WO2022134035A1 - 微流控基板、微流控装置及其驱动方法 - Google Patents

微流控基板、微流控装置及其驱动方法 Download PDF

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Publication number
WO2022134035A1
WO2022134035A1 PCT/CN2020/139526 CN2020139526W WO2022134035A1 WO 2022134035 A1 WO2022134035 A1 WO 2022134035A1 CN 2020139526 W CN2020139526 W CN 2020139526W WO 2022134035 A1 WO2022134035 A1 WO 2022134035A1
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Prior art keywords
electrode
substrate
module
layer
electrodes
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PCT/CN2020/139526
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English (en)
French (fr)
Inventor
樊博麟
高涌佳
赵莹莹
古乐
姚文亮
魏秋旭
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京东方科技集团股份有限公司
北京京东方传感技术有限公司
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Priority to PCT/CN2020/139526 priority Critical patent/WO2022134035A1/zh
Priority to EP20966600.7A priority patent/EP4151312A4/en
Priority to CN202080003636.5A priority patent/CN114981009A/zh
Priority to US17/606,716 priority patent/US20220395826A1/en
Publication of WO2022134035A1 publication Critical patent/WO2022134035A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/50273—Containers 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0424—Dielectrophoretic forces

Definitions

  • the present disclosure relates to the field of biological detection, and in particular, to a microfluidic substrate, a microfluidic device and a driving method thereof.
  • Microfluidics is a technology for precise control and manipulation of micro-scale fluids. Through this technology, basic operation units such as sample preparation, reaction, separation, and detection involved in the detection and analysis process can be integrated into a centimeter-scale chip. superior. Microfluidic technology is generally used in the analysis process of trace drugs in the fields of biology, chemistry, and medicine. Microfluidic devices have advantages such as low sample consumption, fast detection speed, easy operation, multi-functional integration, small size, and easy portability, and have great application potential in biology, chemistry, medicine and other fields.
  • a first substrate for a microfluidic device includes: a first region, the first region including at least one first module for generating droplets, the first module including a first electrode pair and a second electrode pair, wherein the first An electrode pair is arranged in a crisscross pattern with the second electrode pair, the first electrode pair includes a first electrode and a second electrode, and the second electrode pair includes a third electrode and a fourth electrode.
  • the width of the first electrode gradually decreases along the first direction, and the width of the second electrode gradually increases along the first direction.
  • the width of the third electrode gradually decreases along a second direction
  • the width of the fourth electrode gradually increases along the second direction
  • the second direction is perpendicular to the first direction
  • the outer edges of the first electrode, the second electrode, the third electrode and the fourth electrode form a quadrilateral.
  • the outer edges of the first electrode, the second electrode, the third electrode, and the fourth electrode form a square.
  • the facing outer edges of the first and second electrodes have a radius of curvature greater than one quarter of the side length of the square.
  • the first and second electrodes are semicircular in shape.
  • the facing outer edges of the first and second electrodes have a radius of curvature that is less than one quarter of the side length of the square.
  • the shapes of the first and second electrodes are isosceles triangles.
  • the pattern formed by the first electrode, the second electrode, the third electrode, and the fourth electrode is a center-symmetric pattern.
  • the shapes of the third and fourth electrodes match the shapes of the first and second electrodes.
  • the first module further includes a fifth electrode, a sixth electrode, a seventh electrode and a fifth electrode, a sixth electrode, and a seventh electrode arranged in sequence along the second direction upstream of the first electrode, the second electrode, the third electrode, and the fourth electrode.
  • an electrode, and an eighth electrode located downstream of the first electrode, the second electrode, the third electrode, and the fourth electrode, the sixth electrode includes a concave portion, and at least a portion of the seventh electrode is located at the bottom of the sixth electrode in the recess.
  • At least half of the width of the seventh electrode in the second direction is located in the recess of the sixth electrode.
  • a gap exists between each of the first to eighth electrodes, and the gap has a constant width.
  • the first area is selected from at least one of a sample and reagent area storage area and a detergent storage area.
  • the first substrate further includes a second region and a third region, the third region includes a second module, a third module and a fourth module, the second modules are connected by a first electrode path To the second zone, the third and fourth modules are connected to the second zone by a second electrode path.
  • the second zone includes a purification zone
  • the third zone includes a sample extraction zone
  • the second module includes a waste liquid module
  • the third module includes a quality control module
  • the fourth module Include product modules.
  • the first substrate includes: a first substrate; a metal wiring layer on the first substrate; an insulating layer on a side of the metal wiring layer away from the first substrate an electrode layer located on the side of the insulating layer away from the first substrate; a dielectric layer located on the side of the electrode layer away from the first substrate; and a dielectric layer located away from the first substrate Hydrophobic layer on the bottom side.
  • the first, second, third and fourth modules are located in the electrode layer, each of the first, second, third and fourth modules Each electrode is connected to the metal wiring layer through a via hole penetrating the insulating layer.
  • the electrode layer is an ITO layer.
  • a microfluidic device comprising the first substrate according to the previous aspect, a second substrate cell-celled with the first substrate, and a microfluidic device located between the first substrate and the first substrate. a slit between the second substrates, wherein the second substrate comprises: a second substrate; a conductive layer on the second substrate; and a conductive layer located away from the second substrate hydrophobic layer on one side.
  • a method for driving a microfluidic device comprising: supplying electricity to a fifth electrode, a sixth electrode, and a seventh electrode; a first electrode, a second electrode, a third electrode, and a fourth electrode.
  • the electrode is powered, and the fifth electrode, the sixth electrode, and the seventh electrode are powered off; the eighth electrode is powered; the first electrode and the second electrode are powered off, and the fifth electrode, the sixth electrode, and the seventh electrode are powered at the same time;
  • the third electrode, the fourth electrode are de-energized; and the seventh electrode is de-energized.
  • FIG. 1A schematically shows a top view of a first module according to an embodiment of the present disclosure
  • FIG. 1B schematically shows a top view of a first module according to another embodiment of the present disclosure
  • FIG. 1C schematically shows a top view of a first module according to yet another embodiment of the present disclosure
  • Figure 2A schematically shows a top view of a first module according to another embodiment of the present disclosure
  • Figure 2B schematically shows a top view of a first module according to another embodiment of the present disclosure
  • Figure 3 schematically shows a cross-sectional view of the microfluidic device taken along line A-B in Figure 2B;
  • FIG. 4 schematically shows a top view of a first substrate according to an embodiment of the present disclosure
  • FIG. 5A schematically shows a top view of a second substrate according to an embodiment of the present disclosure
  • 5B schematically shows a top view of a microfluidic device according to an embodiment of the present disclosure
  • FIG. 6 shows a process diagram of using the first module shown in FIG. 2B to generate droplets
  • Figure 7 schematically illustrates a droplet breakup neck diagram
  • FIG. 8 schematically shows a top view of a microfluidic device according to another embodiment of the present disclosure.
