CN110653011A - Reusable double-layer digital microfluidic chip based on hydrophobic film and rapid preparation method - Google Patents

Reusable double-layer digital microfluidic chip based on hydrophobic film and rapid preparation method Download PDF

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CN110653011A
CN110653011A CN201910939704.8A CN201910939704A CN110653011A CN 110653011 A CN110653011 A CN 110653011A CN 201910939704 A CN201910939704 A CN 201910939704A CN 110653011 A CN110653011 A CN 110653011A
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layer
electrode
hydrophobic
polar plate
array
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应义斌
王振
叶尊忠
吴翠
应圣纳
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Zhejiang University ZJU
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Zhejiang University ZJU
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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
    • B01L3/502707Containers 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 manufacture of the container or its components
    • 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
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • B01L2300/161Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165Specific details about hydrophobic, oleophobic surfaces
    • 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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  • Dispersion Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Clinical Laboratory Science (AREA)
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Abstract

The invention discloses a reusable double-layer digital microfluidic chip based on a hydrophobic film and a rapid preparation method thereof. The upper-layer polar plate comprises an upper hydrophobic layer, a substrate and a conducting layer; the lower electrode plate mainly comprises an electrode layer and a dielectric hydrophobic composite layer, the electrode layer comprises an electrode array layer and a large electrode layer, the large electrode layer is arranged in the liquid storage area, and the electrode array layer is arranged in the motion area; the large electrode layer comprises a large electrode and a small electrode; the electrode array layer comprises a printed circuit board substrate and an electrode array; circuit board through holes are formed in the middle of each driving electrode unit and the small and large electrodes, and bonding pads are arranged around the through holes; reagent droplets are arranged between the lower layer polar plate and the upper layer polar plate. The process provided by the invention can greatly reduce the preparation cost of the digital microfluidic chip, avoid the possibility of cross infection caused by biological reagent adsorbed on the surface of the material, and improve the flexibility and stability of the microfluidic.

Description

Reusable double-layer digital microfluidic chip based on hydrophobic film and rapid preparation method
Technical Field
The invention relates to a micro-fluidic chip and a preparation method thereof in the micro-fluidic field, in particular to a reusable double-layer digital micro-fluidic chip based on a hydrophobic film and a rapid preparation method thereof.
Background
At present, when related biochemical experiments are involved in the fields of drug research and development, disease detection, gene detection and the like, experimenters are required to use tools such as pipette guns, kits, test tubes and the like to carry out experiments. The use of a large number of repeated steps and test reagents results in a great waste of test resources. Different channels are designed on a chip by the micro-fluidic technology to realize the mixed reaction function of liquid, reaction and detection steps can be concentrated on one chip by combining a certain detection means, the volume of reaction liquid drops is reduced to nano-liter or even pico-liter level, the reaction liquid drops are controlled by controlling the electric field change of the chip to independently complete the experiment, the experiment steps, the reagent consumption and the labor input are greatly reduced, and the method is an effective means for reducing the experiment cost.
The digital microfluidic technology can independently control liquid drops by using an electric field, and is different from the traditional continuous microfluidic technology which uses a micro-valve micropump to control liquid or air pressure to realize reaction liquid conveying. The digital microfluidic chip can realize the transportation, fusion, division and distribution of liquid drops, and can realize the automation of complex biochemical tests by controlling the electric field of the electrode array and combining with a proper detection means.
The traditional preparation method of the digital microfluidic chip adopts an MEMS (micro electro mechanical systems) manufacturing Process, which has strict requirements on preparation environment, expensive price of required equipment and complex manufacturing Process, and is not suitable for mass production and application. In addition, the digital microfluidic chip prepared by the traditional MEMS process has some problems in chip recycling. In the experimental process, the dielectric layer is easy to break down or biological pollution occurs to cause that the chip can not be used continuously, the experimental cost is further improved, and the subsequent practical application is not facilitated.
