WO2020020344A1 - 数字微流控芯片及数字微流控系统 - Google Patents

数字微流控芯片及数字微流控系统 Download PDF

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Publication number
WO2020020344A1
WO2020020344A1 PCT/CN2019/097899 CN2019097899W WO2020020344A1 WO 2020020344 A1 WO2020020344 A1 WO 2020020344A1 CN 2019097899 W CN2019097899 W CN 2019097899W WO 2020020344 A1 WO2020020344 A1 WO 2020020344A1
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Prior art keywords
driving
digital microfluidic
layer
droplet
microfluidic chip
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PCT/CN2019/097899
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English (en)
French (fr)
Inventor
吕明阳
李月
李彦辰
李金钰
冯大伟
赵宇
王冬
郭旺
王海龙
耿越
蔡佩芝
庞凤春
古乐
车春城
崔皓辰
赵莹莹
赵楠
肖月磊
廖辉
Original Assignee
京东方科技集团股份有限公司
北京京东方光电科技有限公司
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Priority to US16/641,126 priority Critical patent/US11691147B2/en
Publication of WO2020020344A1 publication Critical patent/WO2020020344A1/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
    • B01L3/50273—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
    • 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
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0663—Whole sensors
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • 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
    • B01L2400/0427—Electrowetting

Definitions

  • the present disclosure relates to the field of biological detection and biochip technology, and in particular, to a digital microfluidic chip and a digital microfluidic system.
  • Digital microfluidic technology can precisely control the movement of droplets, realize the fusion and separation of droplets, and complete various biochemical reactions. Compared with general microfluidic technology, digital microfluidic technology can operate liquid accurately to each droplet, complete the target reaction with less reagent volume, and control the reaction rate and reaction progress more accurately.
  • An embodiment of the present disclosure provides a digital microfluidic chip, including:
  • a first hydrophobic layer which is located on a side surface of the lower substrate facing the upper substrate;
  • a second hydrophobic layer which is located on a side surface of the upper substrate facing the lower substrate, and a space between the first hydrophobic layer and the second hydrophobic layer constitutes a droplet accommodation space;
  • One of the addressing circuits corresponds to at least one of the driving circuits.
  • the driving circuit includes a driving electrode located between the lower substrate and the first hydrophobic layer, and a driving electrode located between the upper substrate and the second hydrophobic layer. Between reference electrodes; the reference electrodes of the driving circuits are connected to each other to form an integrated structure;
  • the digital microfluidic chip further includes a first insulating layer located between the layer where the driving electrode is located and the first hydrophobic layer, and a first insulating layer located between the layer where the reference electrode is located and the second hydrophobic layer. Second insulation layer.
  • the addressing circuit includes a bottom electrode, a photoelectric conversion layer, and a top electrode that are stacked and disposed between the lower substrate and the first hydrophobic layer.
  • the bottom electrode is closer to the lower substrate than the top electrode, and the top electrode is a transparent electrode.
  • the layer where the top electrode is located and the layer where the driving electrode is located are the same film layer.
  • the top electrode and an adjacent one of the driving electrodes are connected to each other to form an integrated structure.
  • the layer where the top electrode is located is located on a side of the layer where the driving electrode is located facing the lower substrate; the orthographic projection of the top electrode on the lower substrate is determined by the The orthographic projection of the driving electrode on the lower substrate is at least partially covered.
  • the driving circuit further includes: a switching transistor between the lower substrate and a layer where the driving electrode is located, and the switching transistor includes: on the lower substrate A gate, a gate insulating layer, an active layer, and a source and a drain are stacked in this order;
  • the digital microfluidic chip further includes: a bias voltage signal line electrically connected to the bottom electrode;
  • the bottom electrode is disposed on the same layer as the source and drain, and the bias voltage signal line is disposed on the same layer as the gate.