  • a microfluidic device that works on the principle of dielectric wetting usually includes two substrates in a cell, one of which includes an electrode layer, and the electrode layer includes a plurality of planar electrodes for driving the liquid. Multiple surfaces can be designed according to actual needs. The shape and arrangement of the electrodes allow precise manipulation of the liquid. It should be noted that the shape of the electrode mentioned in the present disclosure refers to the shape of the electrode in the plane of the electrode layer.
  • the present disclosure provides a first substrate for a microfluidic device, hereinafter referred to as the first substrate.
  • the first substrate includes a first zone including at least one first module for generating droplets.
  • FIGS. 1A , 1B and 1C schematically show top views of the first module 100 in the electrode layer of the first region of the first substrate.
  • the first module 100 includes a first electrode pair (101, 102) and a second electrode pair (103, 104), and the first electrode pair and the second electrode pair are arranged in a crisscross pattern .
  • the first electrode pair includes a first electrode 101 and a second electrode 102
  • the second electrode pair includes a third electrode 103 and a fourth electrode 104.
  • the first electrode, the second electrode, the third electrode and the fourth electrode work together to assist the droplet to form a thin neck (as shown in FIG. 7 )
  • the first electrode and the second electrode can be referred to as
  • the droplet generation auxiliary electrode, the third electrode and the fourth electrode can be called supplementary electrodes
  • determine the thinnest position of the thin neck reduce the randomness of droplet breaking, improve its breaking accuracy, and then reduce the deviation coefficient of droplet generation .
  • the width of the first electrode 101 gradually decreases along the first direction D1
  • the width of the second electrode 102 gradually increases along the first direction D1 big.
  • Such a first electrode and a second electrode can assist in determining the thinnest position of the thin neck, reduce the randomness of droplet breakage, and improve its breakage accuracy.
  • the width of the third electrode 103 gradually decreases along the second direction D2
  • the width of the fourth electrode 104 gradually increases along the second direction D2
  • the second direction D2 is perpendicular to the first direction D1.
  • the first electrode, the second electrode, the third electrode and the fourth electrode work together, so that the thinnest position of the thin neck of the droplet can be more determined, and the fracture accuracy can be further improved.
  • the "width" of the first electrode 101 refers to the size of the first electrode 101 in the second direction D2
  • the "width” of the second electrode 102 refers to the size of the second electrode 102 in the second direction D2.
  • the “width” of the three electrodes 103 refers to the size of the third electrode 103 in the first direction D1
  • the "width” of the fourth electrode 104 refers to the size of the fourth electrode 104 in the first direction D1.
  • the second direction D2 and the first direction D1 are perpendicular to each other, and the liquid driven by the microfluidic device during operation flows along the second direction D2 .
  • the outer edges of the first electrode 101 , the second electrode 102 , the third electrode 103 , and the fourth electrode 104 may form a quadrilateral, such as a square, a rectangle, a parallelogram, a trapezoid, and the like. As shown in FIG. 1A , FIG. 1B and FIG. 1C , the outer edges of the first electrode 101 , the second electrode 102 , the third electrode 103 , and the fourth electrode 104 may form a square.
  • the facing outer edges of the first electrode and the second electrode may have a radius of curvature greater than a quarter of the side length of the square, as shown in Fig.
  • the first electrode 101 and the second electrode 102 may respectively have a semicircular shape (the radius of curvature of their facing outer edges is half of the side length of a square), which is suitable for high surface Droplet generation of energetic reagents is advantageous.
  • the facing outer edges of the first electrode and the second electrode have a radius of curvature smaller than a quarter of the side length of the square.
  • the first electrode 101 and the second electrode The two electrodes 102 can respectively have the shape of an isosceles triangle (the radius of curvature of the facing outer edges is much less than a quarter of the side length of the square), which is beneficial for droplet generation of low surface energy reagents of.
  • the first electrode 101 and the second electrode 102 may have the shape of an isosceles trapezoid, respectively, and the third electrode 103 and the fourth electrode 104 may have the same shape as shown in FIG. 1C .
  • Two opposing isosceles trapezoids match the shape of an isosceles triangle.
  • the pattern formed by the first electrode 101 , the second electrode 102 , the third electrode 103 , and the fourth electrode 104 may be a center-symmetric pattern. This makes the driving electric field distribution more uniform and stable, and improves the stability of droplet generation.
  • the shapes of the third electrodes 103 and the fourth electrodes 104 match the shapes of the first electrodes 101 and the second electrodes 102 .
  • the shapes of the four electrodes are matched to each other, so that the thinnest position of the thin neck of the droplet can be more determined, and the distribution of the driving electric field is stable, which can improve the precision and stability of the droplet generation at the same time.
  • the shape of the third electrode 103 and the fourth electrode 104 "matches" the shape of the first electrode 101 and the second electrode 102 means that the first electrode pair formed by the third electrode 103 and the fourth electrode 104 is the same as the shape of the first electrode 101 and the second electrode 102
  • the second electrode pair formed by the first electrode 101 and the second electrode 102 has a substantially complementary shape.
  • the shapes of the first electrode 101 , the second electrode 102 , the third electrode 103 , and the fourth electrode 104 are matched, and each electrode has a gap of constant size therebetween.
  • the first module 100 may further include upstream electrodes of the first electrode 101 , the second electrode 102 , the third electrode 103 , and the fourth electrode 104 .
  • the fifth electrode 105, the sixth electrode 106, and the seventh electrode 107 are arranged in sequence along the second direction D2, and the first electrode 101, the second electrode 102, the third electrode 103, and the fourth electrode 104 downstream of the Eight electrodes 108 , the sixth electrode 106 includes a recess, and at least a part of the seventh electrode 107 is located in the recess of the sixth electrode 106 .
  • upstream of the electrode refers to the position where the liquid driven by the microfluidic device in operation has flowed through before flowing through the electrode
  • downstream of the electrode refers to the position where the liquid driven by the microfluidic device in operation is flowing The location that will flow through after this electrode.
  • At least half of the width of the seventh electrode 107 in the second direction D2 is located in the recess of the sixth electrode 106 .
