CN117483022A - High-viscosity micro-droplet generation device and method based on three-dimensional micro-channel structure - Google Patents

High-viscosity micro-droplet generation device and method based on three-dimensional micro-channel structure Download PDF

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Publication number
CN117483022A
CN117483022A CN202311511172.0A CN202311511172A CN117483022A CN 117483022 A CN117483022 A CN 117483022A CN 202311511172 A CN202311511172 A CN 202311511172A CN 117483022 A CN117483022 A CN 117483022A
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channel
micro
viscosity
straight
droplet
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张家铭
程熠敏
李彬
刘召越
皮俊杰
张雯馨
陈海航
李泽文
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Nanjing Avionics Intelligent Manufacturing Technology Co ltd
Nanjing University of Aeronautics and Astronautics
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Nanjing Avionics Intelligent Manufacturing Technology Co ltd
Nanjing University of Aeronautics and Astronautics
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Priority to CN202311511172.0A priority Critical patent/CN117483022A/en
Publication of CN117483022A publication Critical patent/CN117483022A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/0241Drop counters; Drop formers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

The present disclosure provides a device and a method for generating high-viscosity micro-droplets based on a three-dimensional micro-channel structure, wherein the three-dimensional micro-channel structure is T-shaped and comprises a first straight channel, a vertical channel, a second straight channel and a third straight channel which are sequentially communicated; a group of boss structures are symmetrically arranged in the second straight channel near the inner walls of the two sides of the main channel, and the outer end surfaces of the microtubes can be abutted against the outer end surfaces of the boss structures after the microtubes extend into the vertical channel, so that a high-viscosity micro-droplet generating channel is formed between the two boss structures; a conical channel is formed at the joint of the high-viscosity micro-droplet generation channel and the third straight channel, and the high-viscosity micro-droplet is stably output from the third straight channel through the conical channel; the invention designs a brand-new tip mode, realizes high monodispersity and uniformity of the high-viscosity micro-droplets, has controllable size, improves the stability of the generation of the high-viscosity micro-droplets, can be repeatedly used based on a detachable design through a three-dimensional micro-channel structure, and expands the application range of the technology.

Description

High-viscosity micro-droplet generation device and method based on three-dimensional micro-channel structure
Technical Field
The disclosure relates to the technical field of microfluidics, in particular to a high-viscosity micro-droplet generation device and method based on a three-dimensional micro-channel structure.
Background
The general size of the micro-droplets is below 100 mu m, and the method is widely applied to various fields such as drug research and development, material synthesis, chemical reaction and the like, and the controllable micro-droplet generation method with high monodispersity is particularly important. The droplet microfluidic technology is widely used because of its ability to controllably produce droplets of uniform size.
In recent years, microscale manipulation of high-viscosity fluids such as functional polymer solutions and biological hydrogels has become an important issue in the industry, but a method for stably and controllably generating high-viscosity micro-droplets has been recently reported, and the following problems still exist in the high-viscosity micro-droplet generation technology at present: 1. the traditional jet mode generally adopts a structure of a micro injection pump and a nozzle to control the jet quantity of liquid and the flow of high-viscosity liquid, various phenomena such as stretching, crushing, atomizing and the like exist in the jet process of the high-viscosity liquid, the viscosity and the jet pressure of the liquid are found to have obvious influence on the jet form of the liquid through careful observation and analysis of the jet process, when the viscosity of a disperse phase is higher than 100mPa-s, the jetted liquid drops are easier to deform and crush, the non-uniformity of the size of the liquid drops is increased, and the technology is difficult to stably generate high-viscosity micro liquid drops with controllable and uniform size; 2. the high-viscosity liquid drops can be prepared by diluting the high-viscosity solution or directly utilizing the reaction between the two components, for example, the mixed solution of the high-viscosity sodium alginate and the calcium chloride is used as a dispersion phase to be communicated with a microfluidic chip, but the mixed solution is difficult to shear to form the liquid drops, the stability is poor, and meanwhile, the method can change the fluid properties so as to influence the functions of the liquid drops; 3. the droplet inversion technology effectively improves the uniformity of droplets, but the droplet size is difficult to control accurately, and the change of the regional property of a micro-channel greatly improves the processing difficulty of the device, so that the device is difficult to be used as a high-viscosity droplet generation device for mass production; 4. the external surface acoustic wave is used as an external force field, and the external surface acoustic wave is combined with the microfluidic liquid drop generating chip to induce uniform and stable generation of high-mucus drops, and because the generating device of the surface acoustic wave consists of a piezoelectric substrate and an interdigital transducer processed on the upper surface, in order to realize effective combination of the surface acoustic wave and microfluid, the microfluidic chip is generally directly bonded on the upper part of the piezoelectric substrate, the complexity of a system is increased, the bonding is irreversible, and when the microfluidic chip is blocked, damaged and other problems occur, the piezoelectric substrate cannot be recovered and can only be scrapped together with the chip, so that the recycling rate of the device is reduced, and the processing cost of the high-viscosity generating device produced in batches by the method is greatly increased. Therefore, there is an urgent need for a device and a method for generating high-viscosity micro-droplets based on a three-dimensional micro-channel structure to solve the above problems.