  • an embodiment of the present disclosure further provides a digital microfluidic system, including the digital microfluidic chip and the control circuit provided by the embodiment of the present disclosure;
  • the control circuit is electrically connected to a driving circuit and an addressing circuit in the digital microfluidic chip, and the control circuit is configured to apply a driving voltage to each of the driving circuits in a driving stage to control a droplet on the
  • the droplet storage space moves according to a set path; in the detection stage, after applying a bias voltage to each of the addressing circuits, the amount of charge loss of each of the addressing circuits is detected, and the amount of charge is determined based on the amount of charge loss.
  • the position of the droplet; wherein the amount of charge loss of each of the addressing circuits is related to the intensity of the received external light.
  • control circuit is specifically configured to, in a driving stage, determine a position of the droplet, and set a position adjacent to the position of the droplet on a set moving path.
  • a driving voltage is applied next to the driving circuit, so that the droplet moves along the set path.
  • control circuit includes: a gate driving circuit and a data driving circuit;
  • the gates of each of the switching transistors in the digital microfluidic chip are electrically connected to the gate driving circuit through gate lines provided at the same layer, and the sources of the source and drain of each switching transistor are provided through the same layer.
  • a data line is electrically connected to the data driving circuit, and each of the bias voltage signal lines is electrically connected to the gate driving circuit or the data driving circuit.
  • an embodiment of the present disclosure further provides a method for driving the digital microfluidic system, including:
  • a driving voltage is applied to each of the driving circuits to control a liquid droplet to move within the liquid droplet accommodating space according to a set path;
  • the detection phase after applying a bias voltage to each of the addressing circuits, the amount of charge loss of each of the addressing circuits is detected, and the position of the droplet is determined according to the amount of charge loss;
  • the amount of charge loss of each of the addressing circuits is related to the received external light intensity.
  • the following specifically include:
  • a driving voltage is applied to the next driving circuit adjacent to the position of the liquid droplet on a set moving path according to the position of the liquid droplet being determined, so that the liquid droplet follows the setting.
  • the path moves.
  • the present disclosure also provides a digital microfluidic system, including:
  • a digital microfluidic chip comprising: an upper substrate and a lower substrate opposite to each other, a first hydrophobic layer located on a surface of the lower substrate facing a side of the upper substrate, and facing the upper substrate A second hydrophobic layer on a side surface of the lower substrate, and a plurality of driving circuits between the lower substrate and the upper substrate; wherein, between the first hydrophobic layer and the second hydrophobic layer
  • the space constitutes a droplet accommodating space; at least a part of the plurality of driving circuits is set as a monitoring site;
  • the Raman scattering detection device includes: the laser head, a receiving head, and an analysis circuit, the laser head is configured to irradiate each of the monitoring sites one by one at a preset timing, and the receiving head It is configured to receive a scattering spectrum of the monitoring site, and the analysis circuit is configured to determine whether a liquid droplet is present at the monitoring site according to the scattering spectrum fed back by the receiving head.
  • the present disclosure also provides a positioning method for a digital microfluidic system, including:
  • the laser head in the Raman scattering detection device is used to irradiate the position where the droplets are to be moved, and then the receiving head in the Raman scattering detection device is used to collect and pull Mann scattering spectrum
  • controlling the liquid droplet in the digital microfluidic chip to move on a set path specifically includes:
  • the Raman scattering spectrum determined at the crossing position and subsequent detection positions is not the same as the Raman scattering spectrum determined by the detection position before the crossing position. At the same time, it is determined that a reaction occurs at each intersection between the droplets.
  • FIG. 1 is a schematic structural diagram of a digital microfluidic system according to an embodiment of the present disclosure
  • FIG. 2 is another schematic structural diagram of a digital microfluidic system according to an embodiment of the present disclosure
  • FIG. 3 is a schematic diagram of a digital microfluidic system according to an embodiment of the present disclosure for implementing feedback control
  • FIG. 4 is a schematic structural cross-sectional view of the digital microfluidic system shown in FIG. 2 along AA ′ and BB ′;
  • FIG. 5 is a schematic cross-sectional structure diagram of a digital microfluidic system according to an embodiment of the present disclosure
  • FIG. 6 is a schematic cross-sectional structure diagram of a digital microfluidic system according to an embodiment of the present disclosure
  • FIG. 7 is another schematic structural diagram of a digital microfluidic system according to an embodiment of the present disclosure.