  • the size of the fifth electrode is 1 mm ⁇ 3 mm
  • the size of the sixth electrode is 2 mm ⁇ 3 mm
  • the size of the seventh electrode and the eighth electrode is 1 mm ⁇ 1 mm
  • the size of the first electrode, the second electrode, the third electrode and the The fourth electrodes together form a 1mm ⁇ 1mm square.
  • There is a gap between each electrode which in some embodiments may have a constant width, such as 10 microns.
  • the fifth electrode 102 may include two electrodes side by side.
  • gaps between each of the first to eighth electrodes there are gaps between each of the first to eighth electrodes, and the gaps may have a constant width, eg, 10 microns.
  • each electrode mentioned in the present disclosure may include one or more electrodes.
  • Those skilled in the art can make specific designs based on actual needs and processing accuracy. This is not limited.
  • a plurality of electrodes (eg, the third electrode and the fourth electrode) mentioned in the present disclosure may also be combined to form one electrode, as long as the corresponding technical effect can be achieved.
  • the shape of the electrode is also not limited to the shape shown in the drawings of the above embodiments, and the skilled person can design other suitable shapes according to actual needs.
  • Figure 3 schematically shows a cross-sectional view of the microfluidic device taken along line A-B in Figure 2B.
  • the first substrate 10 includes: a first substrate 11 , a metal wiring layer 12 located on the first substrate 11 , and an insulating layer 13 located on the side of the metal wiring layer 12 away from the first substrate 11 .
  • the electrode layer 14 located on the side of the insulating layer 13 away from the first substrate, the dielectric layer 15 located on the side of the electrode layer 14 away from the first substrate, and the hydrophobic layer 16 located on the side of the dielectric layer 15 away from the first substrate,
  • the first to eighth electrodes are located in the electrode layer 14 , each electrode is respectively connected to the metal wiring layer 14 through a via hole 17 penetrating the insulating layer 13 , and each electrode can be individually controlled to supply electricity.
  • the first substrate 11 may be a glass substrate
  • the metal wiring layer 12 may be made of a metal with low sheet resistance such as Mo metal
  • the insulating layer 13 may be made of a material such as silicon nitride or silicon dioxide.
  • the electrode layer 14 can be made of ITO material
  • the dielectric layer 15 can be made of PI film with a dielectric constant of 3.2
  • the thickness of the hydrophobic layer can be 100 nm.
  • the microfluidic device provided by the present disclosure further includes a second substrate assembled with the first substrate, and a slit 30 between the first substrate and the second substrate.
  • the second substrate 20 includes: a second substrate 21 , a conductive layer 22 on the second substrate 21 , and a side of the conductive layer 22 away from the second substrate 21 the hydrophobic layer 23 on it.
  • the second substrate may be a glass substrate, and the conductive layer 22 may be made of ITO material.
  • the liquid moves in the slit 30 between the first substrate and the second substrate under the driving force of the electrodes.
  • FIG. 6 shows a process diagram for generating droplets using the first module shown in FIG. 2B .
  • a sinusoidal signal of 180Vrms 1KHz was used, and the electrode feeding interval was 500ms.
  • the electrode feeding interval was 500ms.
  • all electrodes are 0V.
  • the fifth electrode, the sixth electrode and the seventh electrode are powered, and the droplet is deformed accordingly, as shown in Figure 6(a).
  • the electrode and the fourth electrode are powered (that is, their voltage becomes 180Vrms), while the fifth, sixth, and seventh electrodes are de-energized (that is, the recovery voltage is 0V), and the shape of the droplet is shown in Figure 6(b), and then The eighth electrode is powered, and the shape of the droplet is shown in Fig. 6(c).
  • the first electrode and the second electrode are de-energized, and the fifth electrode, the sixth electrode, and the seventh electrode are electrified at the same time.
  • the shape of the droplet is shown in Figure 6(d), and then the third electrode and the fourth electrode are de-energized.
  • the droplet is formed as shown in Figure 6(e)
  • the seventh electrode is de-energized, and the shape of the droplet is shown in Figure 6(f), and the formation of the droplet is completed.
  • the first electrode, the second electrode, the third electrode and the fourth electrode work together to assist the droplet to form a thin neck, determine the thinnest position of the thin neck, and reduce the droplet size
  • the randomness of fracture improves its fracture accuracy, thereby reducing the deviation coefficient of droplet generation. As shown in FIG. 2A and FIG.
  • the first electrode, the second electrode, the third electrode and the fourth electrode are combined to form the droplet neck control part 109, and the first electrode and the second electrode may be called droplet generation auxiliary electrodes,
  • the third electrode and the fourth electrode may be referred to as supplementary electrodes.
  • ⁇ is the surface tension coefficient of the liquid
  • R is the radius of curvature at the thin neck, and its direction points to the center of the circle.
  • the generation accuracy can be significantly improved. Therefore, when the first module shown in Figure 2A is used, droplets are generated. The coefficient of deviation can be significantly reduced. For low surface energy reagents or reagent systems, the surface tension coefficient is small, and the generation accuracy is higher when the auxiliary electrode with a smaller radius of curvature is used, so when the first module as shown in Figure 2B is used, a lower curvature is obtained. Radius, reducing the randomness of its thin neck formation, the droplet generation deviation coefficient can be significantly reduced.
  • the first module shown in Figure 2A can effectively improve the droplet generation accuracy and stability of high surface energy reagents (such as deionized water, repair enzymes, magnetic beads, primers, etc.).
  • high surface energy reagents such as deionized water, repair enzymes, magnetic beads, primers, etc.
  • the droplet generation CV can reach within 0.5%
  • the droplet generation CV is within 0.5%- 1%
  • the first module of the present disclosure is not used, its droplet generation CV is greater than 1%.
  • Using the first module as shown in Figure 2B can effectively improve the droplet generation accuracy and stability of low surface energy reagents (such as ethanol, transposase buffer, PCR mix, etc.).
  • the first substrate may include a first region 110 , a second region 120 , a third region 130 , and a fourth region 140 .
  • the third area 130 includes a second module 131 , a third module 132 and a fourth module 133 .
  • the second module 131 is connected to the second region 120 through the first electrode path 121
  • the third module 133 and the fourth module 134 are connected to the second region 120 through the second electrode path 122 .
  • the second module, the third module and the fourth module are connected to the second region through different electrode paths, which can avoid the mutual influence of the liquids of the respective modules and improve the precision of the microfluidic device.
  • the first area can be a sample and reagent storage area or a detergent storage area.