The preparation process of the existing digital microfluidic chip needs to realize the preparation of electrodes by a photoetching technology, and a matched instrument and a super clean room are needed, so that the preparation condition of the chip is improved. The traditional chip respectively comprises a dielectric layer and a hydrophobic layer, wherein each layer is prepared by a spin coating process, the steps are complex, and if the thickness of an electrode is too large, the dielectric layer and the hydrophobic layer can form a gully, which affects the stability of droplet movement.
Disclosure of Invention
Aiming at solving the problems in the background art and aiming at the defects of complex preparation method, high preparation cost and the like of the conventional digital microfluidic chip, the invention provides a reusable double-layer digital microfluidic chip based on a hydrophobic film and a rapid preparation method thereof. The chip takes the hydrophobic film as the dielectric layer and the hydrophobic layer of the digital microfluidic chip at the same time, has the characteristics of reusability and quick preparation, and effectively reduces the manufacturing cost and the experimental cost of the digital microfluidic chip.
The technical scheme of the invention is as follows:
a reusable double-layer digital microfluidic chip based on a hydrophobic film comprises:
the chip comprises a lower-layer polar plate and an upper-layer polar plate, wherein the upper-layer polar plate is mainly formed by sequentially laminating an upper-layer polar plate hydrophobic layer, an upper-layer polar plate conductive layer and an upper-layer polar plate substrate from bottom to top; the lower electrode plate mainly comprises an electrode layer and a dielectric hydrophobic composite layer, wherein the electrode layer is formed by an electrode array layer and a large electrode layer together, the dielectric hydrophobic composite layer is arranged on the electrode layer, one side of the dielectric hydrophobic composite layer is used as a liquid storage area, the large electrode layer is arranged in the liquid storage area, the other side of the dielectric hydrophobic composite layer is used as a motion area, and the electrode array layer is arranged in the motion area; the large electrode layer comprises a large electrode and at least one small electrode positioned around the large electrode; the electrode array layer comprises a printed circuit board substrate and an electrode array arranged on the upper surface of the printed circuit board substrate, the electrode array is formed by arranging a plurality of driving electrode unit arrays, and an electrode gap is formed between every two adjacent driving electrode units; the shape and the size of the small electrode of the large electrode layer and the driving electrode unit in the electrode array layer are kept consistent, the shape of the large electrode layer and the driving electrode unit in the electrode array layer are kept consistent, but the size of the large electrode layer is larger than that of the driving electrode unit in the electrode array layer; circuit board through holes are formed in the middle of each driving electrode unit, the small electrodes and the large electrodes, and after the circuit board through holes penetrate through the printed circuit board substrate, bonding pads are arranged on the lower surface of the printed circuit board substrate around the circuit board through holes; the dielectric hydrophobic composite layer is completely and completely attached to the upper surface of the lower layer polar plate; reagent droplets are arranged between the lower layer polar plate and the upper layer polar plate, and each driving electrode unit of the electrode array of the lower layer polar plate and the small electrode and the large electrode of the upper layer polar plate are led out through the circuit board through holes and connected to an external voltage control end.
The digital microfluidic chip provided by the invention has a double-layer structure, namely the chip is composed of two polar plates, and liquid drops move between the two polar plates.
The driving electrode units in the electrode array layer are square electrode plates, and the electrode array is formed by arranging a plurality of square electrode plates in a square array.
The driving electrode units in the electrode array layer are square electrode plates with four edges replaced by straight edges of a fold line shape or a wave shape, and the electrode array is formed by arranging a plurality of square electrode plates in a square array.
The driving electrode unit in the electrode array layer is a triangular electrode slice with three linear edges replacing fold line edges or wave-shaped edges, and the electrode array is formed by arranging a plurality of triangular electrode slices in a triangular array.
The driving electrode units in the electrode array layer are hexagonal electrode plates with six straight edges replacing fold line edges or wave-shaped edges, and the electrode array is formed by arranging a plurality of hexagonal electrode plates in a honeycomb array.
The dielectric hydrophobic composite layer is a Polytetrafluoroethylene (PTFE) film or a perfluoroethylene propylene copolymer (FEP) film and the like.
