CN113967490A - Array type micro-operation chip, operation system and operation method - Google Patents

Array type micro-operation chip, operation system and operation method Download PDF

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Publication number
CN113967490A
CN113967490A CN202111444729.4A CN202111444729A CN113967490A CN 113967490 A CN113967490 A CN 113967490A CN 202111444729 A CN202111444729 A CN 202111444729A CN 113967490 A CN113967490 A CN 113967490A
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Prior art keywords
substrate
contacts
controller
area
chip
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CN202111444729.4A
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宦智杰
张哲敏
马玮城
郑雄标
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Xiamen University of Technology
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Xiamen University of Technology
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Priority to CN202111444729.4A priority Critical patent/CN113967490A/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
    • B01L3/50Containers 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
    • 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
    • B01L3/50273Containers 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 the means or forces applied to move the fluids
    • 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
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic

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

Abstract

The invention provides an array type micro-operation chip, an operation system and an operation method, comprising the following steps: a first substrate, an intermediate layer, and a second substrate; the central part of the middle layer is provided with an operation area, a first microfluidic channel arranged on the first side of the operation area and a second microfluidic channel arranged on the second side of the operation area; the center part of the upper surface of the first substrate is provided with a plurality of first contacts which are electrically connected to a plurality of first edge electrodes at the end part of the first substrate, the center part of the lower surface of the second substrate is provided with a plurality of second contacts which are electrically connected to a plurality of second edge electrodes at the end part of the second substrate, and the first edge electrodes and the second edge electrodes are used for being electrically connected with the output end of a controller; a plurality of first contacts are in contact with a first surface of an operational area and a plurality of second contacts are in contact with a second surface of the operational area. The problems that the operation force is weak and the controllable area is small in the electric field to micron-scale particles are solved.