  • the first area 110 on the left side of FIG. 4 is a sample and reagent storage area, including 12
  • a first module as shown in FIG. 2A and two first modules as shown in FIG. 2B can store 14 kinds of samples and reagents.
  • the first area 110 in the middle of FIG. 4 is a detergent storage area, including three as shown in FIG.
  • the first module shown in 2A and the first module shown in FIG. 2B can store 4 kinds of detergents.
  • the first module may be a generation module.
  • the auxiliary electrode shape of the generation module can be designed according to the properties of different reagents.
  • the second zone may be a purification zone, consisting of 5 ⁇ 5 square electrodes of 1 mm ⁇ 1 mm.
  • the third area may be a sample output area, wherein the second module may be a waste liquid module, the third module may be a quality control module, and the fourth module may be a product module.
  • the waste liquid module is connected to the purification zone through the first electrode path, and the quality control module and the product module are connected to the purification zone through the second electrode path.
  • the first electrode path and the second electrode path may be formed of square electrodes of 1 mm ⁇ 1 mm.
  • the fourth zone can be a temperature control zone, and the temperature control zone can be composed of three zones (for example, the first temperature zone 141, the second temperature zone 142 and the third temperature zone 143 shown in FIG. Each area consists of 5 ⁇ 5 square electrodes of 1 mm ⁇ 1 mm.
  • the above-mentioned areas are connected by square electrodes of 1 mm ⁇ 1 mm, and the relative position and connection method of each area
  • FIG. 5A schematically shows a top view of the second substrate of the microfluidic device
  • FIG. 5B schematically shows a top view of the microfluidic device.
  • a sample inlet hole 40 eg, a sample inlet hole with a diameter of 0.9mm
  • sampling holes such as sampling holes with a diameter of 2 mm
  • Above the third module is a third sampling hole 53 .
  • waste liquid sampling port and the quality control and product sampling ports are connected to the purification area using different paths, which can effectively avoid sample contamination, thereby improving the accuracy of the microfluidic device.
  • the first module may include a plurality of droplet neck control sections.
  • 8 schematically shows a top view of a microfluidic device according to another embodiment of the present disclosure.
  • the first module 110 on the left includes two droplet neck control parts 109 as shown in FIG. 2A
  • the first module 110 on the right includes two droplet necks as shown in FIG. 2B control unit 109 .
  • This arrangement can obtain smaller droplets on the basis of small droplets, further improving the accuracy and stability of droplet generation.
  • an interdigitated electrode arrangement may be adopted between two electrodes of the fifth electrode 105 and between the fifth electrode 105 and the sixth electrode 106 .

Abstract