Disclosure of Invention
Aiming at the problems of uncontrollable size, low stability, poor uniformity and the like of the high-viscosity micro-droplet generated by the high-viscosity droplet generation technology, the invention designs a full-scale high-viscosity micro-droplet generation device and method based on a three-dimensional micro-channel structure, which aim to realize controllable and stable generation of the high-viscosity micro-droplet without increasing the complexity of a device/a micro-fluidic chip and changing the flow rate and the property of fluid.
In order to solve the problems, the invention provides the following technical scheme: the first aspect of the present disclosure provides a high-viscosity micro-droplet generating device based on a three-dimensional micro-channel structure, which comprises a micro-tube and a micro-fluidic chip, wherein the three-dimensional micro-channel structure arranged inside the micro-fluidic chip is of a T-shaped structure, and the micro-channel structure comprises a continuous phase module, wherein a first straight channel of the T-shaped structure is formed inside the continuous phase module and is used for inputting continuous phase solution; the dispersion phase module is internally provided with a vertical channel with the T-shaped structure and is used for extending a micro pipe into the dispersion phase module, and a high-viscosity dispersion phase solution is input through the micro pipe; the high-viscosity micro-droplet module is internally provided with a second straight channel with the T-shaped structure and is used for generating high-viscosity micro-droplets; the outlet module is internally provided with a third straight channel with the T-shaped structure and is used for outputting high-viscosity micro liquid drops; the first straight channel, the second straight channel and the third straight channel are sequentially connected and communicated to form a main channel of the microfluidic chip, and central axes of the channels are coincident; a group of boss structures are symmetrically arranged in the second straight channel near the inner walls of the two sides of the main channel, the outer end faces of the microtubes extend into the vertical channel and can be abutted against the outer end faces of the boss structures, so that a high-viscosity micro-droplet generation channel is formed between the two boss structures, and the high-viscosity micro-droplet generation channel is in a regular prismatic table shape; and a conical channel for stably conveying the high-viscosity micro-droplets is formed at the joint of the high-viscosity micro-droplet generation channel and the third straight channel, and the high-viscosity micro-droplets are output from the third straight channel through the conical channel.
Further, the high viscosity dispersed phase solution refers to a fluid having a minimum viscosity of not less than 100 mPa-s.
Further, the horizontal width of the channel at the joint of the high-viscosity micro-droplet generation channel and the third straight channel is equal, the cross section sizes of the high-viscosity micro-droplet generation channel and the conical channel which are oppositely arranged are gradually increased along the opposite direction of the joint, the longitudinal inner diameter of the conical channel is in gradient-like change, and finally the outer sections of the high-viscosity micro-droplet generation channel and the conical channel are in sealing connection with the inner side wall of the main channel.
Further, the vertical channel penetrates through the outer part of the second straight channel and does not completely penetrate through the second straight channel, so that a group of limiting structures are symmetrically formed on two sides of the main channel, and a certain distance is kept between the outer end face of the limiting structure and the outer end face of the main channel.
Further, the first straight channel, the vertical channel, the high-viscosity micro-droplet generation channel, the conical channel and the third straight channel are all integrally formed and prepared by a three-dimensional light-curing forming method of a 3D printing technology, and the preparation material of the three-dimensional light-curing forming method is photosensitive resin.
Further, the longitudinal inner diameter of the first straight channel is larger than the longitudinal inner diameter of the tapered channel, the longitudinal inner diameter of the tapered channel is larger than the longitudinal inner diameter of the high-viscosity micro-droplet generation channel, and the longitudinal inner diameters of the first straight channel and the third straight channel are equal.
Further, the cross sections of the first straight channel, the vertical channel and the third straight channel are round or rectangular, the inner diameters of the first straight channel and the third straight channel are 300-800 μm, the inner diameter of the vertical channel is 800-1600 μm, the height of the boss structure is 50-300 μm, the inner diameter of the micro tube is 50-800 μm, and the outer diameter of the micro tube is 300-1600 μm.
Further, the microtubes are detachably connected with the vertical channels.
