LU502120B1 - Multi-channel liquid drop formation device and method based on macroporous perfusion microsphere - Google Patents

Multi-channel liquid drop formation device and method based on macroporous perfusion microsphere Download PDF

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Publication number
LU502120B1
LU502120B1 LU502120A LU502120A LU502120B1 LU 502120 B1 LU502120 B1 LU 502120B1 LU 502120 A LU502120 A LU 502120A LU 502120 A LU502120 A LU 502120A LU 502120 B1 LU502120 B1 LU 502120B1
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LU
Luxembourg
Prior art keywords
perfusion
microsphere
macroporous
capillary tube
liquid drop
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Application number
LU502120A
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French (fr)
Inventor
Xiaofei Wang
Bo Zhang
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Jinjiang Jingchun Tech Co Ltd
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Priority to LU502120A priority Critical patent/LU502120B1/en
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Publication of LU502120B1 publication Critical patent/LU502120B1/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
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/41Emulsifying
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/45Mixing liquids with liquids; Emulsifying using flow mixing
    • B01F23/451Mixing liquids with liquids; Emulsifying using flow mixing by injecting one liquid into another
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71Feed mechanisms
    • B01F35/717Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/7174Feed mechanisms characterised by the means for feeding the components to the mixer using pistons, plungers or syringes
    • 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
    • B01L2200/06Fluid handling related problems
    • B01L2200/0673Handling of plugs of fluid surrounded by immiscible fluid
    • 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
    • B01L2300/0832Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0838Capillaries

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Manufacturing Of Micro-Capsules (AREA)

Abstract

The multi-channel liquid drop formation device based on the macroporous perfusion microsphere is provided with a capillary tube, the macroporous perfusion microsphere, a liquid conveying device and a liquid drop collecting device; the macroporous perfusion microsphere is fixed on the capillary port, and has a plurality of perforating pore channels; the capillary is a dispersed phase passage; the liquid conveying device is used for conveying the dispersed phase; the liquid drop collecting device is used for containing the continuous phase and collecting liquid drops. Based on the Key Stone Effect, the perfusion microsphere is fixed at the port of the capillary tube, and then one end of the capillary tube with the macroporous perfusion microsphere is placed into a container containing the fluorocarbon-40 continuous phase. The other end of the capillary tube with the macroporous perfusion microsphere is connected with the syringe by using a PEEK hose.