  • FIG. 8 is a schematic cross-sectional structure diagram of a digital microfluidic system according to an embodiment of the present disclosure
  • FIG. 9 is a schematic flowchart of a positioning method of a digital microfluidic system according to an embodiment of the present disclosure.
  • the related active matrix digital microfluidic chip usually includes a control circuit and a driving circuit arranged in a matrix.
  • the driving circuit applies a driving voltage to the driving circuit through the control circuit, so that the liquid droplets move according to a preset path.
  • the driving sequence has been determined in advance, if there is no droplet position feedback mechanism, it will affect subsequent processes.
  • the method for positioning droplets is mainly based on a feedback control system of a sensor. It is common to use a change in electrical signals to determine the position of a droplet.
  • the active matrix digital microfluidic chip is often configured to detect biochemical reactions, the electrical signal may be very weak and the change in droplet composition will cause the electrical signal to change, so the method is not accurate enough.
  • embodiments of the present disclosure provide a digital microfluidic chip and a digital microfluidic system.
  • the specific implementations of the digital microfluidic chip and the digital microfluidic system provided by the embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings. It should be noted that the embodiments described in this specification are only a part of the embodiments of the disclosure, but not all the embodiments; and in the case of no conflict, the embodiments in the disclosure and the features in the embodiments can be combined with each other; In addition, based on the embodiments in the present disclosure, all other embodiments obtained by a person of ordinary skill in the art without making creative efforts fall within the protection scope of the present disclosure.
  • a digital microfluidic chip according to an embodiment of the present disclosure, as shown in FIGS. 4 to 6, includes:
  • the first hydrophobic layer 105 is located on a surface of the lower substrate 102 facing the upper substrate 101;
  • the second hydrophobic layer 108 is located on a side surface of the upper substrate 101 facing the lower substrate 102, and a space between the first hydrophobic layer 105 and the second hydrophobic layer 108 constitutes a droplet accommodation space 109;
  • a plurality of driving circuits 001 and a plurality of addressing circuits 002 are located between the lower substrate 102 and the upper substrate 101; wherein one addressing circuit 002 corresponds to at least one driving circuit 001.
  • an embodiment of the present disclosure further provides a digital microfluidic system, as shown in FIG. 1 and FIG. 2, including the above-mentioned digital microfluidic chip 1 and control circuit 003 provided by the embodiment of the present disclosure;
  • the control circuit 003 is electrically connected to the driving circuit 001 and the addressing circuit 002 in the digital microfluidic chip 1.
  • the control circuit 003 is configured to apply a driving voltage to each of the driving circuits 001 in the driving stage to control the droplet volume in the droplet volume.
  • the setting space 109 moves according to the set path; in the detection phase, after applying a bias voltage to each addressing circuit 002, the charge loss of each addressing circuit 002 is detected, and the position of the droplet is determined according to the charge loss;
  • the amount of charge loss of the addressing circuit 002 is related to the received external light intensity.
  • the external light received by the addressing circuit 002 corresponding to the position of the liquid droplet is due to the effects of the liquid droplet on refraction, scattering, and the like.
  • the intensity is different from the intensity of external light received by other addressing circuits 002 not covered by droplets, and because the amount of charge loss of each addressing circuit 002 is related to the intensity of external light received by it, the The amount of charge loss can determine the location of the droplet.
  • the control circuit 003 can control the movement of the liquid droplets. Therefore, the above-mentioned digital microfluidic system provided by the embodiment of the present disclosure is used to realize the function of driving the liquid droplets and to accurately position the liquid droplets.
  • one addressing circuit 002 may correspond to one driving circuit 001, that is, one addressing circuit is provided around each driving circuit 001.
  • the circuit 002 monitors the presence or absence of a droplet at the position of each driving circuit 001 through the addressing circuit 002.