A second aspect of the present disclosure provides a method of high viscosity micro droplet generation based on a three-dimensional microchannel structure, the method comprising: inserting a microtube into the bottom of a vertical channel, inputting a continuous phase solution into a first straight channel, inputting a high-viscosity dispersed phase solution into an inner diameter opening of the microtube in the vertical channel, and when the continuous phase solution flows through the high-viscosity micro-droplet generation channel, partially pouring the continuous phase solution into the inner diameter opening of the microtube at a junction to cause the high-viscosity dispersed phase solution to incompletely wet a pipe orifice so as to squeeze the high-viscosity dispersed phase solution at the junction, thereby generating high-viscosity micro-droplets with smaller area than the junction;
stably outputting the high-viscosity micro-droplets from the third straight channel through the conical channel;
the size of the generated high-viscosity micro-droplet can be further controlled by changing the size of the micro-tube or adjusting the gap distance of the micro-tube inserted into the vertical channel.
Compared with the prior art, the method has the following advantages:
(1) The high-viscosity micro-droplet generating device comprises a three-dimensional micro-channel structure, and compared with a traditional micro-fluidic device which is complex and expensive to prepare, the device uses a 3D printing micro-fluidic chip and commercial pipes to form a detachable three-dimensional micro-channel structure, and the device is simple to prepare, low in cost and easy to operate;
(2) The three-dimensional micro-channel structure provided by the disclosure realizes quick plugging and flexible disassembly of a micro-tube and a vertical channel based on a detachable design, is convenient to disassemble, clean and replace parts, can disassemble the micro-tube to solve the chip failure, so that the device can be repeatedly used, is convenient to assemble and use and maintain in a later period, is easy to obtain commercial micro-tubes and chip modules, can realize quick manufacture of the high-mucus-droplet micro-fluidic device, and has low overall cost;
(3) Compared with the two-dimensional micro-channel structure of the traditional micro-fluidic device, the novel three-dimensional micro-channel structure is provided, and under the combined action of the high-viscosity micro-droplet generation channel and the conical channel, the high-viscosity dispersed phase solution can stably stay at the junction in a smaller area, so that the generation size of the high-viscosity micro-droplet is greatly reduced, and the high-viscosity micro-droplet is stably output; the size of the high-viscosity micro-droplet is further controlled by changing the size of the micro-tube or adjusting the gap distance of the micro-tube inserted into the vertical channel, so that the generation range of the high-viscosity micro-droplet is greatly widened, and the controllable and stable generation of the high-viscosity micro-droplet can be realized under the condition that the complexity of a device/a micro-fluidic chip is not increased and the flow speed and the property of fluid are not changed, so that the high-viscosity micro-droplet has extremely high commercial application value;
(4) Based on the device, the high-viscosity micro-droplet generation method provided by the disclosure effectively inhibits the generation of jet flow mode (Jetting), generates a brand-new Tip mode (Tip), realizes high monodispersity and uniformity of high-viscosity micro-droplets, has controllable size, improves the stability of high-viscosity micro-droplet generation, and expands the application range of the technology.
Drawings
For a more complete understanding of the present disclosure and the advantages thereof, reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which:
FIG. 1 schematically illustrates a top view of a three-dimensional microchannel structure in accordance with an embodiment of the disclosure;
FIG. 2 schematically illustrates a cross-sectional view of a three-dimensional microchannel structure in accordance with an embodiment of the disclosure;
FIG. 3 schematically illustrates a three-dimensional schematic of a three-dimensional microchannel structure in accordance with an embodiment of the disclosure;
FIG. 4 schematically illustrates a flow chart of a method of generating highly viscous micro-droplets based on a three-dimensional microchannel structure in accordance with an embodiment of the disclosure;
FIG. 5 schematically illustrates an optical micrograph of the generation of highly viscous micro-droplets by the structure of a 3D printing micro-channel of an embodiment of the present disclosure;
fig. 6 schematically shows a schematic diagram of droplet comparisons for three different modes.
The reference numerals in the drawings are: 100. a three-dimensional microchannel structure; 10. a continuous phase module; 101. a first straight channel; 102. a continuous phase solution; 20. a dispersed phase module; 201. a vertical channel; 202. a microtube; 203. a junction; 204. a highly viscous dispersed phase solution; 205. a limit structure; 30. A high viscosity micro-droplet module; 301. a second straight channel; 302. a boss structure; 303. a high viscosity micro droplet generation channel; 304. high viscosity microdroplets; 40. an outlet module; 401. a third straight channel; 402. a tapered channel; 50. and a high viscosity dispersed phase solution outlet.
Detailed Description
Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. It should be understood that the description is only exemplary and is not intended to limit the scope of the present disclosure. In the following detailed description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It may be evident, however, that one or more embodiments may be practiced without these specific details. In addition, in the following description, descriptions of well-known structures and techniques are omitted so as not to unnecessarily obscure the concepts of the present disclosure.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. The terms "comprises," "comprising," and/or the like, as used herein, specify the presence of stated features, steps, operations, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, or components.
All terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art unless otherwise defined. It should be noted that the terms used herein should be construed to have meanings consistent with the context of the present specification and should not be construed in an idealized or overly formal manner.
Referring to fig. 1-6, the present invention provides a device and a method for generating high-viscosity micro-droplets based on a three-dimensional micro-channel structure, which generate a brand new Tip mode (Tip), realize high monodispersity and uniformity of the high-viscosity micro-droplets 304, have controllable size, improve the stability of generating the high-viscosity micro-droplets 304, and can be repeatedly used based on a detachable design through the three-dimensional micro-channel structure, wherein the device has the advantages of simple preparation, low cost and easy operation, and enlarges the application range of the technology.
A top view of a three-dimensional microchannel structure 100 according to an embodiment of the disclosure is schematically illustrated in fig. 1; and schematically illustrates a cross-sectional view of a three-dimensional microchannel structure 100 according to an embodiment of the disclosure, as in fig. 2.
As shown in fig. 1, the three-dimensional micro-channel structure 100 has a T-shaped structure, and specifically includes:
a continuous phase module 10, in which a first straight channel 101 of the T-shaped structure is formed for inputting a continuous phase solution 102;
a disperse phase module 20, in which a vertical channel 201 of the T-shaped structure is formed for the penetration of a micro tube 202, through which micro tube 202 a highly viscous disperse phase solution 204 is inputted;
specifically, the vertical channel 201 penetrates the outside of the second straight channel 301 and does not completely penetrate the outside, so that a group of limiting structures 205 are symmetrically formed on two sides of the main channel, and a certain distance is kept between the outer end surface of the limiting structure 205 and the outer end surface of the main channel; a vertical channel 201 with a certain thickness is formed in the microfluidic chip, a high-viscosity micro-droplet generation channel 303 can be positioned above or below the vertical channel 201 and is communicated with the high-viscosity dispersed phase outlet 50 to form a junction 203, at the junction 203, part of continuous phase solution 102 is partially poured into an inner diameter opening of a micro tube 202 at the junction 203, so that the high-viscosity dispersed phase solution 204 does not completely wet a nozzle, and the high-viscosity dispersed phase solution 204 at the junction 203 is extruded to form high-viscosity micro-droplets 304; the size of the generated high-viscosity micro-droplet is controlled by adjusting the gap distance between the micro-tube 202 and the limiting structure 205 inserted into the vertical channel 201, when the micro-tube 202 stretches into the outer end face of the limiting structure 205, the gap between the outer end face of the micro-tube 202 and the inner end face of the second straight channel 301 is the smallest, namely the high-viscosity micro-droplet generating channel 303 reaches the narrowest state, under the premise that the micro-tube 202 is not replaced, when the continuous phase solution 102 flows through the high-viscosity micro-droplet generating channel 303 in the narrowest state, the generated high-viscosity micro-droplet 304 is the smallest, when the micro-tube 202 stretches into the conical channel 402 at the joint to be the same in height, the gap between the outer end face of the micro-tube 202 and the inner end face of the second straight channel 301 is the largest, namely the high-viscosity micro-droplet generating channel 303 reaches the widest state, and when the continuous phase solution 102 flows through the high-viscosity micro-droplet generating channel 303 in the widest state, the generated high-viscosity micro-droplet 304 is the largest; therefore, the limit structure 205 is designed to better regulate the size of the high-viscosity micro-droplet 304 generated without changing the size of the micro-tube 202, so as to meet different practical application requirements;
a high-viscosity micro-droplet module 30, as shown in fig. 3, in which a second straight channel 301 with a T-shaped structure is formed for generating high-viscosity micro-droplets;
specifically, as shown in fig. 3, a set of boss structures 302 are symmetrically disposed in the second straight channel 301 near the inner walls of the two sides of the main channel, and the outer end surface of the micro tube 202 after extending into the vertical channel 201 may abut against the outer end surface of the boss structures 302, so that a high-viscosity micro droplet generating channel 303 is formed between the two boss structures 302, and the high-viscosity micro droplet generating channel 303 is in a regular prismatic table shape; specifically, the cross-sectional dimension of the high-viscosity micro-droplet generation channel 303 gradually decreases from the upstream to the downstream, and the high-viscosity micro-droplet generation channel 303 is used for transporting the continuous phase solution 102, and the continuous phase solution 102 generates more shearing force in the high-viscosity micro-droplet generation channel 303, so as to change the state of the continuous phase solution 102; the vertical passage 201 is used for inputting a high viscosity dispersed phase solution 204, and the high viscosity dispersed phase solution 204 refers to a high viscosity fluid having a minimum viscosity of not less than 100 mPa-s.
