet 4 is located on the glass slide 3 and surrounds the microfluidic chip to serve as a barrier for the dispersed phase solution.
Optionally, the dispersed phase outlet is perpendicular to the microfluidic chip.
In one embodiment, the capillary spray system 2 includes an input capillary 8, an output capillary 11 and a connecting member 10, the input capillary 8 is communicated with the dispersed phase outlet 5, the dispersed phase solution in a laminar structure flows into the input capillary 8 through the dispersed phase outlet 5, one end of the connecting member 10 is connected with the input capillary 8, the other end of the connecting member is connected with the output capillary 11, the input capillary 8 and the output capillary 11 are coaxial, the connecting member 10 is provided with a gas inlet, and the dispersed phase solution flowing out of the input capillary 8 is cut by gas to form hydrogel particles in a multi-compartment structure.
Optionally, the connection 10 is a three-way valve.
Optionally, the microfluidic chip is coaxially connected with the horizontal axis of the input capillary 8 to form a dispersed phase microchannel, and the vertical axes of the input capillary 8 and the output capillary 11 are coaxial. The microfluidic device is a pneumatically driven microfluidic device for preparing patterned hydrogel particles and has a horizontal microfluidic chip, a vertical capillary jetting system 2 and a gas-driven droplet cutting feature.
Optionally, the capillary tube spraying system 2 further comprises an auxiliary capillary tube 9, an outer wall of the auxiliary capillary tube 9 is in clearance fit with a connecting piece 10, an inner wall of the auxiliary capillary tube 9 is in clearance fit with the input capillary tube 8, the connecting piece 10 is in clearance fit with the output capillary tube 11, and vertical axes of the input capillary tube 8 and the output capillary tube 11 are coaxial through the connecting piece 10 and the auxiliary capillary tube 9. That is, the dispersed phase outlet 5 of the microfluidic chip, the input capillary 8, the auxiliary capillary 9, the three-way valve (connecting piece 10) and the output capillary 11 are coaxially connected, and the three-way valve, the air flow controller 15 and the gas cylinder 16 are communicated and fixed at the connecting positions through hot melt adhesive.
Optionally, the capillary tube spraying system 2 further comprises an air flow controller 15 for controlling the flow rate of the cutting dispersion phase solution gas, and the control for adjusting the size of the hydrogel particles is realized by adjusting the pressure of the gas nozzle in the capillary tube spraying system 2.
In one embodimentAs shown in fig. 2, the input capillary 8 is coaxially inserted into the three-way valve (connecting piece 10) and the output capillary 11 under the auxiliary fixation of the auxiliary capillary 9, the external pressure gas is adjusted by the gas flow controller 15 to enter the horizontal port 14 of the three-way valve to cut the glue solution flowing out of the input capillary 8 into single drops, and the outer diameter d of the input capillary 8inputAnd the inner diameter d of the auxiliary capillary 9middleThe relationship of (1) is: dinput＝dmiddle-h, wherein h is 50-100 μm, the outer diameter d of the auxiliary capillary 9middle’And the inner diameter d of the upper port 12 of the three-way valveinnerA relationship of dmiddle’＝dinnerL, l is 100-outputD is the same as the inner diameter of the lower port 13 of the three-way valve (the inner diameters of the upper port 12 and the lower port 13 of the three-way valve are the same) dinnerA relationship of doutput＝dinnerR, r ═ 100-. The horizontal port 14 of the three-way valve communicates with the gas flow controller 15 and the gas cylinder 16 for the input of a continuous gas fluid.
In one embodiment, the microfluidic device comprises a plurality of microfluidic chips and a plurality of input capillaries 8, which form a multi-dispersed phase microchannel, and controls the input of multi-dispersed phase solution and the internal structure of the patterned hydrogel particles through different arrangements of the dispersed phase microchannels. That is, the micro-fluidic chip glue supply system 1 can flexibly design the micro-channel assembly mode of multiple dispersed phases, and the internal structure (number of chambers and material of the chambers) of the patterned hydrogel particles can be controlled by correspondingly controlling the input of the multiple dispersed phases only by adjusting the arrangement and design of the micro-channels on the micro-fluidic chip. The pressure airflow driving source in the capillary jetting system 2 provides pressure airflow to complete droplet cutting, is green and safe, and is suitable for 3D cell culture applied to the field of biomedicine. Patterned hydrogel microparticles having a heterostructure are manufactured by using a preset chip pattern.