  • one addressing circuit 002 can correspond to multiple driving circuits 001, that is, multiple driving circuits 001 share one surrounding addressing circuit 002, and whether there is a droplet at the same time at multiple driving circuit 001 locations through one addressing circuit 002 To monitor.
  • the control circuit 003 may be specifically configured to, in the driving stage, determine the position of the droplet, and set the position adjacent to the position of the droplet on the set moving path.
  • the next driving circuit 001 applies a driving voltage to move the droplets along a set path.
  • the control circuit 003 can convert the charge change of the addressing circuit 002 corresponding to the driving circuit 001 where the droplet is located into a driving voltage, and load the driving voltage on a preset motion path adjacent to the driving circuit 001 where the droplet is located.
  • the next driving circuit 001 makes the liquid droplet move according to a preset path. In this way, feedback control is achieved, and the effect of droplet stagnation on experimental results or experimental products is avoided.
  • FIG. 3 it is a schematic diagram of the principle of implementing feedback control of the digital microfluidic system provided by the embodiment of the present disclosure.
  • the preset motion path of the droplet in FIG. 3 is from left to right, that is, the droplet gradually moves from left to right.
  • the droplet moves to the area where the third driving circuit 001 from the left is located, then the charge loss amount of the addressing circuit 002 corresponding to the third driving circuit 001 from the left is converted into the driving voltage by the control circuit 003, and
  • the driving voltage is applied to the fourth driving circuit 001 from the left, so that the droplet moves from the area where the third driving circuit 001 is located from the left to the area where the fourth driving circuit 001 is located from the left. In this way, the influence caused by the stagnation of liquid droplets is avoided.
  • FIG. 2 is a schematic cross-sectional structure view along the line AA ′ and BB ′ of the digital microfluidic chip provided in the embodiment of the present disclosure.
  • the left side of the dotted line is a schematic cross-sectional structure along AA ′
  • the right side of the dotted line is a cross-sectional structural diagram along BB ′.
  • the driving circuit 001 may specifically include a driving electrode 103 located between the lower substrate 102 and the first hydrophobic layer 105, and a driving electrode 103 located between the lower substrate 102 and the first hydrophobic layer 105.
  • the reference electrode 106 between the upper substrate 101 and the second hydrophobic layer 108; and since the reference electrode 106 is generally loaded with a fixed potential, the reference electrodes 106 of the driving circuits 001 can be connected to each other to form an integrated structure, so as to facilitate the alignment
  • the reference electrode 106 of each driving circuit 001 is loaded with a fixed potential signal, which facilitates the fabrication of the reference electrode 106.
  • the driving electrodes 103 of each driving circuit 001 are independent of each other, so that the control circuit 003 can apply the driving voltage to the driving electrode 103 one by one to realize independent control of the driving circuit 001, and then control the droplet movement.
  • the digital microfluidic chip 1 may further include a first insulating layer 104 between the layer where the driving electrode 103 is located and the first hydrophobic layer 105, and a second hydrophobic layer between the layer where the reference electrode 106 is located and the second hydrophobic layer 105.
  • the second insulating layer 107 is between the layers 108.
  • the arrangement of the first insulating layer 104 can play a role in isolating the driving electrodes 103 of each driving circuit 001 from the first hydrophobic layer 105, so that the electrical signals loaded by the driving electrodes 103 will not affect the first hydrophobic layer 105. Hydrophobic performance.
  • the first insulating layer 104 can also function as a planarization layer to ensure that the first hydrophobic layer 105 can be formed on a relatively flat surface.
  • the arrangement of the second insulating layer 107 can play a role in isolating the reference electrode 106 from the second hydrophobic layer 108 so that the electrical signal loaded by the reference electrode 106 will not affect the hydrophobic performance of the second hydrophobic layer 108.
  • the second insulating layer 107 can also function as a planarization layer, so as to ensure that the second hydrophobic layer 108 can be formed on a relatively flat plane, so that between the flat first hydrophobic layer 105 and the second hydrophobic layer 108 A droplet accommodating space 109 is formed therebetween, which facilitates droplet movement.