And an outlet module 40, in which a third straight channel 401 of the T-shaped structure is formed, for outputting high-viscosity micro droplets 304;
specifically, as shown in fig. 1-3, a conical channel 402 for stably conveying the high-viscosity micro-droplets is further formed at the connection part of the high-viscosity micro-droplet generation channel 303 and the third straight channel 401, and the high-viscosity micro-droplets 304 are output from the third straight channel 401 through the conical channel 402; the horizontal width of the channels at the joint is equal, the cross section sizes of the oppositely arranged high-viscosity micro-droplet generation channel 303 and the conical channel 402 are gradually increased along the opposite direction of the joint, the longitudinal inner diameter of the conical channel 402 is in gradient-like change, and finally the outer sections of the high-viscosity micro-droplet generation channel 303 and the conical channel 402 are respectively in sealing connection with the inner side wall of the main channel; as shown in FIG. 1, the lateral inner diameter of the junction of the tapered channel 402 and the high viscosity micro-droplet generation channel 303w 1 Equal, as shown in fig. 1, the lateral inner diameter of the high-viscosity micro-droplet generation channel 303 gradually decreases from left to right, the lateral inner diameter of the tapered channel 402 gradually increases, and the maximum lateral inner diameter of the high-viscosity micro-droplet generation channel 303 is equal to the maximum lateral inner diameter of the tapered channel 402.
The first straight channel 101, the second straight channel 301 and the third straight channel 401 are sequentially connected and communicated to form a main channel of the microfluidic chip, and central axes of the channels are coincident with each other as shown in fig. 1-2.
Specifically, as shown in fig. 3, a tapered channel 402 is provided inside the third straight channel 401, the upstream end of which communicates with the high-viscosity micro droplet generation channel 303, and the outer cross section of the other end of which is integrally formed with both inner side walls of the main channel and communicates with both inside. It should be noted that, the first straight channel 101, the vertical channel 201, the high-viscosity micro-droplet generating channel 303, the tapered channel 402, and the third straight channel 401 are all integrally formed by a stereolithography method using 3D printing technology, and the preparation materials are preferably photosensitive resins.
Specifically, as shown in FIG. 2, the lateral inner diameter of the first straight passage 101w 2 And the transverse inner diameter of the third straight passage 401w 3 Equal. The lateral length of the first straight channel 101 and the lateral length of the third straight channel 401 are not limited in the embodiments of the present disclosure, and are set according to practical application requirements.
In the embodiment of the disclosure, the longitudinal inner diameters of the first straight channel 101, the high-viscosity micro droplet generation channel 303 and the tapered channel 402 are all different, and the longitudinal inner diameters of the first straight channel 101 and the third straight channel 401 are the same, wherein the longitudinal inner diameter of the tapered channel 402 in the third straight channel 401 is in gradient change.
Specifically, as shown in FIGS. 1-2, due to the embedded arrangement of microtube 202 and high viscosity micro-droplet generation channel 303, the longitudinal inner diameter of first straight channel 101h 1 Greater than the longitudinal inner diameter of the tapered passage 402h 3 The longitudinal inner diameter of the tapered channel 402h 3 Is larger than the longitudinal inner diameter of the high-viscosity micro-droplet generation channel 303h 2 By combining the sequential reduction of the transverse inner diameter of the high-viscosity micro-droplet generation channel 303, more shearing force can be generated when the continuous phase solution 102 passes through the high-viscosity micro-droplet generation channel 303, so that the state of the continuous phase solution 102 can be changed more easily, the continuous phase solution 102 can stay at the junction 203 stably in a small area, and further part of the continuous phase solution 102 partially flows into the inner diameter opening of the micro tube 202 at the junction 203, so that the high-viscosity dispersed phase solution 204 does not completely wet the orifice, the high-viscosity dispersed phase solution 204 at the junction 203 is extruded, the effect of extruding the high-viscosity dispersed phase solution 204 is achieved, and the high-viscosity micro-droplet 304 with smaller area than the junction 203 is generated.
