CN114471765A - Centrifugal liquid drop generating chip - Google Patents

Centrifugal liquid drop generating chip Download PDF

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Publication number
CN114471765A
CN114471765A CN202210056139.2A CN202210056139A CN114471765A CN 114471765 A CN114471765 A CN 114471765A CN 202210056139 A CN202210056139 A CN 202210056139A CN 114471765 A CN114471765 A CN 114471765A
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storage area
centrifugal
communication channel
fluid
chip
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CN114471765B (en
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陈辉
吴大林
何旭
苏辰宇
高亚钗
刘强
谈晓峰
吴靖轩
邓志国
刘华栋
刘东明
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Beijing Poly Micro Core Technology Co ltd
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Beijing Poly Micro Core Technology Co ltd
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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

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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)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

The invention provides a centrifugal liquid drop generating chip which comprises a chip body, wherein the chip body is provided with a first storage area and a second storage area, the first storage area is communicated with the second storage area through a communication channel with a hydrophobic effect, when the chip body rotates around the geometric center of the chip body, fluid in the first storage area can enter the communication channel under the action of centrifugal force, micro liquid drops are generated in the communication channel by utilizing the magnitude relation between the centrifugal force and the surface tension of the fluid, the generated micro liquid drops can enter the second storage area under the action of the centrifugal force, the fluid in the first storage area is one of water or oil, and the fluid in the second storage area is the other of water or oil. The invention can generate micro liquid drops by utilizing the magnitude relation between the rotating centrifugal force and the surface tension of the fluid, has simple structure and convenient use, and can accurately control the generation size of the liquid drops.