Description

Array type micro-operation chip, operation system and operation method
Technical Field
The invention relates to the field of micro control, in particular to an array type micro operation chip, an operation system and an operation method.
Background
Conventional particle manipulation methods, such as passive particle manipulation based on fluid dynamics, have shortcomings in cell manipulation accuracy and flexibility.
The micro-fluidic control based on electric control has the advantages of high accuracy and flexible control, but at the present stage, the effect of controlling cells in a wide area of the two-dimensional microelectrode micro-fluidic chip concentrated on a single plane is poor due to the defects of weaker operating force, smaller controllable area and the like of an electric field on the control of micron-scale particles; the micro-fluidic chip with the three-dimensional microelectrode structure overcomes the attenuation of an electric field on a channel to a certain extent through reasonable design, but has complex processing technology and high cost, and is difficult to apply in actual production and life.
In view of this, the present application is presented.
Disclosure of Invention
The invention discloses an array type micro-operation chip, an operation system and an operation method, and aims to solve the problems that in the prior art, the operation force is weak and a controllable area is small for micron-scale particles in an electric field.
The first embodiment of the present invention provides an array type micro-operation chip, including: a first substrate, an intermediate layer, and a second substrate;
wherein an upper surface of the first substrate is in contact with a first surface of the intermediate layer and a lower surface of the second substrate is in contact with a second surface of the intermediate layer;
the central part of the middle layer is provided with an operation area, a first microfluidic channel arranged on the first side of the operation area and a second microfluidic channel arranged on the second side of the operation area;
a plurality of first contacts are configured at the central part of the upper surface of the first substrate, the first contacts are electrically connected to a plurality of first edge electrodes at the end part of the first substrate, and the first edge electrodes are used for being electrically connected with an output end of a controller;
a plurality of second contacts are arranged at the central part of the lower surface of the second substrate, the plurality of first contacts are electrically connected to a plurality of second edge electrodes at the end part of the second substrate, and the second edge electrodes are used for being electrically connected with an output end of a controller;
wherein a plurality of the first contacts are in contact with a first surface of the operational area and a plurality of the second contacts are in contact with a second surface of the operational area.
Preferably, the first microfluidic channel and the second microfluidic channel are corrugated channels.
The end point of the first microfluidic channel, which is far away from the operation area, is provided with an inlet, and the end point of the second microfluidic channel, which is far away from the operation area, is provided with an outlet, wherein the inlet is used for connecting an injector, and the outlet is used for connecting a waste liquid pool.
Preferably, the material of the intermediate layer is PDMS.
Preferably, the first substrate and the second substrate are glass substrates.
Preferably, a projection of each first contact point perpendicular to the operating region and each second contact point are not in contact with each other.
The second embodiment of the invention provides an array type micro-operation system, which comprises a controller, a signal generator, an electron microscope, an industrial camera and an upper computer;
the output of signal generator with the input electrical connection of controller, the output of controller is with a plurality of first edge electrode, a plurality of second edge electrode electrical connection, the electron microscope configuration is in operating area's top, the electron microscope's output with the input electrical connection of industry camera, the output of industry camera with the input electrical connection of host computer, the output of host computer with the input electrical connection of controller.
Preferably, the chip model of the controller is STM32F 103.
A third embodiment of the present invention provides a control method as described above, including:
receiving current position information of particles on an operation area and target position information of the particles, wherein the current position information is collected by the electron microscope and the industrial camera and then sent to the upper computer;
generating a control signal based on the current position information and the target position information, wherein the control signal is used for switching on and off a first edge electrode or a second edge electrode to enable the particles to move to the target position.
According to the array type micro-operation chip, the operation system and the operation method provided by the invention, the operation area, the first micro-fluidic channel and the second micro-fluidic channel are arranged on the middle layer, wherein particles flow from the first micro-fluidic channel to the operation area and then flow to the second micro-fluidic channel, the plurality of first contacts arranged on the first substrate are contacted with the first surface of the operation area, the plurality of second contacts arranged on the second substrate are contacted with the second surface of the operation area, and alternating levels are respectively provided for the contacts through the first edge electrode and the second edge electrode, so that the particles on the operation area can move from the current position to the target position along with the alternating levels. The problems that in the prior art, the operation force is weak and the controllable area is small for micron-scale particles in an electric field are solved.