And a layer of oil film is coated between the dielectric hydrophobic composite layer and the electrode array layer and between the lower pole plate and the upper pole plate, and the oil film material is selected from silicone oil, paraffin oil or edible oil and the like. The oil film is arranged between the dielectric hydrophobic composite layer and the electrode array layer and used for ensuring the stability of the joint between the two layers; the oil film between the lower pole plate and the upper pole plate fills the whole gap to reduce the evaporation of liquid drops.
In the large electrode layer, the hydrophobic layer of the upper electrode plate adopts fluoride paint with hydrophobic characteristics such as Teflon and Cytop, the substrate of the upper electrode plate adopts glass or PET, and the conductive layer of the upper electrode plate adopts Indium Tin Oxide (ITO).
Secondly, a preparation method of the single-layer digital microfluidic chip is characterized by comprising the following steps:
the preparation method comprises the following steps:
1) the electrode array layer is prepared by an industrial printed circuit board preparation method, for example, a PCB preparation method, a layer of grease such as silicone oil, paraffin oil and the like is coated on the surface of the electrode array layer to form an oil film, a single-layer hydrophobic material prepared in advance is flatly attached to the upper surface of the electrode array layer by an attaching method to form a dielectric hydrophobic composite layer, bubbles between the two layers are removed through the action between the oil film and the surface of the electrode array layer and between the oil film and the hydrophobic material, and the close attachment between the two layers can be ensured through the oil film. Therefore, the method for rapidly preparing the single-layer digital microfluidic chip is very simple and effectively realized, and the lower-layer polar plate is prepared and obtained;
2) preparing an upper-layer polar plate conducting layer which is completely covered on the upper surface of an upper-layer polar plate substrate by adopting an industrial printed circuit board preparation method, and then flatly attaching a single-layer hydrophobic material which is prepared in advance to the lower surface of the upper-layer polar plate substrate to form an upper-layer polar plate hydrophobic layer, thereby preparing and obtaining an upper-layer polar plate;
3) and finally, arranging the upper reagent liquid drop between the lower polar plate and the upper polar plate.
In the preparation method, the lower-layer polar plate is directly attached to the electrode array layer by adopting a single-layer hydrophobic material, the complex preparation steps of forming the dielectric layer and the hydrophobic layer on the electrode array layer through spin coating for multiple times in the prior art are replaced, the problem that the traditional digital microfluidic chip cannot be reused after the dielectric layer is broken down is solved, the difficulty of preparing the digital microfluidic chip and the requirements on equipment can be greatly reduced through the preparation method, the cost of the chip is reduced, the stability of the performance of the chip is ensured, and the preparation method has the advantages of low cost, high preparation speed and suitability for batch production.
Compared with the traditional MEMS processing digital microfluidic chip, the lower layer polar plate does not need a photoetching machine, a sputtering film plating machine and other instruments, the preparation cost of the digital microfluidic chip is reduced, and the hydrophobic material can simultaneously play the functions of the dielectric layer and the hydrophobic layer of the traditional digital microfluidic chip.
And a layer of oil film is coated between the dielectric hydrophobic composite layer and the electrode array layer, and the oil film material is selected from silicone oil, paraffin oil or edible oil and the like, so that the stability of the joint between the two layers is ensured.
And a layer of oil film is coated between the lower-layer polar plate and the upper-layer polar plate, and the oil film material is selected from silicone oil, paraffin oil or edible oil and the like to fill the whole gap and reduce the evaporation of liquid drops.
The invention has the beneficial effects that:
compared with the traditional MEMS processing technology, the preparation method of the digital microfluidic chip provided by the invention does not need strict ultra-clean room environment, sputtering coating equipment and other equipment. The dielectric hydrophobic composite layer of the digital microfluidic chip is formed by attaching the existing hydrophobic film, and complex operations such as spin coating, meteorological deposition and the like are not needed. The steps of the chip are greatly simplified, and the manufacturing cost is reduced. The prepared digital microfluidic chip can be repeatedly used, and the experiment cost can be further reduced.