Description

DESCRIPTION LU502120 MULTI-CHANNEL LIQUID DROP FORMATION DEVICE AND METHOD BASED
ON MACROPOROUS PERFUSION MICROSPHERE
TECHNICAL FIELD The application relates to the field of microfluidic liquid drop formation, and in particular to a multi-channel liquid drop formation device and a method based on macroporous perfusion microsphere.
BACKGROUND The microfluidic liquid drop preparation technology is a new micro liquid drop preparation and operation technology developed in recent years, two immiscible liquid phases are used to separate the fluid into liquid drops with certain volume by using shearing force and surface tension. Microfluidic liquid drop technology has attracted extensive attention and researches in recent years due to its advantages in mass transfer, heat transfer, substance exchange, and quantitative control.
At present, the preparation of liquid drops is mainly through the cross and relative movement between continuous phase and dispersed phase, thus forming liquid drops. For example, the pressure pump is used to pass the dispersed phase and the continuous phase through the T-channel method, flow focusing method and coaxial flow method. It is the dispersed phase liquid that generates liquid drops under the action of the continuous phase. The above three methods are widely used in the chip method and capillary tube method. However, in actual application, the power sources (pressure pumps, injection pumps, etc.) of the dispersed phase and the continuous phase easily become instable during long-time operation, thus affecting the uniformity and consistency of the formed liquid drops size. Another disadvantage is the high-density multi-channel parallelism cannot be realized, and the liquid drop volumes are on the nanometer scale or smaller. How to realize large-scale preparation, is also an important challenge.
SUMMARY The application aims to provide a multi-channel liquid drop formation device and method based on macroporous perfusion microsphere, which has simple liquid drop formation device,
good reproducibility between times, and is easy to prepare batch parallel liquid drop preparation, 20 and remarkably improve the liquid drop preparation flux and precision.
The multi-channel liquid drop formation device based on the macroporous perfusion microsphere is provided with a capillary tube, the macroporous perfusion microsphere, a liquid conveying device and a liquid drop collecting device; the macroporous perfusion microsphere is fixed on the capillary port, and has a plurality of perforating pore channels; the capillary is a dispersed phase passage; the liquid conveying device is used for conveying the dispersed phase; the liquid drop collecting device is used for containing the continuous phase and collecting liquid drops.
The dispersed phase is conveyed into the capillary tube by the liquid conveying device at a certain flow rate, after passing through the pore channel in the macroporous perfusion microsphere, is cut into liquid drops with a certain size, and is collected in the container containing the continuous phase.
The liquid conveying device can adopt a device capable of conveying liquid at an accurate flow rate, such as an injection pump, a syringe barrel, a peristaltic pump, a high-pressure pump and the like.
In the application, the inside of the macroporous perfusion microsphere is provided with abundant micron-sized pore channels for realizing the purpose of multi-channel liquid drop formation.
The material of the capillary tube used in the present application may be an organic polymer material such as polyetheretherketone (PEEK) or an inorganic material such as quartz or metal. The inner diameter of the capillary may be 10-500 pum.
The material of the macroporous perfusion microsphere can be silicon dioxide inorganic material, organic polymer material, or organic-inorganic hybrid material, the macroporous perfusion microsphere contained abundant macropores with the inner diameter of about 1 um.
The method for fixing the macroporous perfusion microsphere at the port of capillary tube can be based on physical methods such as a method based on Key Stone Effect, thermal deformation mechanical extrusion, or the macroporous perfusion microsphere can be adhered at the nozzle by using a chemical reaction method.
In the application, after the dispersed phase prepares the liquid drops through the 5021 20 macroporous perfusion microsphere, based on the difference between the density of the continuous phase and the density of the dispersed phase, the liquid drops can float to the liquid level of the continuous phase, can also sink to the bottom of the continuous phase, or are uniformly dispersed in the continuous phase.
In the single liquid drop preparation process, a plurality of capillary tubes provide with the macroporous perfusion microsphere can be used in parallel, so that multi-channel parallel multi-channel liquid drop preparation is realized.
A multi-channel liquid drop formation method based on the macroporous perfusion microsphere includes the following specific steps: Based on the Key Stone Effect, the perfusion microsphere is fixed at the port of the capillary tube, and then one end of the capillary tube with the macroporous perfusion microsphere is placed into a container containing the fluorocarbon-40 continuous phase. The other end of the capillary tube with the macroporous perfusion microsphere is connected with the syringe by using a PEEK hose. Water/methanol (1/1, v/v) is used as the dispersed phase, and the continuous phase is pressed into the capillary tube to rapidly generate a large number of liquid drops.