In one embodiment, the microfluidic device comprises a microfluidic chip glue supply system 1 and a capillary spray system 2; the microfluidic chip glue supply system 1 comprises a glass slide 3 and a PDMS sheet 4; the capillary injection system 2 comprises an input capillary 8, an auxiliary capillary 9, a three-way valve (a connecting piece 10), an output capillary 11, an air flow controller 15 and a gas steel cylinder 16; the microfluidic chip glue supply system 1 positioned at the upstream is communicated with the capillary injection system 2 through an input capillary 8 in the capillary injection system 2 positioned at the downstream; an input capillary 8 and an output capillary 11 are respectively inserted from an upper port 12 and a lower port 13 of a three-way valve, the input capillary 8 is coaxially inserted into the output capillary 11 under the assistance of an auxiliary capillary 9, airflow provided by a gas steel cylinder 16 is regulated and controlled by an airflow controller 15 and is injected into the three-way valve through a horizontal port 14 of the three-way valve, and the airflow and dispersed phase solution are cut in the output capillary 11 to prepare the patterned hydrogel particles. The invention provides a three-dimensional integrated microfluidic device consisting of a horizontal microfluidic chip and a vertical capillary system, which replaces the traditional hydrogel particle preparation technology, and the pneumatic drive is used as a power source to finish the cutting preparation of liquid drops. The design of the microfluidic chip is simply changed, the regulation and control of the internal structure of the patterned hydrogel particles are conveniently and efficiently realized, the limitation of commercial device materials is avoided, and the green and safe gas driving equipment provides cell culture conditions with higher biocompatibility for the application of high-order patterned hydrogel particles in the field of biomedicine.
In one embodiment, the input capillary 8 is coaxially connected with the disperse phase outlet 5 of the upstream microfluidic chip to form a disperse phase microchannel; the output capillary 11 is coaxially inserted into the lower port 13 of the three-way valve to jointly form a continuous phase microchannel, and the upstream microfluidic chip can flexibly design a microchannel assembly mode of multiple disperse phases, such as a PDMS sheet 4 with adjustable microchannel design, a disperse phase outlet 5 and a disperse phase inlet; the coaxial downstream capillary injection system 2 inputs disperse phase by using an input capillary 8, the outer diameter of the coaxial input capillary 8 is matched with the inner diameter of an auxiliary capillary 9, and the outer diameter of the auxiliary capillary 9 is matched with the inner diameter of an upper port 12 of a three-way valve, so that the auxiliary capillary 9 promotes the input capillary 8 to be coaxial with the three-way valve; the horizontal port 14 of the three-way valve is communicated with an air flow controller 15 and a gas steel cylinder 16, and continuous gas fluid is input to wrap the dispersed phase from 360 degrees; the outer diameter of the output capillary 11 is sized to match the inner diameter of the lower port 13 of the three-way valve to facilitate co-axial alignment so that the input capillary 8 is co-axial with the output capillary 11.
In one embodiment, as shown in fig. 3 and 5, the microfluidic chip has two dispersed phase input ports, and the microfluidic chip comprises a glass slide 3, a PDMS sheet 4, a dispersed phase outlet 5, a first dispersed phase inlet 6, and a second dispersed phase inlet 7, and is used for preparing the double-chamber hydrogel particles, and preferably, the two dispersed phase inlets are symmetrically arranged relative to the dispersed phase outlet and can form the same double-chamber
In one embodiment, as shown in fig. 6, the microfluidic chip has six dispersed phase inlets for making six-chamber hydrogel particles, which may be located on the six bisectors of the circle surrounding the dispersed phase outlet 5, resulting in the same six compartments as compared to an otherwise configured dispersed phase inlet.
The above embodiment shows an example of six chambers, but the present invention is not limited thereto, and more chambers such as three chambers, four chambers, five chambers, and seven chambers may be formed by a plurality of dispersed phase inlets.