本公开涉及微流控基板、微流控装置及其驱动方法。该微流控基板包括第一区，第一区包括用于生成液滴的第一模块，第一模块包括第一电极对和第二电极对，其中，第一电极对与第二电极对呈十字交叉布置，第一电极对包括第一电极和第二电极，第二电极对包括第三电极和第四电极。

Description

微流控基板、微流控装置及其驱动方法 技术领域
本公开涉及生物检测领域，具体涉及微流控基板、微流控装置及其驱动方法。
背景技术
微流控技术(Microfluidics)是一种精确控制和操控微尺度流体的技术，通过该技术，可以把检测分析过程中涉及的样品制备、反应、分离、检测等基本操作单元集成到一块厘米级芯片上。微流控技术一般应用于生物、化学、医药等领域的微量药品的分析过程。微流控装置具有诸如样品消耗少、检测速度快、操作简便、多功能集成、体积小和便于携带等优点，在生物、化学、医药等领域有着巨大的应用潜力。
公开内容
根据本公开的一方面，提供了一种用于微流控装置的第一基板。所述第一基板包括：第一区，所述第一区包括至少一个用于生成液滴的第一模块，所述第一模块包括第一电极对和第二电极对，其中，所述第一电极对与所述第二电极对呈十字交叉布置，所述第一电极对包括第一电极和第二电极，所述第二电极对包括第三电极和第四电极。
在一些实施例中，所述第一电极的宽度沿第一方向逐渐减小，所述第二电极的宽度沿第一方向逐渐增大。
在一些实施例中，所述第三电极的宽度沿第二方向逐渐减小，所述第四电极的宽度沿第二方向逐渐增大，所述第二方向与所述第一方向垂直。
在一些实施例中，所述第一电极、第二电极、第三电极、第四电极的外边缘形成四边形。
在一些实施例中，所述第一电极、第二电极、第三电极、第四电极的外边缘形成正方形。
在一些实施例中，所述第一电极和第二电极相面对的外边缘具有大于所述正方形的边长的四分之一的曲率半径。
在一些实施例中，所述第一电极和第二电极的形状是半圆形。
在一些实施例中，所述第一电极和第二电极相面对的外边缘具有小于所述正方形的边长的四分之一的曲率半径。
在一些实施例中，其中，所述第一电极和第二电极的形状是等腰三角形。
在一些实施例中，所述第一电极、第二电极、第三电极、第四电极组成的图形是中心对称图形。
在一些实施例中，所述第三电极和第四电极的形状与所述第一电极和第二电极的形状相匹配。
在一些实施例中，所述第一模块还包括位于所述第一电极、第二电极、第三电极、第四电极上游的沿第二方向依次排列的第五电极、第六电极、第七电极，以及位于所述第一电极、第二电极、第三电极、第四电极下游的第八电极，所述第六电极包括凹部，所述第七电极的至少一部分位于所述第六电极的凹部中。
在一些实施例中，所述第七电极在第二方向上的宽度的至少一半位于所述第六电极的凹部中。
在一些实施例中，所述第五电极和第六电极之间是叉指电极布置。
在一些实施例中，第一至第八电极中的各个电极之间均存在间隙，所述间隙具有恒定的宽度。
在一些实施例中，所述第一区选自样品及试剂区存储区、洗涤剂存储区中的至少一个。
在一些实施例中，所述第一基板还包括第二区和第三区，所述第三区包括第二模块、第三模块和第四模块，所述第二模块通过第一电极路径连接到所述第二区，所述第三模块和第四模块通过第二电极路径连接到所述第二区。
在一些实施例中，所述第二区包括纯化区，所述第三区包括出样区，所述第二模块包括废液模块，所述第三模块包括质控模块，所述第四模块包括产物模块。
在一些实施例中，所述第一基板包括：第一衬底；位于所述第一衬底上的金属走线层；位于所述金属走线层远离所述第一衬底一侧的绝缘层；位于所述绝缘层远离所述第一衬底一侧的电极层；位于所述电极层远离所述第一衬底一侧的介质层；以及位于所述介质层远离所 述第一衬底一侧的疏水层。
在一些实施例中，所述第一模块、第二模块、第三模块和第四模块位于所述电极层中，所述第一模块、第二模块、第三模块和第四模块中的每个电极通过贯穿所述绝缘层的过孔与所述金属走线层连接。
在一些实施例中，所述电极层是ITO层。
根据本公开的另一方面，提供了一种微流控装置，包括根据前一方面所述的第一基板、与所述第一基板对盒的第二基板，以及位于所述第一基板和所述第二基板之间的狭缝，其中，所述第二基板包括：第二衬底；位于所述第二衬底上的导电层；以及位于所述导电层远离所述第二衬底的一侧上的疏水层。
根据本公开的另一方面，提供了一种微流控装置的驱动方法，包括：第五电极、第六电极、第七电极给电；第一电极、第二电极、第三电极、第四电极给电，同时第五电极、第六电极、第七电极去电；第八电极给电；第一电极和第二电极去电，同时第五电极、第六电极、第七电极给电；第三电极、第四电极去电；以及第七电极去电。
附图说明
为了更清楚地说明本公开实施例中的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本公开的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1A示意性地示出了根据本公开一个实施例的第一模块的俯视图；
图1B示意性地示出了根据本公开另一个实施例的第一模块的俯视图；
图1C示意性地示出了根据本公开又一个实施例的第一模块的俯视图；
图2A示意性地示出了根据本公开另一个实施例的第一模块的俯视图；；
图2B示意性地示出了根据本公开另一个实施例的第一模块的俯视图；；
图3示意性地示出了沿图2B中的线A-B截取的微流控装置的截面 图；
图4示意性地示出了根据本公开一个实施例的第一基板的俯视图；
图5A示意性地示出了根据本公开一个实施例的第二基板的俯视图；
图5B示意性地示出了根据本公开一个实施例的微流控装置的俯视图；
图6示出了利用图2B所示的第一模块生成液滴的过程图；
图7示意性地示出了液滴断裂细颈图；以及
图8示意性地示出了根据本公开的另一个实施例的微流控装置的俯视图。
附图中各部分的形状和大小不反映各部分的真实比例，只是示意性地说明本公开内容。
具体实施方式
下面将结合本公开实施例中的附图，对本公开实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本公开一部分实施例，而不是全部的实施例。基于本公开中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本公开保护的范围。
发明人发现，在微流控装置中，液滴生成的精度与液体的表面能息息相关，不同表面能的试剂其生成精度不同。对于涉及多种试剂或试剂体系的应用(例如文库制备)，常规的微流控装置难以实现对所有试剂的精准操控。
利用介电润湿原理工作的微流控装置通常包括对盒的两个基板，其中一个基板包括电极层，电极层包括用于驱动液体的多个面状电极，可以根据实际需要设计多个面状电极的形状和排布，从而实现对液体的精准操控。需要说明的是，本公开所提及的电极的形状都是指电极在电极层平面中的形状。
本公开提供了一种用于微流控装置的第一基板，以下简称第一基板。第一基板包括第一区，第一区中包括至少一个用于生成液滴的第一模块。图1A、图1B和图1C示意性地示出了第一基板的第一区的电极层中的第一模块100的俯视图。如图1A、图1B和图1C所示，第一 模块100包括第一电极对(101，102)和第二电极对(103，104)，第一电极对与第二电极对呈十字交叉布置。
在一些实施例中，如图1A、图1B和图1C所示，所述第一电极对包括第一电极101和第二电极102，所述第二电极对包括第三电极103和第四电极104。