According to the invention, the micro-fluidic chip can be controlled more flexibly under the structural design and manufacturing process of the micro-fluidic chip, so that the selectable path of the movement of the reagent droplet is more direct, simple and effective, the smoothness of the surface movement of the reagent droplet can be improved, and the stability of the movement of the reagent droplet can be obviously improved when the reagent droplet moves on the smooth dielectric hydrophobic composite layer.
Meanwhile, the invention can lower and simplify the cost of replacing the unit when the voltage breaks down the film, and realize low-cost reuse.
In addition, the invention is provided with a storage area, which can realize the liquid drop distribution operation in the liquid drop control, namely the step of distributing a plurality of sub-liquid drops by mother liquid drop. The double-layer digital microfluidic structure can realize droplet transportation, droplet splitting, droplet fusion and droplet distribution of droplet control, and can complete more complex experiments.
Drawings
FIG. 1 is a cross-sectional view of a dual-layer digital microfluidic chip according to the present invention;
FIG. 2 is a top view of a dual-layer digital microfluidic chip according to the present invention;
FIG. 3 is a partial structure diagram of an upper plate of the double-layer digital microfluidic chip according to the present invention;
FIG. 4 is a structural diagram of a driving electrode unit formed by a fold line-shaped edge; in FIG. 3, from (a) to (c) are respectively a regular triangle, a square and a regular hexagon composed of zigzag lines;
FIG. 5 is a view of a driving electrode unit constructed with wavy edges; in fig. 5, from (a) to (c) are respectively a regular triangle, a square and a regular hexagon composed of wavy lines.
Fig. 6 is an electrode array composed of regular triangles, squares and regular hexagons of the zigzag edge-driven electrode unit.
Fig. 7 is an electrode array consisting of regular triangles, squares and hexagons of the wave-shaped edge driving electrode unit.
In the figure: the circuit board comprises a circuit board through hole 1, a bonding pad 2, a printed circuit board substrate 3, a driving electrode unit 4, a lower-layer polar plate 5, an upper-layer polar plate hydrophobic layer 6, an upper-layer polar plate substrate 7, an upper-layer polar plate conductive layer 8, a reagent droplet 9, a dielectric hydrophobic composite layer 10, an electrode array 11, a large electrode 12, an upper-layer polar plate 13, a small electrode 14 and a mother droplet 15.
Detailed Description
The present invention will be further described with reference to the drawings attached to the specification, but the present invention is not limited to the following examples.
As shown in fig. 1, the composite plate comprises a lower-layer polar plate 5 and an upper-layer polar plate 13, and as shown in fig. 3, the upper-layer polar plate 13 is mainly formed by sequentially laminating an upper-layer polar plate hydrophobic layer 6, an upper-layer polar plate substrate 7 and an upper-layer polar plate conductive layer 8 from bottom to top; the lower electrode plate 5 mainly comprises an electrode layer and a dielectric hydrophobic composite layer 10, the electrode layer is composed of an electrode array layer and a large electrode layer, the dielectric hydrophobic composite layer 10 is arranged on the electrode layer, one side of the dielectric hydrophobic composite layer 10 serves as a liquid storage area, the large electrode layer is arranged in the liquid storage area, the other side of the dielectric hydrophobic composite layer serves as a movement area, and the electrode array layer is arranged in the movement area.
As shown in FIG. 2, the reservoir region is arranged with a large electrode layer comprising one large electrode 12 and at least one small electrode 14 located about the circumference of the large electrode 12.
As shown in fig. 2, the motion area is provided with an electrode array layer, the electrode array layer comprises a printed circuit board substrate 3 and an electrode array 11 arranged on the upper surface of the printed circuit board substrate 3, the electrode array 11 is formed by arranging a plurality of driving electrode units 4 in an array manner, and an electrode gap is formed between every two adjacent driving electrode units 4.