In one embodiment, as shown in FIG. 7, one dispersed phase inlet and dispersed phase outlet 5 are positioned on the same line, and the other two dispersed phase inlets are symmetrically disposed with respect to the line to form an asymmetric three-chamber hydrogel particle.
In the above-described exemplary embodiments, the input capillary 8, the auxiliary capillary 9 and the output capillary 11 are each, optionally, a glass capillary.
The micro-fluidic device is assembled by integrating the micro-fluidic chip and the capillary injection system 2, and has simple structure, easily obtained materials and easy realization. The internal structure (the number of chambers and the material of the chambers) of the patterned hydrogel particles is controllable, and can be realized by correspondingly controlling the input of multiple dispersed phases only by adjusting the arrangement and design of microchannels on an upstream microfluidic chip, so that the method can be used for breaking through the preparation of more complex and higher-order patterned hydrogel particles. Meanwhile, the preparation of the patterned hydrogel particles is realized by gas cutting, so that the green safety performance of the preparation method is greatly improved.
The invention also provides a method for preparing patterned hydrogel particles by adopting the microfluidic device, which comprises the following steps:
injecting the dispersed phase solution into the micro-fluidic chip glue supply system 1;
the dispersed phase solution of the micro-fluidic chip glue supply system 1 enters a capillary spraying system 2;
and introducing gas into the capillary spraying system 2, and cutting the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
In one embodiment, the preparation method of the patterned hydrogel particles comprises the steps of injecting a dispersion phase solution into a microfluidic chip of a microfluidic chip glue supply system to form a laminar flow structure; the dispersed phase solution of the laminar flow structure of the microfluidic chip glue supply system enters a capillary tube injection system; and introducing gas into the capillary spraying system, and cutting the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
In one embodiment, the method of making a patterned hydrogel microparticle further comprises: and injecting the dispersed phase solution into the upstream micro-fluidic chip, entering the input capillary 8 through a dispersed phase outlet 5 of the micro-fluidic chip, entering the three-way valve, entering the output capillary 11, controlling the gas flow provided by the gas steel cylinder 16 through the gas flow controller 15, and injecting the gas flow and the dispersed phase solution into the three-way valve through the horizontal port 14 of the three-way valve, wherein the gas flow and the dispersed phase solution are cut in a gas cutting area of the output capillary 11, and the green and safe preparation process of the patterned hydrogel particles is completed.
In one embodiment, a method of making a patterned hydrogel microparticle includes:
preparing a dispersed phase solution, wherein the dispersed phase can be 1% sodium alginate aqueous solution aiming at a water/oil system;
respectively integrally assembling the upstream microfluidic chip adhesive supply systems 1 with different designs with the downstream capillary injection system 2, namely connecting the dispersed phase outlet 5 with the input capillary 8, and sealing the joint by using hot melt adhesive; inserting the output capillary tube 11 into the three-way valve to a certain depth through the lower port 13 of the three-way valve, inserting the input capillary tube 8 into the output capillary tube 11 to a certain depth from the inside of the auxiliary capillary tube 9 through the upper port 12 of the three-way valve, and sealing the joint by using hot melt adhesive; the horizontal port 14 of the three-way valve, the air flow controller 15 and the gas steel cylinder 16 are communicated, and the joint is sealed by hot melt adhesive to form an integral sealing structure, so that the device is built;
and respectively injecting the prepared dispersion solution into the corresponding dispersed phase inlet, and adjusting the flow of the dispersed phase and the airflow to realize the preparation of the patterned hydrogel microspheres.