在液滴生成过程中，第一电极、第二电极、第三电极和第四电极共同起作用可辅助液滴形成细颈(如图7所示)(第一电极和第二电极可以称为液滴生成辅助电极，第三电极和第四电极可以称为补充电极)，确定细颈的最细位置，减小液滴断裂的随机性，提高其断裂精度，进而降低液滴生成的偏差系数。
在一些实施例中，如图1A、图1B和图1C所示，所述第一电极101的宽度沿第一方向D1逐渐减小，所述第二电极102的宽度沿第一方向D1逐渐增大。这样的第一电极和第二电极可以辅助确定细颈的最细位置，减小液滴断裂的随机性，提高其断裂精度。
在一些实施例中，如图1A、图1B和图1C所示，所述第三电极103的宽度沿第二方向D2逐渐减小，所述第四电极104的宽度沿第二方向D2逐渐增大，所述第二方向D2与所述第一方向D1垂直。第一电极、第二电极、第三电极和第四电极共同起作用，可以使液滴细颈的最细位置更加确定，进一步提高断裂精度。
需要理解的是，第一电极101的“宽度”是指第一电极101在第二方向D2的尺寸，第二电极102的“宽度”是指第二电极102在第二方向D2的尺寸，第三电极103的“宽度”是指第三电极103在第一方向D1的尺寸，第四电极104的“宽度”是指第四电极104在第一方向D1的尺寸。如图1A、图1B和图1C所示，第二方向D2与第一方向D1互相垂直，微流控装置在操作中所驱动的液体沿第二方向D2流动。
在一些实施例中，所述第一电极101、第二电极102、第三电极103、第四电极104的外边缘可以形成四边形，例如正方形、长方形、平行四边形、梯形等。如图1A、图1B和图1C所示，第一电极101、第二电极102、第三电极103、第四电极104的外边缘可以形成正方形。针对所驱动的液体的不同性质，在一些实施例中，所述第一电极和第二电极相面对的外边缘可以具有大于所述正方形的边长的四分之一的曲率半径，如图1A所示，第一电极101和第二电极102可以分别具有半 圆形的形状(其相面对的外边缘的曲率半径为正方形的边长的二分之一)，这种设计对于高表面能试剂的液滴生成是有利的。在一些实施例中，所述第一电极和第二电极相面对的外边缘具有小于所述正方形的边长的四分之一的曲率半径，如图1B所示，第一电极101和第二电极102可以分别具有等腰三角形的形状(其相面对的外边缘的曲率半径远远小于正方形的边长的四分之一)，这种设计对于低表面能试剂的液滴生成是有利的。
在一些实施例中，如图1C所示，第一电极101和第二电极102可以分别具有等腰梯形的形状，这时第三电极103和第四电极104可以具有如图1C所示的与两个相对的等腰梯形相匹配的等腰三角形的形状。
在一些实施例中，如图1A、图1B和图1C所示，所述第一电极101、第二电极102、第三电极103、第四电极104组成的图形可以是中心对称图形。这使得驱动电场分布更加均匀稳定，提高液滴生成的稳定性。
在一些实施例中，如图1A、图1B所示，所述第三电极103和第四电极104的形状与所述第一电极101和第二电极102的形状相匹配。四个电极的形状相互匹配可以使液滴细颈的最细位置更加确定，且驱动电场分布稳定，能够同时提高液滴生成精度和稳定性。
需要理解的是，第三电极103和第四电极104的形状与第一电极101和第二电极102的形状“相匹配”是指第三电极103和第四电极104构成的第一电极对与第一电极101和第二电极102构成的第二电极对具有大致互补的形状。在一些实施例中，如图1A、图1B所示，第一电极101、第二电极102、第三电极103和第四电极104的形状相匹配，并且各个电极之间具有恒定尺寸的间隙。
在一些实施例中，如图1A、图1B和图1C所示，所述第一模块100还可以包括位于所述第一电极101、第二电极102、第三电极103、第四电极104上游的沿第二方向D2依次排列的第五电极105、第六电极106、第七电极107，以及位于所述第一电极101、第二电极102、第三电极103、第四电极104下游的第八电极108，所述第六电极106包括凹部，所述第七电极107的至少一部分位于所述第六电极106的凹部中。
这里，电极“上游”是指微流控装置在操作中所驱动的液体在流 经该电极之前已经流经的位置，电极“下游”是指微流控装置在操作中所驱动的液体在流经该电极之后将要流经的位置。
在一些实施例中，所述第七电极107在第二方向D2上的宽度的至少一半位于所述第六电极106的凹部中。
示例性地，第五电极的尺寸为1mm×3mm，第六电极的尺寸为2mm×3mm，第七电极和第八电极的尺寸为1mm×1mm，第一电极、第二电极、第三电极和第四电极共同组成一个1mm×1mm的正方形。各个电极之间均存在间隙，在一些实施例中，所述间隙可以具有恒定的宽度，例如10微米。
在一些实施例中，第五电极和第六电极之间可以是叉指电极布置。
在一些实施例中，如图2A、图2B所示，第五电极102可以包括并排的两个电极。
第一至第八电极中的各个电极之间均存在间隙，这些间隙可以具有恒定的宽度，例如10微米。
实际上，本公开提到的每个电极都可以包括一个或多个电极，电极数量越多，对液体的操控越精细，本领域技术人员可以根据实际需求结合加工精度进行具体设计，本公开对此不作限定。同时，本公开提到的多个电极(例如第三电极和第四电极)也可以组合形成一个电极，只要能起到相应的技术效果即可。电极形状也不限于上述实施例的附图示出的形状，技术人员可以根据实际需求设计其他合适的形状。
图3示意性地示出了沿图2B中的线A-B截取的微流控装置的截面图。如图3所示，第一基板10包括：第一衬底11，位于第一衬底11上的金属走线层12，位于金属走线层12远离第一衬底11一侧的绝缘层13，位于绝缘层13远离第一衬底一侧的电极层14，位于电极层14远离第一衬底一侧的介质层15，以及位于介质层15远离第一衬底一侧的疏水层16，第一至第八电极位于电极层14中，每个电极分别通过贯穿所述绝缘层13的过孔17与所述金属走线层14连接，每个电极均可被单独控制给电。在一些实施例中，第一衬底11可以是玻璃衬底，金属走线层12可以用Mo金属等方块电阻较低的金属制备，绝缘层13可以用氮化硅、二氧化硅等材料制备，电极层14可以用ITO材料制备，介质层15可以用介电常数为3.2的PI膜制备，疏水层厚度可以为100nm。
本公开提供的微流控装置还包括与第一基板对盒的第二基板，以及第一基板和第二基板之间的狭缝30。如图3所示，第二基板20包括：第二衬底21，位于所述第二衬底21上的导电层22，以及位于所述导电层22远离所述第二衬底21的一侧上的疏水层23。第二衬底可以是玻璃衬底，导电层22可以用ITO材料制备。液体在第一基板和第二基板之间的狭缝30中在电极的驱动驱动下运动。
以图2B中所示的第一模块为例，详细描述利用本公开提供的微流控装置生成液滴的过程。图6示出了利用图2B所示的第一模块生成液滴的过程图。在液滴操控过程中，采用180Vrms 1KHz的正弦信号，电极给电间隔500ms。初始状态，所有电极均为0V，首先第五电极、第六电极和第七电极给电，液滴发生相应形变，如图6(a)所示，之后第一电极、第二电极、第三电极和第四电极给电(即其电压变为180Vrms)，同时第五电极、第六电极、第七电极去电(即恢复电压0V)，液滴形状如图6(b)所示，然后第八电极给电，液滴形状如图6(c)所示。此后第一电极和第二电极去电，同时第五电极、第六电极、第七电极给电，此时液滴形状如图6(d)所示，之后第三电极、第四电极去电，此时液滴形成如图6(e)所示，最后第七电极去电，此时液滴形状如图6(f)所示，完成液滴的生成。