Description

Centrifugal liquid drop generating chip
Technical Field
The invention belongs to the technical field of micro-droplet generation, and particularly relates to a centrifugal droplet generation chip.
Background
The micro-droplets have the advantages of ultra-small volume, low sample consumption, high flux, high sensitivity, stable interior, controllability and the like, and are widely applied to the fields of biology, chemical analysis and detection, life science, theoretical calculation, organic synthesis, material chemistry and the like. The conventional droplet generation generally employs a flow focusing method. The principle of the method is that fluid flowing out of a capillary is driven by another fluid moving at a high speed, a stable cone is formed after the fluid is focused by a small hole, a micro jet flow is generated at the top end of the cone and penetrates through the small hole, and the jet flow is broken into monodisperse micro-droplets due to instability. The liquid drop generating method needs a precise injection pump to strictly control the flow rate of the fluid in the channel, and has complex operation and high requirements on instruments and equipment. In 1997, the m.nakajima group reported a stepped chip structure for droplet generation, which generated droplets by breaking through static instability when a fluid passed through three-dimensional steps. Although the method greatly avoids the influence of the flow velocity on the liquid drops, the height and the shape of the step are closely related to the stability and the uniformity of the liquid drop generation, and the processing requirement on the chip is high. In 2015, dupont and bin achieved droplet generation by micro-vibration of the capillary tip, but this method was more difficult to control accurately than the microfluidic chip. In addition, the planar microfluidic chip proposed in patent CN201710429242.6 needs to be connected with multiple pumps for assistance when generating droplets, and the apparatus is complex and has the potential of cross contamination. In view of the defects of the liquid drop generating method, the invention designs the centrifugal microfluidic chip which has a simple structure, is efficient to use and can accurately control the size of the liquid drop to generate the micro-liquid drop.
Disclosure of Invention
Therefore, an object of the present invention is to provide a centrifugal droplet generation chip, which can generate micro droplets by using the magnitude relationship between the rotational centrifugal force and the surface tension of a fluid, has a simple structure, is convenient to use, and can precisely control the generation size of the droplets.
In order to solve the above problems, the present invention provides a centrifugal droplet generation chip, including a chip body, the chip body having a first storage area and a second storage area, the first storage area and the second storage area being communicated through a communication channel having a hydrophobic effect, when the chip body rotates around its geometric center, a fluid in the first storage area can enter the communication channel under the action of a centrifugal force, and micro droplets are generated in the communication channel by using the magnitude relationship between the centrifugal force and the surface tension of the fluid, the generated micro droplets can enter the second storage area under the action of the centrifugal force, the fluid in the first storage area is one of water or oil, and the fluid in the second storage area is the other of water or oil.
In some embodiments, the first storage area and the second storage area are spaced apart from each other in a radial direction of the chip body, and the communication channel extends in the radial direction of the chip body.
In some embodiments, the flow area of the communication channel at both end positions is larger than the flow area at the intermediate position.
In some embodiments, the hydrophobic angle of the communication channel is no less than 100 °; and/or the radial extension length of the communication channel is 1 mm-3 cm, the axial depth is 10 μm-100 μm, the lengths of the two end positions are 1 mm-2 cm, the length of the middle position is 1 mm-2 cm, the circumferential width of the middle position is 10 μm-100 μm, and the circumferential widths of the two end positions are 50 μm-500 μm.
In some embodiments, the chip body has a central through hole for mounting a rotary drive shaft.
In some embodiments, the first storage region and/or the second storage region comprises a plurality of fan rings evenly or unevenly spaced around the central via; and/or the first storage area and/or the second storage area are circular rings concentric with the central through hole.
In some embodiments, the fan ring corresponds to a central angle of 0 ° to 360 °.
In some embodiments, the depth of the fan ring is 1 μm to 1mm, and the depth of the circular ring is 1 μm to 1 mm.
In some embodiments, the centrifugal microfluidic chip is made of a high molecular polymer.
The centrifugal micro-fluidic chip provided by the invention has the advantages that the generation of micro-droplets is a result of the combined action of centrifugal force and the surface hydrophobic property of a communication channel, when the chip body rotates to reach a certain high rotating speed, the generated centrifugal action firstly introduces fluid in a first storage area into the communication channel, then the centrifugal rotating speed is reduced to a certain threshold value, the centrifugal force is smaller than the surface tension of the fluid in the communication channel, the continuous fluid is cut off to form droplets, and the size of the droplets can be controlled by the time duration higher than the rotating speed of the certain threshold value.
Drawings
FIG. 1 is a schematic diagram of a centrifugal droplet generation chip according to an embodiment of the invention;
FIG. 2 is a schematic diagram of a centrifugal droplet generation chip according to another embodiment of the present invention;
FIG. 3 is a schematic diagram of a centrifugal droplet generation chip according to yet another embodiment of the present invention;
FIG. 4 is a schematic diagram of a centrifugal droplet generation chip according to yet another embodiment of the invention.
The reference numbers are given as:
1. a chip body; 11. a central through hole; 2. a first storage area; 3. a second storage area; 4. a communication channel.
Detailed Description
Referring to fig. 1 to 4 in combination, according to an embodiment of the present invention, there is provided a centrifugal droplet generation chip, including a chip body 1, the chip body 1 having a first storage area 2 and a second storage area 3, the first storage area 2 and the second storage area 3 being in communication with each other through a communication channel 4 having a hydrophobic effect (in one embodiment, the hydrophobic angle of the communication channel 4 is not less than 100 °), when the chip body 1 rotates around its geometric center, a fluid in the first storage area 2 can enter the communication channel 4 under the action of a centrifugal force, and micro droplets are generated in the communication channel 4 by using the magnitude relationship between the centrifugal force and the surface tension of the fluid, the generated micro droplets can enter the second storage area 3 under the action of the centrifugal force, the fluid in the first storage area 2 is one of water or oil, the fluid in the second storage zone 3 is the other of water or oil. In the technical scheme, the generation of micro-droplets is a result of the combined action of centrifugal force (determined by adjusting the rotation speed) and the surface hydrophobic property of a communication channel 4, when the chip body 1 rotates to a certain high rotation speed, the generated centrifugal action firstly introduces fluid in the first storage area 2 into the communication channel 4, then the centrifugal rotation speed is reduced to a certain threshold value, the centrifugal force is smaller than the surface tension of the fluid in the communication channel 4, the continuous fluid is cut off to form droplets, and the size of the droplets can be controlled by the time duration higher than the certain threshold rotation speed.