Specifically, as shown in fig. 1 and 3, the longitudinal inner diameter of the tapered passage 402 in the third straight passage 401h 3 And the gradient is like. It will be appreciated that as the transverse inner diameter of the tapered channel 402 becomes progressively larger, and the longitudinal inner diameterh 3 The longitudinal inner diameter of the conical channel 402 at the connection is larger than the longitudinal inner diameter of the high-viscosity micro-droplet generation channel 303, so that the generated high-viscosity micro-droplet 304 is more stably output in the inclined conical channel 402, and the high-viscosity micro-droplet 304 does not flow out of the gap between the conical channel 402 and the third straight channel 401 when the gap distance between the regulating microtube 202 and the limiting structure 205 is maximum during the adjustment of the gap distance when the regulating microtube 202 is inserted into the vertical channel 201, thereby ensuring the sealing circulation performance of the three-dimensional micro-channel structure 100;
in the embodiment of the present disclosure, to facilitate the integral formation of the entire structure, the longitudinal inner diameter of the first straight passage 101h 1 With the longitudinal inner diameter of the third straight channel 401h 4 Equal, i.e. the first straight channel 101 and the third straight channel 401 remain identical in size;
in the embodiment of the disclosure, the cross sections of the first straight channel 101, the vertical channel 201 and the third straight channel 401 are circular or rectangular, the inner diameters of the first straight channel 101 and the third straight channel 401 are between 300 μm and 800 μm, the inner diameter of the vertical channel 201 is between 800 μm and 1600 μm, the height of the boss structure 302 is between 50 μm and 300 μm, the inner diameter of the micro tube 202 is between 50 μm and 800 μm, the outer diameter thereof is between 300 μm and 1600 μm, and the specific size thereof is set according to practical application requirements. Specifically, as shown in fig. 5, in an embodiment of the present disclosure, the present method may produce highly viscous micro-droplets 304 of 100 μm and below based on the change of the three-dimensional micro-channel structure 100.
According to the embodiment of the disclosure, the microtube 202 is detachably connected with the vertical channel 201, so that the problem of failure resolution when channel congestion occurs in the microchannel can be solved through the detachable design, the device can be repeatedly used, and the use cost of the device is reduced.
Specifically, the three-dimensional micro-channel structure 100 uses a 3D printing micro-fluidic chip and a commercial pipe (micro-pipe 202) to form a detachable three-dimensional micro-channel structure 100, and the inner diameter of the commercial pipe (micro-pipe 202) can be selected to be matched with the size according to the requirement of preparing the size of the high-viscosity micro-droplet 304; compared with the traditional microfluidic structure which is complex and expensive to prepare, the microfluidic structure is simple to prepare, low in cost and easy to operate. The 3D printing material may be various types of photosensitive resins, preferably transparent photosensitive resins that match the 3D printer used.
It should be noted that, in the embodiment of the present disclosure, the structural dimensions of each component of the three-dimensional micro-channel structure 100 are not limited, for example, the opening angle formed by the longitudinal sections of the high-viscosity micro-droplet generating channel 303 and the tapered channel 402 may be between 0 ° and 90 °, preferably between 30 ° and 60 °, etc.; these are merely examples, which are not intended to limit the embodiments of the present disclosure.
Another aspect of the present disclosure provides a method of high viscosity micro-droplet generation based on a three-dimensional micro-channel structure 100, the method implemented with the three-dimensional micro-channel structure 100 as shown in fig. 1-3, the method comprising:
s501: inserting a microtube 202 into the bottom of a vertical channel 201, inputting a continuous phase solution 102 into a first straight channel 101, inputting a high-viscosity dispersed phase solution 204 into an inner diameter opening of the microtube 202 in the vertical channel 201, wherein the continuous phase solution 102 is partially poured into the inner diameter opening of the microtube 202 at a junction 203 under the action of the high-viscosity micro-droplet generation channel 303, so that the high-viscosity dispersed phase solution 204 does not completely wet a nozzle, and the high-viscosity dispersed phase solution 204 at the junction 203 is extruded, so that high-viscosity micro-droplets 304 with smaller area than the junction 203 are formed; by introducing the continuous phase solution 102 into one side of the first straight channel 101, the high viscosity dispersed phase solution 204 is introduced into the microtube 202 of the vertical channel 201, and the continuous phase solution 102 and the high viscosity dispersed phase solution 204 are introduced into the micro channel simultaneously or not simultaneously. When the continuous phase solution 102 passes through the high-viscosity micro-droplet generation channel 303, due to the structural arrangement of the high-viscosity micro-droplet generation channel 303, more shearing force is generated to change the state of the continuous phase solution 102, so that the continuous phase solution 102 can stably stay at the junction 203 in a small area, and further part of the continuous phase solution 102 is partially poured into the inner diameter opening of the micro-tube 202 at the junction 203, so that the high-viscosity dispersed phase solution 204 does not completely wet the nozzle, and the high-viscosity dispersed phase solution 204 at the junction 203 is extruded, so that the high-viscosity micro-droplet 304 with smaller area than the junction 203 is generated.
S502: stably outputting the high-viscosity micro-droplets from the third straight channel 401 through the conical channel 402; it should be noted that, the high-viscosity micro-droplet 304 generated in the previous step passes through the tapered channel 402 and is stably output from the third straight channel 401. The stable output can be understood that when the high-viscosity micro-droplets 304 first pass through the tapered channel 402, the longitudinal inner diameter and the transverse inner diameter of the tapered channel 402 are sequentially increased due to the improvement of the structure of the tapered channel 402, so that the generated high-viscosity micro-droplets stably flow out from the tapered channel 402 one by one, as shown in fig. 5; the jet flow phenomenon of the high-viscosity micro-droplets is effectively inhibited, a brand-new tip mode is generated, the high monodispersity of the high-viscosity micro-droplets is realized, the stability of the generation of the high-viscosity micro-droplets 304 is greatly improved, and the application range of the technology is enlarged.