Drawings
FIG. 1 is a schematic diagram of a split structure of an array-type micro-manipulation chip according to an embodiment of the present invention;
FIG. 2 is a side view of an array type micro-manipulation chip according to an embodiment of the present invention;
FIG. 3 is a schematic structural diagram of an array-type micro-manipulation chip according to an embodiment of the present invention;
FIG. 4 is a schematic diagram of a second substrate structure provided in an embodiment of the invention;
FIG. 5 is a schematic view of a first substrate structure provided in an embodiment of the present invention;
FIG. 6 is a schematic diagram of an interlayer structure provided by an embodiment of the present invention;
FIG. 7 is a block diagram of an array-type micro operating system according to an embodiment of the present invention;
FIG. 8 is a schematic diagram of particle movement provided by an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings of the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention. Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.
The following detailed description of specific embodiments of the invention refers to the accompanying drawings.
The invention discloses an array type micro-operation chip, an operation system and an operation method, and aims to solve the problems that in the prior art, the operation force is weak and a controllable area is small for micron-scale particles in an electric field.
Referring to fig. 1 to 6, a first embodiment of the invention provides an array type micro-operation chip, including: a first substrate 1, an intermediate layer 2, and a second substrate 3;
wherein the upper surface of the first substrate 1 is in contact with the first surface of the intermediate layer 2 and the lower surface of the second substrate 3 is in contact with the second surface of the intermediate layer 2;
the central part of the intermediate layer 2 is provided with an operating area 21, a first microfluidic channel 22 arranged on a first side of the operating area 21, and a second microfluidic channel 23 arranged on a second side of the operating area 21;
a plurality of first contacts 12 are arranged at the center of the upper surface of the first substrate 1, the plurality of first contacts 12 are electrically connected to a plurality of first edge electrodes 11 at the ends of the first substrate 1, and the first edge electrodes 11 are used for being electrically connected with the output end of a controller 41;
a plurality of second contacts 32 are disposed at a central portion of a lower surface of the second substrate 3, a plurality of the first contacts 12 are electrically connected to a plurality of second edge electrodes 31 at end portions of the second substrate 3, and the second edge electrodes 31 are used for electrically connecting with an output terminal of a controller 41;
wherein a plurality of said first contacts 12 are in contact with a first surface of said operating area 21 and a plurality of said second contacts 32 are in contact with a second surface of said operating area 21.
It should be noted that the operation of the micro-fluidic control on the particles has the advantages of high accuracy and flexible control, but the defects of weak operation force and small controllable area exist in the stage of electric field on the operation of the micro-scale particles, and in particular, the effect of controlling cells in a wide area of a two-dimensional microelectrode micro-fluidic chip concentrated on a single plane is not good, because the dielectrophoresis force generated by the electric field on the particles is a short-range force and is attenuated rapidly along with the increase of the electrode distance, the electrodes need to be approached as much as possible when the structure is designed, so that a sufficiently large effective electric field can be generated. However, it is difficult to apply an external voltage by distributing the electrodes too close together in a single plane; the micro-fluidic chip with the three-dimensional microelectrode structure overcomes the attenuation of an electric field on a channel to a certain extent through reasonable design, but the processing technology is complex and the cost is high, so that the micro-fluidic chip is difficult to apply in actual production and life.
In this embodiment, by providing the intermediate layer 2 with an operation area 21, a first microfluidic channel 22 and a second microfluidic channel 23, wherein the particles flow from the first microfluidic channel 22 to the operation area 21 and then to the second microfluidic channel 23, the plurality of first contacts 12 disposed on the first substrate 1 are in contact with the first surface of the operation area 21, the plurality of second contacts 32 disposed on the second substrate 3 are in contact with the second surface of the operation area 21, and the contacts are respectively provided with alternating levels through the first edge electrode 11 and the second edge electrode 31, so that the particles on the operation area 21 can move from the current position to the target position with the alternating levels. The problem of among the prior art, it is difficult to distribute the electrode on single plane and close too hardly exert external voltage is solved.
In this embodiment, the first microfluidic channel 22 and the second microfluidic channel 23 may be corrugated channels.
Wherein, the end point of the first microfluidic channel 22 far away from the operation area 21 is provided with an inlet 24, the end point of the second microfluidic channel 23 far away from the operation area 21 is provided with an outlet 25, wherein the inlet 24 is used for connecting a syringe, and the outlet 25 is used for connecting a waste liquid pool.
It should be noted that the particles may be input into the first microfluidic channel 22 through the syringe, and then flow to the waste liquid pool through the second microfluidic channel 23 after passing through the operation area 21, and the first microfluidic channel 22 and the second microfluidic channel 23 are configured as a corrugated channel, which may reduce the influence of the fluid flow at the inlet 24 on the movement of the particles in the square operation space.