Specifically, when the generated micro droplets are water-in-oil droplets, the fluid in the first storage region 2 is water, and the fluid in the second storage region 3 is oil; when the generated micro droplets are oil-in-water type droplets, the fluid in the first storage region 2 is oil, and the fluid in the second storage region 3 is water.
In some embodiments, the first storage area 2 and the second storage area 3 are spaced apart from each other in a radial direction of the chip body 1, and the communication channel 4 extends in the radial direction of the chip body 1, so that the circulation efficiency of the fluid in the first storage area 2, the communication channel 4 and the second storage area 3 can be improved, and further the generation efficiency of the micro-droplets can be improved.
In some embodiments, the flow area of the two end positions of the communication channel 4 is larger than that of the middle position, that is, the communication channel 4 is formed into a narrow bridge structure with two wide ends and a narrow center in appearance, the structure with two wide ends is beneficial to the flow of the fluid, the fluid is convenient to form liquid drops on a hydrophobic surface under the action of surface tension, and the narrow center part is beneficial to the dispersion of the fluid from a continuous phase into discrete liquid drops.
In a specific embodiment, the communication channel 4 has a radial extension length of 1mm to 3cm, an axial depth of 10 μm to 100 μm, a length of 1mm to 2cm at both end positions, a length of 1mm to 2cm at the middle position, a circumferential width of 10 μm to 100 μm at the middle position, and a circumferential width of 50 μm to 500 μm at both end positions.
The chip body 1 has a central through hole 11, the central through hole 11 is used for installing a rotary driving shaft, for example, a related power output end of a centrifuge, so as to generate a driving force for rotating the chip body 1, and adjust the centrifugal force and the duration of a certain centrifugal force according to the generation requirement of micro-droplets.
In some embodiments, the first storage area 2 and/or the second storage area 3 comprise a plurality of fan-shaped rings evenly or unevenly spaced around the central through hole 11; and/or the first storage area 2 and/or the second storage area 3 are/is a circular ring concentric with the central through hole 11, and further, the central angle corresponding to the fan ring is 0-360 degrees.
With particular reference to fig. 1 to 4, wherein the first storage area 2 in fig. 1 is a uniformly or non-uniformly spaced sector ring and the second storage area 3 is a circular ring; in fig. 2, the first storage area 2 is a fan ring with uniform or non-uniform intervals, and the second storage area 3 is a fan ring with uniform or non-uniform intervals; in fig. 3, the first storage area 2 is a ring, and the second storage area 3 is also a ring; in fig. 4, the first storage area 2 is a circular ring, and the second storage area 3 is a fan ring with uniform or non-uniform intervals; the number of the fan rings and the number of the units are not limited, and can be adjusted according to specific use requirements and the appearance of the chip.
In some embodiments, the depth of the fan ring is 1 μm to 1mm, and the depth of the circular ring is 1 μm to 1 mm.
In some embodiments, the centrifugal microfluidic chip is made of a high molecular polymer, such as one of polymethyl methacrylate, polycarbonate, cyclic olefin copolymer, polystyrene, polypropylene, and polyetherimide.
A specific example is given below to further illustrate the technical solution of the present invention.
1) When the centrifugal micro-fluidic chip is used for generating water-in-oil type droplets, the second storage area 3 is used as an oil phase storage area, is far away from the central area and is close to the outer edge of the chip, is in a hollow circular ring shape with a symmetrical center, has the same bending radian as the disk surface radian of the centrifugal micro-fluidic chip, has an opening size forming an included angle of 90 degrees with the central axis, and has the depth of 400 mu m. The first storage area 2 is used as an aqueous storage area, is close to the central area, surrounds the central area at a certain angle, is shaped like a sector ring, and forms an included angle of 90 degrees with the symmetrical axis of the chip body at the peripheral edge line of the sector ring, and the depth of the included angle is 350 mu m. The communicating channel 4 is connected with the oil phase storage area and the water phase storage area, is in a narrow bridge structure with two wide ends and a narrow center, and has the total length of 5mm, the lengths of the two end areas are respectively 1mm, the length of the middle area is 3mm, the width of the port of the two end areas is 50 mu m, the width of the middle area is 20 mu m, and the depth is 20 mu m. The centrifugal microfluidic chip is made of cyclic olefin copolymer, and the hydrophobic angle of the communicating channel 4 reaches 110 degrees after surface hydrophobic treatment. Setting a proper centrifugal rotating speed program, when the disc reaches a certain high rotating speed, generating a centrifugal effect to firstly introduce the fluid into the flow channel, then reducing the centrifugal rotating speed to a certain threshold value, wherein the centrifugal force is smaller than the surface tension of the liquid in the hydrophobic flow channel, and cutting off the continuous fluid to form liquid drops; droplet size may be controlled by the length of time that the centrifugal spin rate is above a certain threshold. The communication channels 4 can be arranged in large numbers according to the chip layout, so that the centrifugal microfluidic chip can generate thousands of droplets at a time.
2) When the centrifugal micro-fluidic chip is used for generating oil-in-water type droplets, the second storage area 3 is used as a water phase storage area, is far away from the central area and is close to the outer edge of the chip, is in a hollow circular ring shape with a symmetrical center, has the same bending radian as the disk surface radian of the centrifugal micro-fluidic chip, has an opening size forming an included angle of 90 degrees with the central axis, and has the depth of 400 mu m. The first storage area 2 is used as an oil phase storage area, is close to the central area, surrounds the central area at a certain angle, is shaped as a sector ring, and forms a 90-degree included angle with a symmetrical axis of a chip body of the sector ring, and the depth of the sector ring is 350 mu m. The communicating channel 4 is connected with the water phase storage area and the oil phase storage area, is in a narrow bridge structure with two wide ends and a narrow center, and has the total length of 5mm, the lengths of the two end areas are respectively 1mm, the length of the middle area is 3mm, the width of the port of the two end areas is 50 mu m, the width of the middle area is 20 mu m, and the depth is 20 mu m. The centrifugal micro-fluidic chip is made of cycloolefin copolymer, and the hydrophobic angle reaches 110 degrees after the communicating channel is subjected to surface hydrophobic treatment. Setting a proper centrifugal rotating speed program, when the disc reaches a certain high rotating speed, generating a centrifugal effect to firstly introduce the fluid into the flow channel, then reducing the centrifugal rotating speed to a certain threshold value, wherein the centrifugal force is smaller than the surface tension of the liquid in the hydrophobic flow channel, and cutting off the continuous fluid to form liquid drops; droplet size may be controlled by the length of time that the centrifugal spin rate is above a certain threshold. The communication channels 4 can be arranged in large numbers according to the chip layout, so that the centrifugal microfluidic chip can generate thousands of droplets at a time.
It is readily understood by a person skilled in the art that the advantageous ways described above can be freely combined, superimposed without conflict.
The present invention is not limited to the above preferred embodiments, and any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention. The above is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the technical principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims (9)