在液滴生成过程中会形成一个液体的细颈(如图7所示)，之后液体在细颈处发生断裂，由于液滴断裂过程存在随机性，因此液滴每次断裂位置存在偏差，会导致生成液滴的大小存在不同，使得其偏差系数(coefficient of variation，CV)较大。当采用本公开提供的微流控装置时，第一电极、第二电极、第三电极和第四电极共同起作用可以辅助液滴形成细颈，确定细颈的最细位置，减小液滴断裂的随机性，提高其断裂精度，进而降低液滴生成的偏差系数。如图2A和图2B所示，第一电极、第二电极、第三电极和第四电极组合形成液滴细颈控制部109，第一电极和第二电极可以称为液滴生成辅助电极，第三电极和第四电极可以称为补充电极。
第一电极及第二电极的曲率半径越小，其断裂精度越高，但是由于液体的表面张力作用，液滴细颈的曲率半径无法无限的缩小，由表面张力引入的压强可通过下式描述：
p＝γ/R
其中γ为液体的表面张力系数，R为细颈处的曲率半径，其方向指向圆心处。通过第一电极、第二电极、第三电极和第四电极辅助液滴形成此细颈时是利用介电润湿效应控制液滴形状，当R减小时压强P增大，维持液滴形状所需的外力(介电润湿效应产生的力)需相应增大，但是介电润湿效应所产生的驱动力(即，能克服的压强)是一定的，因此液滴曲率半径无法无限制的减小。对于高表面能试剂或试剂体系，其表面张力系数较大，当采用较大曲率半径的辅助电极时，就能够明显提高生成精度，因此采用如图2A所示的第一模块时，液滴生成偏差系数即可明显降低。对于低表面能试剂或试剂体系，其表面张力系数较小，当采用较小曲率半径的辅助电极时其生成精度较高，因此采用如图2B所示的第一模块时，获得较低的曲率半径，降低其细颈形成的随机性，液滴生成偏差系数能够明显降低。
经测试，采用如图2A所示的第一模块，可有效提高高表面能试剂(如去离子水、修复酶、磁珠、引物等)的液滴生成精度与稳定性。以去离子水为例，使用如图2A所示的第一模块时，液滴生成CV可达0.5％以内，采用如图2B所示的第一模块时，其液滴生成CV在0.5％-1％之间，而当不使用本公开的第一模块时，其液滴生成CV大于1％。采用如图2B所示的第一模块，可有效提高低表面能试剂(如乙醇、转座酶缓冲液、PCR mix等)的液滴生成精度与稳定性。以转座酶储存缓冲液为例，采用如图2B所示的第一模块时，其液滴生成CV可达0.3％以内，而采用如图2A所示的第一模块时，其液滴生成CV在0.7％-0.9％之间，当不使用本公开的第一模块时，其液滴生成CV约为2％左右。
在一些实施例中，如图4所示，第一基板可以包括第一区110，第二区120，第三区130，第四区140。其中，第三区130包括第二模块131、第三模块132和第四模块133。第二模块131通过第一电极路径121连接到所述第二区120，所述第三模块133和第四模块134通过第二电极路径122连接到所述第二区120。第二模块与第三模块和第四模块通过不同的电极路径连接到第二区，可以避免各个模块的液体相互影响，提高微流控装置的精度。
以基于微流控的文库制备应用为例，第一区可以是样品及试剂储存区或洗涤剂储存区，示例性地，图4左侧的第一区110是样品及试剂存储区，包括12个如图2A所示的第一模块和2个如图2B所示的第 一模块，可以存储14种样品及试剂，图4中间的第一区110是洗涤剂存储区，包括3个如图2A所示的第一模块和1个如图2B所示的第一模块，可以存储4种洗涤剂。在第一区中，第一模块可以是生成模块。可以根据不同试剂的性质设计生成模块的辅助电极形状。第二区可以是纯化区，由5×5个1mm×1mm的正方形电极组成。第三区可以是出样区，其中第二模块可以是废液模块，所述第三模块可以是质控模块，所述第四模块是可以是产物模块。废液模块通过第一电极路径连接到纯化区，质控模块和产物模块通过第二电极路径连接到纯化区。第一电极路径和第二电极路径可以由1mm×1mm的正方形电极形成。第四区可以是温控区，温控区可以由三个区域(例如图4所示的第一温区141、第二温区142和第三温区143)组成，能够分别控温，每个区域由5×5个1mm×1mm的正方形电极组成。上述各个区由1mm×1mm的正方形电极连接，每个区的相对位置及连接方法见图4。
图5A示意性地示出了微流控装置的第二基板的俯视图，图5B示意性地示出了微流控装置的俯视图。如图5A和图5B所示，上述所有第一模块距第五电极一定距离(例如0.5mm)处，在第二基板上均存在一个入样孔40(例如直径为0.9mm的入样孔)。在出样区的三个模块的最后两个电极上方均存在取样孔(例如直径为2mm的取样孔)，第二模块上方为第一取样孔51，第三模块上方为第二取样孔52，第三模块上方为第三取样孔53。
废液取样口与质控及产物取样口使用不同的路径与纯化区相连接，能够有效避免样品污染，进而提供微流控装置的精度。
下面以文库制备流程为例对本公开提供的微流控装置的使用方法进行说明：
(1)将两种低表面能试剂，PCR mix和转座酶储存缓冲液置于样品及试剂储存区的如图2B所示的生成模块中，将其他约十种高表面能试剂及样品置于如图2A所示的生成模块中。将乙醇置于洗涤剂存储区的如图2B所示的生成模块中，磁珠及其他两种洗涤剂置于洗涤剂存储区的如图2A所示的生成模块中。
(2)控制生成DNA样本2微升，转座酶缓冲液、去离子水8微升，于温控区的第一个温区混合，55℃保温5min；
(3)保温结束后向上述反应体系加入1微升蛋白酶缓冲液，55℃ 保温5min，之后控制此试剂体系到第三个温区95℃保温5min；
(4)保温结束后向上述反应体系加入PCR mix 12微升、引物2微升，之后控制此试剂体系到第二温区，72℃保温5min，此后控制上述反应体系到第三温区95℃保温1min。之后控制第三温区温度为95℃，第二温区温度为65℃，第一温区为72℃。控制上述反应体系到第三温区保温30s，到第二温区保温30s，到第一温区保温2min，重复此过程15次，最后控制此反应体系到第三温区保温10min。
(5)控制温控区恢复常温，驱动上述反应体系到纯化区D，并向纯化区D加入磁珠10微升，进行纯化，废液由出样区的第一取样孔取出，之后加入乙醇20微升进行洗涤，重复乙醇洗涤4次，废液同样由第一取样孔取出。此后加入15微升去离子水进行洗涤。
(6)取上述反应体系1微升，进行质控，由第二取样口取出。
(7)控制上述产物到第一温区，加入6微升修复酶，并常温保温5min，之后升温到65℃保温5min。
(8)控制上述产物到纯化区D，按照步骤(5)进行纯化。
(9)取上述产物加入5微升接头，10微升连接酶，室温保温10min，之后按照步骤(5)使用清洗缓冲液20微升清洗4次，之后取1微升产物进行质控，最后由第三取样孔取出所有产物，完成建库。
在另一些实施例中，第一模块中可以包括包括多个液滴细颈控制部。图8示意性地示出了根据本公开的另一个实施例的微流控装置的俯视图。如图8所示，左侧的第一模块110包括两个如图2A所示的液滴细颈控制部109，右侧的第一模块110包括两个如图2B所示的液滴细颈控制部109。这种布置可以在小液滴的基础上获得更小的液滴，进一步提高液滴生成精度和稳定性。另外，第五电极105的两个电极之间，以及第五电极105和第六电极106之间可以采用叉指电极布置。