The capillary tube can adopt a capillary tube made of quartz material, the inner diameter of the capillary tube is 100 um, and the length of the capillary tube is 10 cm; the perfusion microsphere may have an outer diameter of 100 um, and the continuous phase may be pressed into the capillary tube by manually pressing 1 mL of the continuous phase into the capillary tube.
The liquid drop formation device is simple, the liquid drop preparation flux is high, and the reproducibility of the liquid drop size is good.
The application overcomes the defects of the prior liquid drop preparation, utilizes the abundant and uniform pores in the macroporous perfusion microsphere, remarkably improves the density of the liquid drop preparation channel, greatly improves the liquid drop generation flux, can realize the large-scale preparation of liquid drops in a short time, can control the high uniformity of the size of the liquid drops, and is easy to realize the batch parallel liquid drop preparation, so has great application potential.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a schematic diagram of device for generating liquid drops through capillary tube. 5001 20 FIG. 2 is a schematic diagram of multi-channel liquid drop formation device in embodiment 1 through the single-capillary tube.
FIG. 3 is a schematic diagram of multi-channel liquid drop formation device in embodiment 2 through 8 parallel capillary tube.
FIG. 4 is an optical microscope diagram of liquid drop with high uniform size obtained in embodiment 3.
DESCRIPTION OF THE APPLICATION The application is further described below with reference to the accompanying figures and several alternative embodiments. It should be noted that the present application is not limited to the following embodiments. In the embodiments where specific techniques and conditions are not indicated, the procedures are carried out according to the techniques and conditions described in the literature in the art or according to the product specifications, and the reagents or instruments used without indicating the manufacturer, are conventional products that are commercially available.
Embodiment 1: Establishment of a multi-channel liquid drop formation with an inner diameter of 100 um Referring to FIG. 1 and FIG. 2, a 10 cm capillary tube 3 with an inner diameter of 100 um is cut, a dispersed phase 10 is pressed into the parallel capillary tube 3 by an injection pump 5, a macroporous perfusion microsphere 7 with an outer diameter of 100 um is fixed at the port of the capillary tube 3 based on the Key Stone Effect, one end of the capillary tube 3 with the macroporous perfusion microsphere is placed into a container 8 containing a fluorocarbon-40(FC-40) 4 continuous phase, and the other end of the capillary tube 3 is connected with the syringe 1 by a PEEK hose 2. Water/methanol (1/1, v/v) is used as the dispersed phase 10, 1 mL of the continuous phase 9 is manually pressed into the capillary tube 3, and a large number of liquid drops 11 could be formed rapidly.
Embodiment 2: Establishment of multi-channel liquid drop formation device in embodiment 2 through 8 parallel capillary tube.
Eight quartz capillary tubes 3 with a length of 10 cm and an inner diameter of 100 um are cut. Using the method in embodiment 1, a perfusion microsphere with an outer diameter of 100 um is fixed at the port of each capillary tube, based on the Key Stone Effect. One end of eaƧh 5021 20 capillary tube with the macroporous perfusion microsphere 1s placed into a container containing FC-40 4 continuous phase, and the other end is connected with the syringe by a PEEK hose 2.
The dispersed phase is divided into eight channels by four Tee-junctions 6 (as shown in FIG. 3). Water/methanol (1/1, v/v) is used as the dispersed phase, and syringe pump 5 is used to press the dispersed phase into eight parallel capillary tubes 3 at the flow rate of 500 uL/min, the parallel multi-channel capillary liquid drop formation device 1s constructed.
Embodiment 3: Formation of liquid drop of high uniform size Using the liquid drop generating device constructed in embodiment 1, FC-40 1s used as the continuous phase and water/methanol (1/1, v/v) as the dispersed phase, and the dispersed phase is injected into the continuous phase by a precise syringe pump at a flow rate of 50 uL/min to prepare liquid drops; then observing and measuring size of liquid drops under the microscope. By measuring the diameters of the 50 liquid drops, the CV value of the obtained liquid drops is calculated: 3%, indicating that the obtained liquid drops had a high uniform in size (Fig. 4).
The application consists of the capillary tube, the macroporous perfusion microsphere, the liquid conveying device and a liquid drop collecting device, where the macroporous perfusion microsphere is fixed on the port of the capillary tube, the capillary tube is placed below a liquid level of the continuous phase, and the dispersed phase is injected into the continuous phase through the capillary tube at a certain flow rate. When the dispersed phase passes through the macroporous perfusion microsphere, a multi-channel micro-fluid flow is formed through the rich and uniform pores in the macroporous perfusion microsphere and is cut into liquid drops at the outlet of the pores. The preparation device is simple, the method is reliable, and the size of obtained liquid drops has good uniformity; a large number of pores with the diameter of 1 um penetrate through the microsphere, thus forming a plurality of liquid drop formation micro-channels, and the liquid drop formation flux is greatly improved; using the device to prepare liquid drops, it is easier to realize the precise control of liquid drop size and formed flux, the application overcomes the shortcomings that conventional microfluidic chips have few channels and are easy to be blocked and the formed flux of liquid drops is low.