In this embodiment, the material of the intermediate layer 2 may be PDMS.
The PDMS is polydimethylsiloxane, a hydrophobic organic silicon material, has heat resistance, cold resistance, small viscosity change along with temperature, water resistance, small surface tension and thermal conductivity, has a thermal conductivity coefficient of 0.134-0.159W/(m.K), and has light transmittance of 100%, and the dimethicone is nontoxic, odorless, physiologically inert and good in chemical stability. The electric insulation, weather resistance and hydrophobicity are good, the anti-shearing capacity is high, the electric insulation, weather resistance and hydrophobicity can be used for a long time at minus 50 ℃ to 200 ℃, in other embodiments, other materials can be adopted, and the scheme is not particularly limited, but the scheme is within the protection scope of the invention.
In the present embodiment, the first substrate 1 and the second substrate 3 may be glass substrates.
Electrodes and contacts may be disposed on the upper surface of the first substrate 1 and the lower surface of the second substrate 3 by photolithography, wherein the first edge electrode 11 and the second edge electrode 31 may be made of ITO electrodes.
In this embodiment, the first substrate 1, the intermediate layer 2 and the second substrate 3 may be assembled together by a plasma bonding method, and the three-layer structure may be clamped by a clamp and observed under a microscope.
In the present embodiment, a projection of each of the first contacts 12 perpendicular to the operating region 21 and each of the second contacts 32 are not in contact with each other.
It should be noted that, in this embodiment, the number of the first contacts 12 may be 5, and the number of the second contacts 32 may be 4, but is not limited thereto, a squared figure is formed in the operation area 21, wherein a projection of each first contact 12 in a direction perpendicular to the operation area 21 is not in contact with each second contact 32. Precise control of the electric field around the particles can be achieved.
Referring to fig. 7, a second embodiment of the present invention provides an array type micro operating system, which includes a controller 41, a signal generator 43, an electron microscope 45, an industrial camera 41, and an upper computer 42;
the output of signal generator 43 with the input electrical connection of controller 41, the output of controller 41 is with a plurality of first edge electrode 11, a plurality of second edge electrode 31 electrical connection, electron microscope 45 disposes the top of operation area 21, electron microscope 45's output with the input electrical connection of industry camera 41, industry camera 41's output with the input electrical connection of host computer 42, the output of host computer 42 with the input electrical connection of controller 41.
It should be noted that the electron microscope 45 is configured to collect controlled ions on the operation area 21, and may collect and determine an object to be observed, and collect an image to the upper computer 42 through the industrial camera 41, where the industrial camera 41 may be a CCD camera or another type of industrial camera 41, the upper computer 42 may be a PC terminal, and the upper computer 42 may send the position in the image to the controller 41 after recognizing the position, where the signal generator 43 is configured to generate a generation signal, and generate different levels to the first edge electrode 11 or the second edge electrode 31 through the controller 41.
In this embodiment, the chip model of the controller 41 may be STM32F 103.
It should be noted that, in other embodiments, the controller 41 in the series C51 may also be used, which is not limited herein, but these schemes are all within the protection scope of the present invention.
A third embodiment of the present invention provides a control method as described above, including:
receiving current position information of the particles on the operation area 21 and target position information of the particles, wherein the current position information is acquired by the electron microscope 45 and the industrial camera 41 and then sent to the upper computer 42;
generating a control signal based on the current position information and the target position information, wherein the control signal is used for switching on and off the first edge electrode 11 or the second edge electrode 31 so as to enable the particles to move to the target position.
Referring to fig. 8, for example, the upper and lower electrodes are respectively denoted by a and B, and the dielectric particles are driven from S point to T point in the figure, where S point is the current position and T point is the target position, which can be realized by the following electrode combination sequence: a1+ B4, B2+ B4+ A5, A5+ A7+ B8, B6+ B8+ A9.
Based on the array type micro-operation chip, the operation system and the operation method provided by the invention, the operation area 21, the first micro-fluidic channel 22 and the second micro-fluidic channel 23 are arranged on the middle layer 2, wherein, the particles flow to the operation area 21 from the first micro-fluidic channel 22, then from the second micro-fluidic channel 23, the plurality of first contacts 12 arranged on the first substrate 1 are contacted with the first surface of the operation area 21, the plurality of second contacts 32 arranged on the second substrate 3 are contacted with the second surface of the operation area 21, and then the alternating levels are respectively provided for the contacts through the first edge electrode 11 and the second edge electrode 31, so that the particles on the operation area 21 can move from the current position to the target position along with the alternating levels. The problems that in the prior art, the operation force is weak and the controllable area is small for micron-scale particles in an electric field are solved.
The above is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above-mentioned embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention.