  • the addressing circuit 002 may include: a bottom electrode 203 disposed in a stack between the lower substrate 102 and the first hydrophobic layer 105. , The photoelectric conversion layer 202 and the top electrode 201, wherein the bottom electrode 203 is close to the lower substrate 102 relative to the top electrode 201.
  • the top electrode 201 is preferably a translucent electrode.
  • the top electrode 201 is a transparent electrode, such as indium tin oxide ( ITO) electrode.
  • the photoelectric conversion layer 202 has a structure such as a PN junction or a PIN junction, and can usually be made of p-doped and n-doped amorphous silicon.
  • the layer where the top electrode 201 is located and the layer where the drive electrode 103 is located may be the same film layer to simplify the process and reduce cost of production.
  • the top electrode 201 may be connected to an adjacent driving electrode 103 to form an integrated structure, that is, the top electrode of the address circuit 002. 201 can be reused as the driving electrode 103 of the driving circuit 001 corresponding to the addressing circuit 002, so that the addressing circuit 002 does not occupy too much space, and the driving electrode 103 distribution space in the digital microfluidic chip 1 is guaranteed.
  • the layer where the top electrode 201 is located may also be located on the side where the driving electrode 103 is located and the substrate 102 is down;
  • the orthographic projection of the top electrode 201 on the lower substrate 102 is covered by the orthographic projection of the drive electrode 103 on the lower substrate 102.
  • the driving electrode 103 may completely cover the top electrode 201 to ensure that the addressing circuit 002 does not occupy too much space, and may also partially cover the top electrode 201, which is not limited herein.
  • the driving circuit 001 may further include: the lower substrate 102 and the driving electrode 103 are located
  • the switching transistor 300 between layers, that is, the driving circuit 001 is an active driving.
  • the switching transistor 300 may include: a gate 301, a gate insulating layer 302, an active layer 303, and a source / drain 304 which are sequentially stacked on the lower substrate 102; Specifically, the positions of the gate electrode 301 and the active layer 303 may also be interchanged, which is not limited herein.
  • a third insulating layer 305 is generally provided between the switching transistor 300 and the layer where the driving electrode 103 is located.
  • the drain electrode 304 a of the source and drain electrodes 304 is connected to the driving electrode 103 through a via hole penetrating through the third insulating layer 305.
  • the digital microfluidic chip 1 may further include: Connected bias voltage signal line 033;
  • the bottom electrode 203 can be disposed on the same layer as the source and drain electrodes 304, and the bias voltage signal line 033 can be disposed on the same layer as the gate electrode 301 to save the number of film layers. Specifically, the bottom electrode 203 may be connected to the bias voltage line 033 through a via hole penetrating the gate insulating layer 302.
  • the control circuit 003 may include: a gate driving circuit 031 and a data driving circuit 032; the control circuit 003 may be integrated into the digital micro-fluidic system.
  • the inside of the flow control chip 1 may also be set separately, which is not limited herein.
  • the gate 301 of each switching transistor 300 is electrically connected to the gate driving circuit 031 through a gate line 301 ′ provided on the same layer, and the source 304b of the source and drain 304 of each switching transistor 300 is connected to the data line 304 ′ provided on the same layer.
  • the data driving circuit 032 is electrically connected, and each of the bias voltage signal lines 033 is electrically connected to the gate driving circuit 031 or the data driving circuit 032.
  • FIG. 1 illustrates a situation where the bias voltage signal line 033 is electrically connected to the data driving circuit 032.
  • a bias voltage can be applied to the bottom electrode 203 of each addressing circuit 002 through the data driving circuit 032 or the gate driving circuit 031 via the bias voltage line 033 at the same time.
  • the bias voltage lines 033 connected to the bottom electrode 203 of each addressing circuit 002 can be connected together.
  • the common electrode line can be reused as the bias voltage line 033.
  • the top electrode 201 may be electrically connected to the data driving circuit 032 through a read line 034, and when the top electrode 201 and the driving electrode 103 are multiplexed into the same electrode, the data line 304 'Mux is used as the read line 034, so that the amount of charge loss of each addressing circuit 002 transmitted via the read line 034 can be read out by the data driving circuit 032.