In one embodiment, a method of making a patterned hydrogel microparticle includes:
an input capillary 8 is horizontally and coaxially connected with a disperse phase outlet 5 of the micro-fluidic chip to form a disperse phase micro-channel;
the outer diameter of the input capillary 8 is matched with the inner diameter of the auxiliary capillary 9, the outer diameter of the auxiliary capillary 9 is matched with the inner diameter of the upper port 12 of the three-way valve, and the auxiliary capillary 9 is inserted into the upper port 12 of the three-way valve;
coaxially inserting an output capillary tube 11 into a lower port 13 of a three-way valve to form a continuous phase micro-channel together, wherein an upper port 12 and a lower port 13 of the three-way valve are coaxial;
designing a microchannel assembly mode of multiple disperse phases of the upstream microfluidic chip, for example, designing an adjustable microchannel PDMS sheet 4, a disperse phase outlet 5 and a disperse phase inlet;
inputting a dispersed phase by utilizing a dispersed phase inlet, a dispersed phase outlet 5 and an input capillary 8;
the horizontal port 14 of the three-way valve is communicated with an air flow controller 15 and a gas steel cylinder 16, and continuous gas fluid is input to realize the wrapping and cutting of dispersed phases from 360 degrees, so that hydrogel particles with a multi-compartment structure corresponding to the assembly mode of the microchannel are formed.
In one embodiment, as shown in fig. 4, taking the preparation of the double-chamber hydrogel particles as an example, the two-phase dispersed phase aqueous solution flows along the first dispersed phase flow path 17, the second dispersed phase flow path 18 enters the upstream microfluidic chip gel supply system 1 through the first dispersed phase inlet 6 and the second dispersed phase inlet 7, converged at a dispersed phase outlet 5 of the microfluidic chip, flows into an input capillary 8 connected with the dispersed phase outlet 5 of the microfluidic chip in a laminar flow mode, and enters an output capillary in a laminar flow state, at the moment, an airflow controller 15 and a gas steel cylinder 16 provide an airflow flow path 19 with adjustable pressure to be injected into the three-way valve through a horizontal port 14 of the three-way valve along the airflow flow path, then enters an output capillary 11, and then the airflow and the dispersed phase solution are cut in a gas cutting area of the output capillary 11 to prepare the double-cavity hydrogel particles.
In one embodiment, as shown in fig. 5, two different phases of dispersed phase solution a and dispersed phase solution b are injected into the microfluidic chip glue supply system 1, and are converged at the dispersed phase outlet 5 of the microfluidic chip, and flow into the input capillary 8 coaxially connected with the dispersed phase outlet 5 of the microfluidic chip in a laminar flow manner, and enter the interior of the three-way valve in a laminar flow state, and then are injected into the output capillary 11, and at this time, the gas flow provided by the gas cylinder 16 is regulated and controlled by the gas flow controller 15 and injected into the interior of the three-way valve through the horizontal port 14 of the three-way valve, and then is injected into the output capillary 11, and then the gas flow and the dispersed phase solution are cut in the. Due to the laminar flow effect in the micro-scale space, the internal structure of the prepared double-cavity hydrogel particle is that two compartments with equal volume and size are distributed around the central axis of the microsphere.
In an embodiment, fig. 6 shows a six-chamber hydrogel particle preparation example 2, in which six different dispersed phase solutions a, b, c, d, e, and f are injected into a microfluidic chip glue supply system 1, and are converged at a dispersed phase outlet 5 of the microfluidic chip, and flow into an input capillary 8 coaxially connected to the dispersed phase outlet 5 of the microfluidic chip in a laminar flow manner, and enter a three-way valve while maintaining a laminar flow state, and then are injected into an output capillary 11, and at this time, an air flow provided by a gas cylinder 16 is controlled by an air flow controller 15 and is injected into the output capillary 11 through a horizontal port 14 of the three-way valve, and then the air flow and the dispersed phase solution are cut in a gas cutting area of the output capillary 11, so as to prepare a six-chamber hydrogel particle. Due to the laminar flow effect in the micro-scale space, the internal structure of the prepared six-cavity hydrogel particle is formed by arranging six compartments with equal volume around the central axis of the microsphere.