Claims (8)

1. An array type micro-operation chip, comprising: a first substrate, an intermediate layer, and a second substrate;
wherein an upper surface of the first substrate is in contact with a first surface of the intermediate layer and a lower surface of the second substrate is in contact with a second surface of the intermediate layer;
the central part of the middle layer is provided with an operation area, a first microfluidic channel arranged on the first side of the operation area and a second microfluidic channel arranged on the second side of the operation area;
a plurality of first contacts are configured at the central part of the upper surface of the first substrate, the first contacts are electrically connected to a plurality of first edge electrodes at the end part of the first substrate, and the first edge electrodes are used for being electrically connected with an output end of a controller;
a plurality of second contacts are arranged at the central part of the lower surface of the second substrate, the plurality of first contacts are electrically connected to a plurality of second edge electrodes at the end part of the second substrate, and the second edge electrodes are used for being electrically connected with an output end of a controller;
wherein a plurality of the first contacts are in contact with a first surface of the operational area and a plurality of the second contacts are in contact with a second surface of the operational area.
2. The arrayed micro-manipulation chip of claim 1, wherein the first and second microfluidic channels are corrugated channels.
The end point of the first microfluidic channel, which is far away from the operation area, is provided with an inlet, and the end point of the second microfluidic channel, which is far away from the operation area, is provided with an outlet, wherein the inlet is used for connecting an injector, and the outlet is used for connecting a waste liquid pool.
3. The array-type micro-manipulator chip of claim 1, wherein the intermediate layer is made of PDMS.
4. The arrayed micro manipulation chip of claim 1, wherein the first substrate and the second substrate are glass substrates.
5. An arrayed micro-manipulator chip according to claim 1, wherein each of the first contacts does not contact each of the second contacts in a projection perpendicular to the manipulation region.
6. An array type micro-operation system is characterized by comprising a controller, a signal generator, an electron microscope, an industrial camera and an upper computer;
the output of signal generator with the input electrical connection of controller, the output of controller is with a plurality of first edge electrode, a plurality of second edge electrode electrical connection, the electron microscope configuration is in operating area's top, the electron microscope's output with the input electrical connection of industry camera, the output of industry camera with the input electrical connection of host computer, the output of host computer with the input electrical connection of controller.
7. An arrayed micro-operating system according to claim 6, wherein the controller has a chip model number STM32F 103.
8. A control method according to claim 6, comprising:
receiving current position information of particles on an operation area and target position information of the particles, wherein the current position information is collected by the electron microscope and the industrial camera and then sent to the upper computer;
generating a control signal based on the current position information and the target position information, wherein the control signal is used for switching on and off a first edge electrode or a second edge electrode to enable the particles to move to the target position.
CN202111444729.4A 2021-11-30 2021-11-30 Array type micro-operation chip, operation system and operation method Pending CN113967490A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090308473A1 (en) * 2008-06-16 2009-12-17 Sony Corporation Micro-fluidic chip and flow sending method in micro-fluidic chip
CN107118938A (en) * 2017-04-07 2017-09-01 中北大学 The unicellular arrangement of fluid enhancing dielectrophoresis and control chip and preparation method thereof
CN110860321A (en) * 2019-12-11 2020-03-06 河北工业大学 Controllable micro-scale bubble chip and acoustic flow control particle separation method and system
CN113201435A (en) * 2020-01-15 2021-08-03 佛山奥素博新科技有限公司 Digital microfluidic system

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090308473A1 (en) * 2008-06-16 2009-12-17 Sony Corporation Micro-fluidic chip and flow sending method in micro-fluidic chip
CN107118938A (en) * 2017-04-07 2017-09-01 中北大学 The unicellular arrangement of fluid enhancing dielectrophoresis and control chip and preparation method thereof
CN110860321A (en) * 2019-12-11 2020-03-06 河北工业大学 Controllable micro-scale bubble chip and acoustic flow control particle separation method and system
CN113201435A (en) * 2020-01-15 2021-08-03 佛山奥素博新科技有限公司 Digital microfluidic system

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Application publication date: 20220125