  • the main features of the above-mentioned digital microfluidic chip and system provided by the embodiments of the present disclosure are: the function of driving the movement of the droplet and the function of positioning the droplet (ie, the addressing function) during the manufacturing process of the array substrate integrated.
  • a transparent conductive material such as ITO is used as the top electrode 201 of the addressing circuit 002 and at the same time as the driving electrode 103 of the driving circuit 001, and finally a cell array having both droplet driving and positioning is formed.
  • the timing of the digital microfluidic system is divided into a droplet driving period and a droplet detection period: during the droplet driving period, the driving electrode 103 is controlled by the switching transistor 300 to charge and discharge in a certain order to cause the droplet to move; during the droplet detection period Add the same bias voltage to the bottom electrode 203 of the addressing circuit 002.
  • the droplet moves over some of the addressing circuit 002, compared with the addressing circuit 002 not covered by the droplet, the external light passes through the droplet. The effect of refraction, scattering, etc., causes the light intensity received by the photoelectric conversion layer 202 in the addressing circuit 002 to change.
  • the data driving circuit reads the amount of charge loss of each addressing circuit 002 to obtain the real-time position of the droplet. And movement track. Further, the obtained charge loss amount signal is converted into a control signal of the next driving circuit 001 through calculation and processing of the data driving circuit, and the droplet movement is continuously driven, thereby implementing feedback control. Therefore, the above-mentioned active matrix digital microfluidic chip provided by the embodiments of the present disclosure can realize a more accurate liquid droplet operation on the one hand, and is conducive to the precise manipulation of the biological detection reaction; on the other hand, whether in the overall structure or the The manufacturing process of the addressing circuit 002 is easy to implement and the cost is low.
  • the present disclosure also provides a driving method for the above-mentioned digital microfluidic system, including:
  • a driving voltage is applied to each driving circuit to control the liquid droplet to move within the liquid droplet accommodating space according to a set path;
  • the detection phase after applying a bias voltage to each addressing circuit, the amount of charge loss of each addressing circuit is detected, and the position of the droplet is determined according to the amount of charge loss;
  • the amount of charge loss of each addressing circuit is related to the received external light intensity.
  • the foregoing driving method provided in the embodiment of the present disclosure specifically includes:
  • a driving voltage is applied to the next driving circuit adjacent to the position of the liquid droplet on the set moving path according to the position of the liquid droplet, so that the liquid droplet moves along the set path.
  • an embodiment of the present disclosure provides another digital microfluidic system, as shown in FIG. 7, including:
  • the digital microfluidic chip 1 includes an upper substrate 101 and a lower substrate 102 opposite to each other, and a first hydrophobic layer 105 located on a surface of the lower substrate 102 facing the upper substrate 101.
  • the Raman scattering detection device 2 includes a laser head 004, a receiving head 005, and an analysis circuit 006.
  • the laser head 004 is configured to illuminate each monitoring site one by one at a preset timing
  • the receiving head 005 is configured as Receiving the scattering spectrum of the monitoring site
  • the analysis circuit 006 is configured to determine whether a liquid droplet is present at the monitoring site according to the scattering spectrum fed back by the receiving head 005.
  • the Raman scattering detection device 2 can complete the function of moving between monitoring sites with the assistance of a fixed-point mobile device such as a robotic arm.
  • a fixed-point mobile device such as a robotic arm.
  • one Raman scattering detection device 2 or multiple Raman scattering detection devices 2 may be provided, which is not limited herein.
  • the driving circuit 001 may specifically include: a driving electrode 103 located between the lower substrate 102 and the first hydrophobic layer 105, and a reference electrode located between the upper substrate 101 and the second hydrophobic layer 108. 106, and a switching transistor between the lower substrate 102 and the layer where the driving electrode 103 is located, that is, the driving circuit 001 is active driving.