在本公开的描述中，术语“上”、“下”、“左”、“右”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本公开而不是要求本公开必须以特定的方位构造和操作，因此不能理解为对本公开的限制。
在本说明书的描述中，参考术语“一个实施例”、“另一个实施例”等的描述意指结合该实施例描述的具体特征、结构、材料或者特点包含于本公开的至少一个实施例中。在本说明书中，对上述术语的 示意性表述不必须针对的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外，在不相互矛盾的情况下，本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。另外，需要说明的是，本说明书中，术语“第一”、“第二”等仅用于描述目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。
如本领域技术人员将理解的，尽管在附图中以特定顺序描述了本公开中方法的各个步骤，但是这并非要求或者暗示必须按照该特定顺序来执行这些步骤，除非上下文另有明确说明。附加的或可替换的，可以将多个步骤合并为一个步骤执行，以及/或者将一个步骤分解为多个步骤执行。此外，在步骤之间可以插入其他方法步骤。插入的步骤可以表示诸如本文所描述的方法的改进，或者可以与该方法无关。此外，在下一步骤开始之前，给定步骤可能尚未完全完成。
以上所述，仅为本公开的具体实施方式，但本公开的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本公开揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本公开的保护范围之内。因此，本公开的保护范围应以所述权利要求的保护范围为准。通过研究附图、公开内容和所附权利要求，本领域技术人员在实践所要求保护的发明时，可以理解和达成对所公开实施例的其它变型。权利要求中，词语“包括”不排除其它元素或步骤，单数形式的“一”“一个”“该”等术语不排除复数。在互不相同的从属权利要求中列举某些措施的纯粹事实并不表示这些措施的组合不能用于获利。权利要求中的任何附图标记不应解释为限制范围。

Claims (24)

  1. 一种用于微流控装置的第一基板，包括：
    第一区，所述第一区包括至少一个用于生成液滴的第一模块，所述第一模块包括第一电极对和第二电极对，其中，所述第一电极对与所述第二电极对呈十字交叉布置。
  2. 如权利要求1所述的第一基板，其中，所述第一电极对包括第一电极和第二电极，所述第二电极对包括第三电极和第四电极。
  3. 如权利要求2所述的第一基板，其中，所述第一电极的宽度沿第一方向逐渐减小，所述第二电极的宽度沿第一方向逐渐增大。
  4. 如权利要求3所述的第一基板，其中，所述第三电极的宽度沿第二方向逐渐减小，所述第四电极的宽度沿第二方向逐渐增大，所述第二方向与所述第一方向垂直。
  5. 如权利要求2所述的第一基板，其中，所述第一电极、第二电极、第三电极、第四电极的外边缘形成四边形。
  6. 如权利要求5所述的第一基板，其中，所述第一电极、第二电极、第三电极、第四电极的外边缘形成正方形。
  7. 如权利要求6所述的第一基板，其中，所述第一电极和第二电极相面对的外边缘具有大于所述正方形的边长的四分之一的曲率半径。
  8. 如权利要求7所述的第一基板，其中，所述第一电极和第二电极的形状是半圆形。
  9. 如权利要求6所述的第一基板，其中，所述第一电极和第二电极相面对的外边缘具有小于所述正方形的边长的四分之一的曲率半径。
  10. 如权利要求9所述的第一基板，其中，所述第一电极和第二电极的形状是等腰三角形。
  11. 如权利要求2-10中的任一项所述的第一基板，其中，所述第一电极、第二电极、第三电极、第四电极组成的图形是中心对称图形。
  12. 如权利要求2-10中的任一项所述的第一基板，其中，所述第三电极和第四电极的形状与所述第一电极和第二电极的形状相匹配。
  13. 如权利要求2-12中的任一项所述的第一基板，其中，所述第一模块还包括位于所述第一电极、第二电极、第三电极、第四电极上游的沿第二方向依次排列的第五电极、第六电极、第七电极，以及位 于所述第一电极、第二电极、第三电极、第四电极下游的第八电极，所述第六电极包括凹部，所述第七电极的至少一部分位于所述第六电极的凹部中。
  14. 如权利要求13所述的第一基板，其中，所述第七电极在第二方向上的宽度的至少一半位于所述第六电极的凹部中。
  15. 如权利要求13所述的第一基板，其中，所述第五电极和第六电极之间是叉指电极布置。
  16. 如权利要求13所述的第一基板，其中，第一至第八电极中的各个电极之间均存在间隙，所述间隙具有恒定的宽度。
  17. 如权利要求1-16中的任一项所述的第一基板，其中，
    所述第一区选自样品及试剂存储区、洗涤剂存储区中的至少一个。
  18. 如权利要求1-17中的任一项所述的第一基板，其中，
    所述第一基板还包括第二区和第三区，所述第三区包括第二模块、第三模块和第四模块，所述第二模块通过第一电极路径连接到所述第二区，所述第三模块和第四模块通过第二电极路径连接到所述第二区。
  19. 如权利要求18所述的第一基板，其中，
    所述第二区包括纯化区，所述第三区包括出样区，所述第二模块包括废液模块，所述第三模块包括质控模块，所述第四模块包括产物模块。
  20. 如权利要求1-19中任一项所述的第一基板，包括：
    第一衬底；
    位于所述第一衬底上的金属走线层；
    位于所述金属走线层远离所述第一衬底一侧的绝缘层；
    位于所述绝缘层远离所述第一衬底一侧的电极层；
    位于所述电极层远离所述第一衬底一侧的介质层；以及
    位于所述介质层远离所述第一衬底一侧的疏水层。
  21. 如权利要求20所述的第一基板，其中，所述第一模块、第二模块、第三模块和第四模块位于所述电极层中，所述第一模块、第二模块、第三模块和第四模块中的每个电极通过贯穿所述绝缘层的过孔与所述金属走线层连接。
  22. 如权利要求20所述的第一基板，其中，所述电极层是ITO层。
  23. 一种微流控装置，包括根据前述权利要求中任一项所述的第一 基板、与所述第一基板对盒的第二基板，以及位于所述第一基板和所述第二基板之间的狭缝，
    其中，所述第二基板包括：
    第二衬底；
    位于所述第二衬底上的导电层；以及
    位于所述导电层远离所述第二衬底的一侧上的疏水层。
  24. 一种用于如权利要求23所述的微流控装置的驱动方法，包括：
    第五电极、第六电极、第七电极给电；
    第一电极、第二电极、第三电极、第四电极给电，同时第五电极、第六电极、第七电极去电；
    第八电极给电；
    第一电极和第二电极去电，同时第五电极、第六电极、第七电极给电；
    第三电极、第四电极去电；以及
    第七电极去电。
PCT/CN2020/139526 2020-12-25 2020-12-25 微流控基板、微流控装置及其驱动方法 WO2022134035A1 (zh)

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