In the liquid storage area and the movement area, the shape and the size of the small electrode of the large electrode layer and the driving electrode unit 4 in the electrode array layer are kept consistent, the shape of the large electrode 12 of the large electrode layer and the shape of the driving electrode unit 4 in the electrode array layer are kept consistent, but the size of the large electrode 12 of the large electrode layer is larger than that of the driving electrode unit 4 in the electrode array layer; a circuit board through hole 1 is formed in the middle of each driving electrode unit 4, the small electrode and the large electrode 12, after the circuit board through hole 1 penetrates through the printed circuit board substrate 3, a bonding pad 2 is arranged on the lower surface of the printed circuit board substrate 3 around the circuit board through hole 1, and the driving electrode units 4, the small electrodes and the large electrode 12 are connected to the through hole bonding pads 2 below the printed circuit board substrate 3 through the circuit board through holes 1; the dielectric hydrophobic composite layer 10 is attached entirely over the lower plate 5.
Reagent droplets 9 are arranged between the lower-layer polar plate 5 and the upper-layer polar plate 13, namely a movement area of the reagent droplets 9 is arranged between the hydrophobic layer 6 of the upper-layer polar plate and the dielectric hydrophobic composite layer 10, each driving electrode unit 4 of the electrode array 11 of the lower-layer polar plate 5 and the small electrode and the large electrode 13 of the upper-layer polar plate 13 are led out through the circuit board through hole 1 and connected to an external voltage control end, and the upper-layer polar plate conducting layer 8 is led out to the voltage control end through a conducting adhesive tape at one side.
The liquid storage area is used for storing reagent liquid drops 9 with larger volume, the large electrode 12 and the small electrode 14 nearby drive the electrode unit to form a liquid drop distribution area, and the process of distributing the mother liquid drops 15 into the sub liquid drops is realized; the motion area is an electrode array formed by the driving electrode units 4 and is used as a liquid drop motion area which is a main motion area of liquid drops, and the operations of conveying, fusing and splitting of the liquid drops are realized. The driving electrode units are arranged in an array according to the principle that the corresponding edges are parallel, and an electrode gap is formed between every two adjacent driving electrode units 4.
The large electrode 12 and the surrounding area thereof are used as a liquid storage area of the reagent liquid drop 9, the larger mother liquid drop stays in the range of the liquid storage area, different/same voltages are applied at different real-time moments through the control voltage control end to drive the mother liquid drop to separate a plurality of smaller sub liquid drops, the sub liquid drops move to the motion area, different/same voltages are applied to each driving electrode unit 4 of the motion area through the control voltage end at different real-time moments to drive the plurality of sub liquid drops to rapidly move on the dielectric hydrophobic composite layer 10, and the motions of separation, fusion and the like can be realized, so that the work of the microfluidic chip is realized.
The reagent liquid drops 9 adopt a KCl solution with the concentration of 0.2mol/L, and the volume of each liquid drop is 5 mu L of liquid.
A plurality of reagent droplets 9 may be disposed between the upper plate hydrophobic layer 6 and the dielectric hydrophobic composite layer 10. In the case that the reagent droplet 9 may be a plurality of droplets composed of a plurality of components, a plurality of reagents may be selected as different droplets to participate in the experiment according to the experiment requirement. The plurality of reagent droplets 9 may each control the movement of the droplet by applying an electric field across electrodes in the vicinity of the droplet. After an electric field is applied to the electrode unit 22 near the reagent droplet 9, the droplet moves toward the electrode unit 22 under the action of the electric field, reaches the position right above the electrode 22, and stops, that is, the transporting step in the droplet manipulating step. In this way, the two liquid drops can be controlled to move to the same electrode to complete the fusion step. After the electric field is applied to the driving electrode units 21, 22, 23 in the vicinity of the reagent droplet 9 at the same time, the step of splitting the droplet, i.e. splitting one droplet into two droplets, can be performed by turning off the electric field of the driving unit 22. An electric field is applied to the driving electrode units 24 and 23 in sequence, the mother liquid drops 20 partially move towards the driving electrode units 23 and 24 under the action of the electric field, the mother liquid drops 20 partially cover the electrodes 23 and 23, and then the electric field of the electrode 24 is closed, so that partial volume of the mother liquid drops 20 can be separated from the body of the mother liquid drops 20, and the distribution step in the drop control is realized. The design of complex experimental protocols can be achieved through the above interworking of droplet delivery, fusion, fragmentation and dispensing steps.