S503: the size of the generated high-viscosity micro liquid 304 drop can be further controlled by changing the size of the micro tube 202 or adjusting the gap distance of the micro tube 202 inserted into the vertical channel 201; it should be noted that, under the condition of not increasing the complexity of the device/microfluidic chip and not changing the flow rate and the property of the fluid, the controllability and the stable generation of the high-viscosity micro-droplets 304 are realized, and compared with the traditional method, the generation size of the high-viscosity micro-droplets 304 is greatly reduced.
In addition, based on the high-viscosity micro-droplet 304 generated by the high-viscosity micro-droplet generating device, the high-viscosity micro-droplet generating device can meet the current requirement of most of the high-viscosity micro-droplet 304, breaks through the limit of the high-viscosity micro-droplet 304 generated by the traditional high-viscosity micro-droplet generating device, does not need external equipment, greatly reduces the complexity of the device and reduces the production input cost.
Specifically, fig. 6 shows a schematic diagram of droplet comparison in three different modes. Fig. 6a illustrates a conventional trickle mode, in which the round hole with a deeper gray level is a pipe outlet of the high viscosity dispersed phase solution (i.e., the high viscosity dispersed phase solution outlet 50), and the round hole with a shallower gray level is a correspondingly generated high viscosity micro droplet 70; it can be seen from fig. 6a that the size of the highly viscous micro-droplets 304 generated in the conventional trickle mode is almost the same as the size of the corresponding highly viscous dispersed phase solution outlet 50, and thus the size of the highly viscous micro-droplets 304 formed by breaking is large, for example, the highly viscous micro-droplets 304 generated in the conventional trickle mode are larger than 100 μm by selecting a tube with a nozzle of 100 μm or more, and thus the control of the size of the highly viscous micro-droplets 304 in the conventional trickle mode is very limited. Fig. 6b illustrates a newly generated tip mode according to the method provided by the embodiment of the present disclosure, in which the size of the corresponding high-viscosity micro-droplet 304 is much smaller than the size of the corresponding high-viscosity dispersed phase solution outlet 50, the size of the high-viscosity micro-droplet 304 formed by breaking is smaller, and the frequency of generation is stable, and the stretching, breaking and atomizing states are not presented. Fig. 6c shows a conventional jet pattern in which the correspondingly generated highly viscous micro-droplets 304 exhibit a longer stretching state, resulting in non-uniform droplet size, non-constant frequency, i.e., uncontrollable size. Based on this, the high-viscosity micro-droplet 304 generated by the high-viscosity micro-droplet generation method provided by the embodiment of the disclosure has smaller droplet size, stable generation frequency and controllable size, and can more satisfy the application in various fields of medicine research and development, material synthesis, chemical reaction and the like.
While the disclosure has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive.
Those skilled in the art will appreciate that the features recited in the various embodiments of the disclosure and/or the claims can be combined in a wide variety of combinations and/or combinations even if such combinations or combinations are not explicitly recited in the disclosure. In particular, the features recited in the various embodiments of the present disclosure and/or the claims may be variously combined and/or combined without departing from the spirit and teachings of the present disclosure. All such combinations and/or combinations fall within the scope of the present disclosure.
While the present disclosure has been shown and described with reference to certain exemplary embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present disclosure as defined by the appended claims and their equivalents. The scope of the disclosure should, therefore, not be limited to the above-described embodiments, but should be determined not only by the following claims, but also by the equivalents of the following claims.

Claims (9)

1. The high-viscosity micro-droplet generation device based on the three-dimensional micro-channel structure is characterized by comprising a micro-tube (202) and a micro-fluidic chip, wherein the three-dimensional micro-channel structure (100) arranged in the micro-fluidic chip is of a T-shaped structure and comprises
A continuous phase module (10) having a first straight channel (101) formed therein for inputting a continuous phase solution (102);
a disperse phase module (20) with a vertical channel (201) formed inside and used for extending a micro tube (202) and inputting a high-viscosity disperse phase solution (204) through the micro tube (202);
a high-viscosity micro-droplet module (30) with a second straight channel (301) of the T-shaped structure formed inside for generating high-viscosity micro-droplets (304); and
an outlet module (40) inside which a third straight channel (401) of the T-shaped structure is formed for outputting highly viscous micro-droplets (304);
the first straight channel (101), the second straight channel (301) and the third straight channel (401) are sequentially connected and communicated to form a main channel of the microfluidic chip, and central axes of the channels are overlapped; a group of boss structures (302) are symmetrically arranged in the second straight channel (301) near the inner walls of the two sides of the main channel, the outer end faces of the microtubes (202) extend into the vertical channel (201) and can be abutted against the outer end faces of the boss structures (302), so that a high-viscosity micro-droplet generation channel (303) is formed between the two boss structures (302), and the high-viscosity micro-droplet generation channel (303) is in a regular prismatic table shape; the junction of the high-viscosity micro-droplet generation channel (303) and the third straight channel (401) is also provided with a conical channel (402) for stably conveying the high-viscosity micro-droplet (304), and the high-viscosity micro-droplet (304) is output from the third straight channel (401) through the conical channel (402).