In an embodiment, fig. 7 shows an asymmetric three-chamber hydrogel particle preparation example 3, three phases of different dispersed phase solutions a, b, and c are injected into a microfluidic chip glue supply system 1, and are converged at a dispersed phase outlet 5 of the microfluidic chip, and flow into an input capillary 8 coaxially connected to the dispersed phase outlet 5 of the microfluidic chip in a laminar flow manner, and enter an output capillary 11 after maintaining a laminar flow state, and then the gas flow provided by a gas cylinder 16 is injected into the output capillary 11 through a horizontal port 14 of a three-way valve under the control of a gas flow controller 15, and then the gas flow and the dispersed phase solution are cut in a gas cutting area of the output capillary 11, so as to prepare the three-chamber hydrogel particle. Due to the laminar flow effect in the micro-scale space, the internal structure of the prepared asymmetric three-chamber hydrogel particle is that three compartments with uneven volume and size are distributed around the central axis of the microsphere.
The patterned hydrogel particle preparation method and the microfluidic device realize wider manufacture of a liquid drop structure by adjusting the design of the microfluidic chip in the device; the control of adjusting the size of hydrogel particles is realized by adjusting the pressure of the gas nozzle, and the three-dimensional precise fluid control and green safety of the three-dimensional micro-droplet generating device can be applied to the fields of biological 3D culture in precise biomedicine and the like.
The present invention is capable of other embodiments, and various changes and modifications can be made by one skilled in the art without departing from the spirit and scope of the invention.
Claims (10)
1. A microfluidic device, comprising:
the micro-fluidic chip glue supply system comprises a micro-fluidic chip, wherein the micro-fluidic chip inputs a dispersed phase solution to form a laminar flow structure;
and the capillary jetting system is used for inputting the dispersed phase solution with the laminar structure, and introducing gas to cut the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
2. The microfluidic device according to claim 1, wherein the microfluidic chip glue supply system further comprises a glass slide and a PDMS sheet, the microfluidic chip is placed on the glass slide, the microfluidic chip is provided with a dispersed phase inlet and a dispersed phase outlet, the dispersed phase outlet is perpendicular to the microfluidic chip, and the PDMS sheet is located on the glass slide and surrounds the microfluidic chip to serve as a barrier for a dispersed phase solution.
3. The microfluidic device according to claim 2, wherein the capillary ejector system comprises an input capillary, an output capillary and a connecting member, the input capillary is communicated with the dispersed phase outlet, the dispersed phase solution flows into the input capillary through the dispersed phase outlet, one end of the connecting member is connected with the input capillary, the other end of the connecting member is connected with the output capillary, the input capillary and the output capillary are coaxial, the connecting member is provided with a gas inlet, and the dispersed phase solution flowing out of the input capillary is cut by gas to form hydrogel particles with a multi-compartment structure.
4. The microfluidic device according to claim 3, wherein the connector is a three-way valve.
5. The microfluidic device according to claim 3, wherein the microfluidic chip is coaxially connected to the input capillary transverse axis to form a dispersed phase microchannel, and the input capillary and the output capillary vertical axis are coaxial.
6. The microfluidic device according to claim 5, wherein the capillary ejector system further comprises an auxiliary capillary, wherein an outer wall of the auxiliary capillary is in clearance fit with the connector, an inner wall of the auxiliary capillary is in clearance fit with the input capillary, the connector is in clearance fit with the output capillary, and a vertical axis of the input capillary and a vertical axis of the output capillary are coaxial through the connector and the auxiliary capillary.
7. The microfluidic device according to claim 1, wherein the capillary jet system further comprises a gas flow controller for controlling a flow rate of the gas for cutting the dispersed phase solution.
8. The microfluidic device according to claim 5, comprising a plurality of microfluidic chips and a plurality of input capillaries, wherein the microchannels of multiple dispersed phases are formed, and the internal structure of the patterned hydrogel particles is controlled by controlling the input of multiple dispersed phase solutions through different arrangements of the microchannels of the dispersed phases.
9. The microfluidic device according to claim 2, wherein the microfluidic chip has two dispersed phase input ports symmetrically disposed with respect to the dispersed phase output port.
10. A method of making patterned hydrogel microparticles using the microfluidic device of any of claims 1-9, comprising:
injecting the dispersion phase solution into a micro-fluidic chip of a micro-fluidic chip glue supply system to form a laminar flow structure;
the dispersed phase solution of the laminar flow structure of the microfluidic chip glue supply system enters a capillary tube injection system;
and introducing gas into the capillary spraying system, and cutting the dispersed phase solution to form the hydrogel particles with the multi-compartment structure.