The electrode array layer adopts an industrial printed circuit board process; the dielectric hydrophobic composite layer 10 is attached to the electrode array layer by an attachment method.
In specific implementation, the driving electrode units 4 in the electrode array layer may be in different shapes and forms, and arranged in different array manners:
as shown in fig. 4(b), 5(b), 6(b) and 7(b), the driving electrode unit 4 in the electrode array layer is a square electrode sheet, and the electrode array 11 is formed by arranging a plurality of square electrode sheets in a square array.
The driving electrode unit 4 in the electrode array layer is a square electrode plate with four straight edges replacing a zigzag edge or a wavy edge, and the electrode array 11 is formed by arranging a plurality of square electrode plates in a square array.
As shown in fig. 4(a), 5(a), 6(a) and 7(a), the driving electrode unit 4 in the electrode array layer is a triangular electrode piece in which the straight edges of three sides are replaced by the zigzag edges or the wavy edges, and the electrode array 11 is formed by arranging a plurality of triangular electrode pieces in a triangular array.
As shown in fig. 4(c), 5(c), 6(c) and 7(c), the driving electrode units 4 in the electrode array layer are hexagonal linear edges each having six sides instead of a hexagonal electrode piece having a zigzag edge or a wavy edge, and the electrode array 11 is formed by arranging a plurality of hexagonal electrode pieces in a honeycomb array.
The shape of the electrode array is designed into different arrangement rules according to the needs. The electrode array 5 as in fig. 1 and 2 consists of a 3 x 3 square array of electrodes. The arrangement of the electrodes is not limited to the 3 × 3 structure.
As shown in fig. 4 and 5, respectively, the dogleg-shaped edge is formed by a continuous crease line. The wavy edge is constituted by a continuous wavy line.
When the control liquid drops are used as driving electrode units on the triangular electrode slice, the moving directions of the liquid drops are in three directions on a plane; when the control liquid drop is in the hexagonal electrode plate as the driving electrode unit, the moving direction of the liquid drop has six directions on the plane. In experiments, the degree of freedom of the liquid drop during movement is related to the shape of the formed electrode array, and the more the number of the polygonal sides forming the electrode shape is, the more the direction selected by the liquid drop movement is, so that the more complicated movement path of the liquid drop can be controlled.
The pitch range between adjacent driving electrode units 7 is 50 μm or more, and specifically may be 50 μm to 150 μm. The side length of the driving electrode unit 7 ranges from 0.5mm to 10 mm.
The dielectric hydrophobic composite layer 6 is a material with certain hydrophobicity, and specifically is a polytetrafluoroethylene PTFE film or a perfluoroethylene propylene copolymer FEP film or the like. The thickness of the dielectric hydrophobic composite layer 6 ranges from 0.5 μm to 100. mu.m.
And a layer of oil film is further coated on the dielectric hydrophobic composite layer 6, and the oil film material is selected from silicone oil, paraffin oil or edible oil and the like. The experiment duration is longer, silicone oil, paraffin oil and the like are filled between the upper pole plate and the lower pole plate, and the reagent liquid drop 9 and the large liquid drop 20 are coated in the silicone oil, the paraffin oil and the like, so that the evaporation amount of the liquid drops in the experiment process is reduced, and the stability of the liquid drops in the movement process is improved.
In the large electrode layer, the upper-layer polar plate hydrophobic layer 6 is made of materials such as Teflon and Cytop, the fluoride of which has hydrophobic characteristics, the upper-layer polar plate substrate 7 is made of glass or PET, the upper-layer polar plate substrate 7 has rigidity, and the upper-layer polar plate conductive layer 8 is made of Indium Tin Oxide (ITO).
The specific embodiment and the implementation working process of the invention are as follows:
1) preparing the lower electrode plate 5
Firstly, an electrode array layer and a large electrode layer are prepared and obtained by adopting an industrial printed circuit board preparation method.