2. The device for generating high-viscosity micro-droplets based on a three-dimensional micro-channel structure according to claim 1, wherein the high-viscosity dispersed phase solution (204) is a fluid with a minimum viscosity of not less than 100 mPa-s.
3. The device for generating high-viscosity micro-droplets based on the three-dimensional micro-channel structure according to claim 1, wherein the horizontal width of the channel at the joint of the high-viscosity micro-droplet generation channel (303) and the third straight channel (401) is equal, the cross-sectional dimensions of the high-viscosity micro-droplet generation channel (303) and the tapered channel (402) which are oppositely arranged are gradually increased along the opposite direction of the joint, the longitudinal inner diameter of the tapered channel (402) is in gradient-like change, and the outer sections of the high-viscosity micro-droplet generation channel (303) and the tapered channel (402) are finally in sealing connection with the inner side wall of the main channel.
4. The device for generating high-viscosity micro-droplets based on the three-dimensional micro-channel structure according to claim 1, wherein the vertical channel (201) penetrates through the outside of the second straight channel (301) and does not completely penetrate through the outside, thereby a group of limiting structures (205) are symmetrically formed on two sides of the main channel, and a certain distance is kept between the outer end surface of the limiting structures (205) and the outer end surface of the main channel.
5. The device for generating high-viscosity micro-droplets based on the three-dimensional micro-channel structure according to claim 1, wherein the first straight channel (101), the vertical channel (201), the high-viscosity micro-droplet generation channel (303), the conical channel (402) and the third straight channel (401) are all integrally formed and prepared by a three-dimensional photo-curing molding method of a 3D printing technology, and the preparation material is photosensitive resin.
6. The high-viscosity micro-droplet generation device based on a three-dimensional micro-channel structure according to claim 1, wherein the longitudinal inner diameter of the first straight channel (101) is larger than the longitudinal inner diameter of the tapered channel (402), the longitudinal inner diameter of the tapered channel (402) is larger than the longitudinal inner diameter of the high-viscosity micro-droplet generation channel (303), and the longitudinal inner diameters of the first straight channel (101) and the third straight channel (401) are equal.
7. The device according to claim 6, wherein the cross sections of the first straight channel (101), the vertical channel (201) and the third straight channel (401) are round or rectangular, the inner diameters of the first straight channel (101) and the third straight channel (401) are 300 μm-800 μm, the inner diameter of the vertical channel (201) is 800 μm-1600 μm, the height of the boss structure (302) is 50 μm-300 μm, the inner diameter of the microtube (202) is 50 μm-800 μm, and the outer diameter thereof is 300 μm-1600 μm.
8. The high viscosity micro-droplet generator of claim 7, wherein said micro-pipe (202) is detachably connected to the vertical channel (201).
9. A method for high viscosity micro-droplet generation based on a three-dimensional micro-channel structure according to any of claims 1-8, characterized in that the method comprises:
inserting a microtube (202) into the bottom of a vertical channel (201), inputting a continuous phase solution (102) into a first vertical channel (101), inputting a high-viscosity dispersed phase solution (204) into an inner diameter opening of the microtube (202) in the vertical channel (201), and when the continuous phase solution (102) flows through the high-viscosity micro-droplet generation channel (303), partially pouring the continuous phase solution (102) into the inner diameter opening of the microtube (202) at a junction (203), so that the high-viscosity dispersed phase solution (204) does not completely wet a nozzle, and extruding the high-viscosity dispersed phase solution (204) at the junction (203) to generate high-viscosity micro-droplets (304) with smaller area than the junction (203); stably outputting the high-viscosity micro-droplets (304) from the third straight channel (401) through the conical channel (402);
the size of the generated high-viscosity micro-droplets (304) can be further controlled by changing the size of the micro-tube (202) and adjusting the gap distance of the micro-tube (202) inserted into the vertical channel (201).
CN202311511172.0A 2023-11-14 2023-11-14 High-viscosity micro-droplet generation device and method based on three-dimensional micro-channel structure Pending CN117483022A (en)

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