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Citations (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1816393A (en) * | 2003-05-21 | 2006-08-09 | 国家科学研究中心 | Micro-fluid apparatus |
| US20090286298A1 (en) * | 2008-05-13 | 2009-11-19 | Commissariat A L'energie Atomique | Microfluidic device, system, and method for controlled encapsulation of particles or particle clusters |
| CN102008983A (en) * | 2010-11-01 | 2011-04-13 | 武汉大学 | Microfluidic chip suitable for producing microcapsules |
| CN102490470A (en) * | 2011-12-07 | 2012-06-13 | 北京清科奥博仪器设备有限公司 | Method and device for controlling tiny droplet spraying by airflows |
| CN102580799A (en) * | 2012-02-29 | 2012-07-18 | 清华大学 | Machining method of micro-drop and micro-fluidic control chip |
| CN103721655A (en) * | 2014-01-06 | 2014-04-16 | 武汉理工大学 | Preparation method of chitosan microcapsule with uniform size and controllable size |
| CN103861535A (en) * | 2014-03-19 | 2014-06-18 | 中国科学技术大学 | Single-dispersity and opposite-polarity Janus gel microsphere with core-shell structure, preparation method and microfluid control device used |
| WO2015066115A1 (en) * | 2013-10-29 | 2015-05-07 | President And Fellows Of Harvard College | Drying techniques for microfluidic and other systems |
| CN104645903A (en) * | 2013-11-15 | 2015-05-27 | 北京慧荣和科技有限公司 | Aerosol generating device |
| US20150352513A1 (en) * | 2006-02-07 | 2015-12-10 | Stokes Bio Limited | Microfluidic Droplet Queuing Network |
| WO2016078340A1 (en) * | 2014-11-17 | 2016-05-26 | 中国科学院微生物研究所 | Apparatus, system, and method for dispensing/mixing a small quantity of liquid |
| CN107109339A (en) * | 2014-10-29 | 2017-08-29 | 康宁股份有限公司 | Irrigate bioreactor platform |
| CN107930542A (en) * | 2017-11-13 | 2018-04-20 | 王华楠 | One-step method continuously prepares the microflow control technique of calcium alginate microgel |
| CN108525715A (en) * | 2018-05-23 | 2018-09-14 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and the method that microballoon is quantitatively wrapped up for drop |
| CN109908983A (en) * | 2019-04-18 | 2019-06-21 | 哈尔滨工业大学 | A kind of micro-fluidic chip for microlayer model high proportion split extraction with three-dimensional pyramidal structure |
| US20190224670A1 (en) * | 2017-12-25 | 2019-07-25 | Revotek Co., Ltd | Microfluidic chip and control method thereof, droplet generation device, and microsphere preparation device |
| US20200171456A1 (en) * | 2017-08-15 | 2020-06-04 | University Of Maryland, College Park | Multicompartment Capsules and Methods and Systems for Forming Same |
| CN111701627A (en) * | 2020-06-20 | 2020-09-25 | 西安交通大学 | Core-shell liquid drop rapid generation device and method based on surface acoustic wave micro-fluidic |
| WO2020208553A1 (en) * | 2019-04-08 | 2020-10-15 | Association For The Advancement Of Tissue Engineering And Cell Based Technologies & Therapies (A4Tec) - Associação | Method for distribution of active factors in an artificial tissue, products and uses thereof |
| CN111905845A (en) * | 2020-06-17 | 2020-11-10 | 西安交通大学 | Multi-particle-size high-speed liquid drop generating device based on airflow acceleration |
| CN112275336A (en) * | 2020-10-20 | 2021-01-29 | 大连理工大学 | Multi-channel integrated micro-fluidic chip and method for preparing monodisperse gel microspheres by using same in high throughput |
| CN112300940A (en) * | 2020-10-30 | 2021-02-02 | 大连医科大学 | Periodontal soft tissue bionic chip constructed based on microfluidic technology and application thereof |
-
2021
- 2021-03-01 CN CN202110226754.9A patent/CN113070108B/en active Active