Claims (10)

CLAIMS LU5S02120
1. A multi-channel liquid drop formation device based on the macroporous perfusion microsphere, which is characterized in comprising a capillary tube, a macroporous perfusion microsphere, a liquid conveying device and a liquid drop collecting device; the macroporous perfusion microsphere is fixed on the capillary port, and has a plurality of perforating pore channels; the capillary is a dispersed phase passage; the liquid conveying device is used for conveying the dispersed phase; the liquid drop collecting device is used for containing the continuous phase and collecting liquid drops.
2. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the dispersed phase is conveyed into the capillary tube by the liquid conveying device at a certain flow rate, after passing through the pore channel in the macroporous perfusion microsphere, is cut into liquid drops with a certain size, and is collected in the container containing the continuous phase.
3. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the liquid conveying device can adopt a device capable of conveying liquid at an accurate flow rate, such as an injection pump, a syringe barrel, a peristaltic pump, a high-pressure pump and the like.
4. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the material of the capillary tube used in the present application may be an organic polymer material such as polyetheretherketone (PEEK) or an inorganic material such as quartz or metal.
5. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the inner diameter of the capillary may be 10-500 pm.
6. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the material of the macroporous perfusion microsphere can be silicon dioxide inorganic material, organic polymer material, or organic-inorganic hybrid material.
7. The multi-channel liquid drop formation device based on the macroporous perfusion 502120 microsphere according to claim 1, which is characterized in that the macroporous perfusion microsphere contained abundant macropores with the inner diameter of about 1um.
8. The multi-channel liquid drop formation device based on the macroporous perfusion microsphere according to claim 1, which is characterized in that the method for fixing the macroporous perfusion microsphere at the port of capillary can be based on physical methods such as a mothod based on KeyStone Effect, thermal deformation mechanical extrusion and the like, or the macroporous perfusion microsphere can be adhered at the nozzle by using a chemical reaction method.
9. A multi-channel liquid drop formation method based on the macroporous perfusion microsphere includes the following specific steps: based on the Key Stone Effect, the perfusion microsphere is fixed at the port of the capillary tube, and then one end of the capillary tube with the macroporous perfusion microsphere is placed into a container containing the fluorocarbon-40 continuous phase; the other end of the capillary tube with the macroporous perfusion microsphere is connected with the syringe by using a PEEK hose; water/methanol (1/1, v/v) is used as the dispersed phase, and the continuous phase is pressed into the capillary tube to rapidly generate a large number of liquid drops.
10. The multi-channel liquid drop formation method based on the macroporous perfusion microsphere according to claim 9, which is characterized in that the capillary tube can adopt a capillary tube made of quartz material, the inner diameter of the capillary tube is 100 um, and the length of the capillary tube is 10 cm; the perfusion microsphere may have an outer diameter of 100 um, and the continuous phase may be pressed into the capillary tube by manually pressing 1 mL of the continuous phase into the capillary tube.
LU502120A 2022-05-19 2022-05-19 Multi-channel liquid drop formation device and method based on macroporous perfusion microsphere LU502120B1 (en)

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LU502120A LU502120B1 (en) 2022-05-19 2022-05-19 Multi-channel liquid drop formation device and method based on macroporous perfusion microsphere

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LU502120A LU502120B1 (en) 2022-05-19 2022-05-19 Multi-channel liquid drop formation device and method based on macroporous perfusion microsphere

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Effective date: 20221121