1. A centrifugal droplet generation chip, characterized by comprising a chip body (1), the chip body (1) is provided with a first storage area (2) and a second storage area (3), the first storage area (2) is communicated with the second storage area (3) through a communication channel (4) with hydrophobic effect, when the chip body (1) rotates around the geometric center thereof, the fluid in the first storage area (2) can enter the communication channel (4) under the action of centrifugal force, and micro-droplets are generated in the communication channel (4) by utilizing the magnitude relation between the centrifugal force and the surface tension of the fluid, the generated micro-droplets can enter the second storage area (3) under the action of the centrifugal force, the fluid in the first storage area (2) is one of water or oil, and the fluid in the second storage area (3) is the other one of water or oil.
2. Centrifugal droplet generation chip according to claim 1, wherein the first storage area (2) and the second storage area (3) are spaced apart in a radial direction of the chip body (1), the communication channel (4) extending in the radial direction of the chip body (1).
3. Centrifugal droplet generation chip according to claim 2, wherein the flow area of the communication channel (4) is larger at both end positions than at the middle position.
4. Centrifugal droplet generation chip according to claim 1, wherein the hydrophobic angle of the communication channel (4) is not lower than 100 °; and/or the radial extension length of the communication channel (4) is 1 mm-3 cm, the axial depth is 10 μm-100 μm, the lengths of the two end positions are 1 mm-2 cm, the length of the middle position is 1 mm-2 cm, the circumferential width of the middle position is 10 μm-100 μm, and the circumferential widths of the two end positions are 50 μm-500 μm.
5. Centrifugal droplet generation chip according to claim 1, wherein the chip body (1) has a central through hole (11), the central through hole (11) being for mounting a rotary drive shaft.
6. Centrifugal droplet generation chip according to claim 5, wherein the first storage area (2) and/or the second storage area (3) comprise a plurality of fan rings evenly or unevenly spaced around the central through hole (11); and/or the first storage area (2) and/or the second storage area (3) are circular rings concentric with the central through hole (11).
7. The centrifugal droplet generation chip of claim 6, wherein the fan ring corresponds to a central angle of 0 ° to 360 °.
8. The centrifugal droplet generation chip of claim 6, wherein the fan ring has a depth of 1 μm to 1mm and the circular ring has a depth of 1 μm to 1 mm.
9. The centrifugal droplet generation chip of claim 1, wherein the centrifugal microfluidic chip is made of a high molecular polymer.
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