Patent Citations (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1816393A (en) * | 2003-05-21 | 2006-08-09 | 国家科学研究中心 | Micro-fluid apparatus |
| US20150352513A1 (en) * | 2006-02-07 | 2015-12-10 | Stokes Bio Limited | Microfluidic Droplet Queuing Network |
| US20090286298A1 (en) * | 2008-05-13 | 2009-11-19 | Commissariat A L'energie Atomique | Microfluidic device, system, and method for controlled encapsulation of particles or particle clusters |
| CN102008983A (en) * | 2010-11-01 | 2011-04-13 | 武汉大学 | Microfluidic chip suitable for producing microcapsules |
| CN102490470A (en) * | 2011-12-07 | 2012-06-13 | 北京清科奥博仪器设备有限公司 | Method and device for controlling tiny droplet spraying by airflows |
| CN102580799A (en) * | 2012-02-29 | 2012-07-18 | 清华大学 | Machining method of micro-drop and micro-fluidic control chip |
| WO2015066115A1 (en) * | 2013-10-29 | 2015-05-07 | President And Fellows Of Harvard College | Drying techniques for microfluidic and other systems |
| CN104645903A (en) * | 2013-11-15 | 2015-05-27 | 北京慧荣和科技有限公司 | Aerosol generating device |
| CN103721655A (en) * | 2014-01-06 | 2014-04-16 | 武汉理工大学 | Preparation method of chitosan microcapsule with uniform size and controllable size |
| CN103861535A (en) * | 2014-03-19 | 2014-06-18 | 中国科学技术大学 | Single-dispersity and opposite-polarity Janus gel microsphere with core-shell structure, preparation method and microfluid control device used |
| CN107109339A (en) * | 2014-10-29 | 2017-08-29 | 康宁股份有限公司 | Irrigate bioreactor platform |
| WO2016078340A1 (en) * | 2014-11-17 | 2016-05-26 | 中国科学院微生物研究所 | Apparatus, system, and method for dispensing/mixing a small quantity of liquid |
| US20200171456A1 (en) * | 2017-08-15 | 2020-06-04 | University Of Maryland, College Park | Multicompartment Capsules and Methods and Systems for Forming Same |
| CN107930542A (en) * | 2017-11-13 | 2018-04-20 | 王华楠 | One-step method continuously prepares the microflow control technique of calcium alginate microgel |
| US20190224670A1 (en) * | 2017-12-25 | 2019-07-25 | Revotek Co., Ltd | Microfluidic chip and control method thereof, droplet generation device, and microsphere preparation device |
| CN108525715A (en) * | 2018-05-23 | 2018-09-14 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and the method that microballoon is quantitatively wrapped up for drop |
| WO2020208553A1 (en) * | 2019-04-08 | 2020-10-15 | Association For The Advancement Of Tissue Engineering And Cell Based Technologies & Therapies (A4Tec) - Associação | Method for distribution of active factors in an artificial tissue, products and uses thereof |
| CN109908983A (en) * | 2019-04-18 | 2019-06-21 | 哈尔滨工业大学 | A kind of micro-fluidic chip for microlayer model high proportion split extraction with three-dimensional pyramidal structure |
| CN111905845A (en) * | 2020-06-17 | 2020-11-10 | 西安交通大学 | Multi-particle-size high-speed liquid drop generating device based on airflow acceleration |
| CN111701627A (en) * | 2020-06-20 | 2020-09-25 | 西安交通大学 | Core-shell liquid drop rapid generation device and method based on surface acoustic wave micro-fluidic |
| CN112275336A (en) * | 2020-10-20 | 2021-01-29 | 大连理工大学 | Multi-channel integrated micro-fluidic chip and method for preparing monodisperse gel microspheres by using same in high throughput |
| CN112300940A (en) * | 2020-10-30 | 2021-02-02 | 大连医科大学 | Periodontal soft tissue bionic chip constructed based on microfluidic technology and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 嵇庆磊: "一种基于液滴控制的微流体处理器", 《中国优秀博硕士学位论文全文数据库(硕士) 信息科技辑》 * |
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