The large electrode layer is arranged in a liquid storage area below the dielectric hydrophobic composite layer 10, the electrode array layer is arranged in a motion area below the dielectric hydrophobic composite layer 10, the electrode array layer is formed by arranging driving electrode units 4 of square electrode plates with the same shape and size in a square array mode, and the driving electrode units are arranged in parallel according to corresponding edges and are evenly distributed according to the principle that the distances between the edges are equal.
Then, the dielectric hydrophobic material film is made of Polytetrafluoroethylene (PTFE) film or perfluoroethylene propylene (FEP) film and the like, the prepared dielectric hydrophobic material film is attached to the surface of the electrode array layer formed by the driving electrode unit, air on the surfaces of the film and the electrode array layer is removed by utilizing silicon oil, edible oil and the like, and meanwhile, the film can be stably attached to the surface of the electrode array layer.
After the dielectric hydrophobic composite layer is attached, a layer of oil film of silicone oil is added to the surface of the dielectric hydrophobic composite layer, so that the voltage applied in an experiment can be reduced.
2) Preparation of the upper electrode plate 13
The upper substrate is generally made of a transparent conductive material, and a common material is ITO. The substrate adopts the existing ITO glass material as the combination body of the upper-layer polar plate substrate 7 and the conducting layer 8, hydrophobic material Teflon or Cytop is coated on the surface in a spin coating mode, the spin coating speed is 2000rmp, the surface with the hydrophobic characteristic is obtained by drying at the temperature of 80 ℃, and the upper-layer polar plate is manufactured.
The substrate 7 and the conducting layer 8 are made of ITO glass and ITO-PET, and a layer of dense hydrophobic material is coated on one side of ITO in a spin mode to complete the manufacturing of the upper-layer polar plate.
When the dielectric hydrophobic composite layer 6 is subjected to an electric breakdown phenomenon or other experiments, the dielectric hydrophobic composite layer 6 on the surface can be taken down and a layer of film is attached again, so that the multiplexing of the digital microfluidic chip can be realized, the possibility of cross infection caused by biological reagents adsorbed on the surface of the material can be avoided by the method, and the experiment cost of the digital microfluidic chip can be greatly reduced.
The digital microfluidic chip and the preparation method thereof provided by the invention have great advantages in preparation cost and experiment cost, and are a new idea for putting the digital microfluidic chip into practical application.

Claims (10)

1. A can multiplexing double-deck digital micro-fluidic chip based on hydrophobic film which characterized in that: the device comprises a lower-layer polar plate (5) and an upper-layer polar plate (13), wherein the upper-layer polar plate (13) is mainly formed by sequentially laminating an upper-layer polar plate hydrophobic layer (6), an upper-layer polar plate conductive layer (8) and an upper-layer polar plate substrate (7) from bottom to top; the lower-layer polar plate (5) mainly comprises an electrode layer and a dielectric hydrophobic composite layer (10), wherein the electrode layer is formed by an electrode array layer and a large electrode layer together, the dielectric hydrophobic composite layer (10) is arranged on the electrode layer, one side of the dielectric hydrophobic composite layer (10) is used as a liquid storage area, the large electrode layer is arranged in the liquid storage area, the other side of the dielectric hydrophobic composite layer is used as a motion area, and the electrode array layer is arranged in the motion area; the large electrode layer comprises a large electrode (12) and at least one small electrode positioned around the large electrode (12); the electrode array layer comprises a printed circuit board substrate (3) and an electrode array (11) arranged on the upper surface of the printed circuit board substrate (3), the electrode array (11) is formed by arranging a plurality of driving electrode units (4) in an array mode, and an electrode gap is formed between every two adjacent driving electrode units (4); the shape and the size of the small electrode of the large electrode layer and the driving electrode unit (4) in the electrode array layer are consistent, the shape of the large electrode (12) of the large electrode layer and the driving electrode unit (4) in the electrode array layer are consistent, but the size of the large electrode (12) of the large electrode layer is larger than the size of the driving electrode unit (4) in the electrode array layer; a circuit board through hole (1) is formed in the middle of each driving electrode unit (4) and the small electrode and the large electrode (12), and after the circuit board through hole (1) penetrates through the printed circuit board substrate (3), a bonding pad (2) is arranged on the lower surface of the printed circuit board substrate (3) around the circuit board through hole (1); the dielectric hydrophobic composite layer (10) is completely and completely attached to the upper surface of the lower pole plate (5); reagent liquid drops (9) are arranged between the lower layer polar plate (5) and the upper layer polar plate (13), and each driving electrode unit (4) of the electrode array (11) of the lower layer polar plate (5) and the small electrode and the large electrode (13) of the upper layer polar plate (13) are led out through the circuit board through hole (1) to be connected to an external voltage control end.
2. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: the driving electrode unit (4) in the electrode array layer is a square electrode plate, and the electrode array (11) is formed by arranging a plurality of square electrode plates in a square array.
3. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: the driving electrode unit (4) in the electrode array layer is a square electrode plate with four straight edges replacing a zigzag edge or a wavy edge, and the electrode array (11) is formed by arranging a plurality of square electrode plates in a square array.
4. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: the driving electrode unit (4) in the electrode array layer is a triangular electrode slice with three linear edges replacing a fold line-shaped edge or a wave-shaped edge, and the electrode array (11) is formed by arranging a plurality of triangular electrode slices in a triangular array.
5. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: the driving electrode units (4) in the electrode array layer are hexagonal electrode plates with six straight edges replacing fold line edges or wave edges, and the electrode array (11) is formed by arranging a plurality of hexagonal electrode plates in a honeycomb array.
6. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: the dielectric hydrophobic composite layer (6) is a Polytetrafluoroethylene (PTFE) film or a perfluoroethylene propylene copolymer (FEP) film and the like.
7. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: a layer of oil film is coated between the dielectric hydrophobic composite layer (6) and the electrode array layer and between the lower layer polar plate (5) and the upper layer polar plate (13), and the oil film material is selected from silicone oil, paraffin oil or edible oil.
8. The reusable double-layer digital microfluidic chip based on the hydrophobic film according to claim 1, wherein: in the large electrode layer, the upper electrode plate hydrophobic layer (6) is made of fluoride paint with hydrophobic characteristics such as Teflon and Cytop, the upper electrode plate substrate (7) is made of glass or PET, and the upper electrode plate conducting layer (8) is made of Indium Tin Oxide (ITO).
9. A method for preparing a single-layer digital microfluidic chip according to any one of claims 1 to 8, comprising:
the preparation method comprises the following steps:
1) an electrode array layer is prepared by adopting an industrial printed circuit board preparation method, a layer of grease such as silicone oil, paraffin oil and the like is coated on the surface of the electrode array layer (4) to form an oil film, a single-layer oil film hydrophobic material prepared in advance is flatly attached to the upper surface of the electrode array layer by an attaching method to form a dielectric hydrophobic composite layer (6), bubbles between the two layers are removed through the action between the oil film and the surface of the electrode array layer and between the two layers and the hydrophobic material, and the two layers are tightly attached through the oil film, so that a lower-layer polar plate (5) is;
2) preparing an upper-layer polar plate conducting layer (8) which is completely covered on the upper surface of an upper-layer polar plate substrate (7) by adopting an industrial printed circuit board preparation method, and then flatly attaching a single-layer hydrophobic material which is prepared in advance to the lower surface of the upper-layer polar plate substrate (7) to form an upper-layer polar plate hydrophobic layer (6), thereby preparing and obtaining an upper-layer polar plate (13);
3) finally, an upper reagent droplet (9) is arranged between the lower plate (5) and the upper plate (13).
10. The preparation method of the hydrophobic film based reusable double-layer digital microfluidic chip according to claim 9, wherein the preparation method comprises the following steps: and a layer of oil film is coated between the dielectric hydrophobic composite layer (6) and the electrode array layer, and the oil film material is selected from silicone oil, paraffin oil or edible oil and the like.
CN201910939704.8A 2019-09-30 2019-09-30 Reusable double-layer digital microfluidic chip based on hydrophobic film and rapid preparation method Pending CN110653011A (en)

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