  • the switching transistor may include: a gate 301 and a gate insulating layer 302 which are sequentially stacked on the lower substrate 102.
  • the active layer 303 and the source / drain 304; specifically, the positions of the gate electrode 301 and the active layer 303 can also be interchanged, which is not limited herein.
  • a third insulating layer 305 is generally provided between the switching transistor 300 and the layer where the driving electrode 103 is located.
  • the drain of the source and drain electrodes 304 is connected to the driving electrode 103 through a through hole penetrating through the third insulating layer 305.
  • the digital microfluidic chip 1 may further include a first insulation layer 104 located between the layer where the driving electrode 103 is located and the first hydrophobic layer 105, and a second insulation layer located between the layer where the reference electrode 106 is located and the second hydrophobic layer 108. Layer 107.
  • Raman scattering is a fast, non-destructive, and highly specific detection method.
  • the detection time can be as short as 1 second.
  • the Raman spectra of different substances are different, which is the "fingerprint spectrum" of molecules. Therefore, the Raman spectrum of the driving circuit 001 covered with droplets must be different from the Raman spectrum of the driving circuit 001 not covered with droplets. Therefore, the laser circuit 004 is used to irradiate the driving circuit 001, and the scattering spectrum obtained from the receiving head 005 is then passed.
  • the analysis circuit can analyze the scattering spectrum to realize the positioning of the droplet position.
  • the Raman spectrum of the driving circuit 001 in which a single droplet stays must be different from the Raman spectrum of the driving circuit 001 in which two droplets stay,
  • scattering spectrum detection it can be known whether a reaction has occurred, that is, the reaction product is detected.
  • the digital microfluidic system shown in FIG. 7 can not only control the movement of the droplets, realize the positioning of the droplets, but also detect the reaction products, and the cost is low, the calculation amount is small, and the efficiency is fast.
  • an embodiment of the present disclosure provides a positioning method for the above-mentioned digital microfluidic system. As shown in FIG. 9, the method includes the following steps:
  • the laser head in the Raman scattering detection device is used to irradiate the position to which the droplet is to be moved, and then the receiving head in the Raman scattering detection device is used Collect Raman scattering spectrum;
  • Raman scattering is a fast, non-destructive, and highly specific detection method.
  • the detection time can be as short as 1 second.
  • the Raman spectra of different substances are different, which is the "fingerprint spectrum" of molecules. Therefore, the Raman spectrum of the driving circuit covered with droplets must be different from the Raman spectrum of the driving circuit not covered with droplets. Therefore, the laser circuit is used to irradiate the driving circuit, and the scattering spectrum obtained from the receiving head is used to analyze the scattering through the analysis circuit.
  • Spectrum analysis that is, monitoring the Raman scattering spectrum of the detection site, can detect the movement position of the droplet, and realize the positioning of the droplet position.
  • the above-mentioned digital microfluidic system can not only control the movement of a droplet and position the droplet, but also Realize detection of reaction products.
  • the above step S901 controls the liquid droplet in the digital microfluidic chip to move on a set path, which specifically includes: controlling the digital Different droplets in the microfluidic chip move on at least two set paths crossing;
  • the Raman scattering spectrum determined at the crossing position and subsequent detection positions is not the same as the Raman scattering spectrum determined by the detection position before the crossing position. At the same time, it was determined that the droplets reacted at the intersections.
  • the digital microfluidic system shown in FIG. 7 is used to detect the reaction of two droplets as an example. It can be seen that in FIG. 7, by applying a driving voltage to each of the driving circuits 001 on the first preset motion path and each of the driving circuits 001 on the second preset motion path, the two droplets are respectively removed from a And port b enter the drive circuit 001 where the intersection point d of the first preset motion path and the second preset movement path is located, and the two droplets fuse on the drive circuit 001 where the intersection point d is located and stay for a preset time. Move to port c; in this process, the laser head 004 irradiates each drive circuit 001 according to a preset timing.
  • Raman scattering is a fast, non-destructive, and highly specific detection method.
  • the detection time can be as short as 1 second.
  • the Raman spectra of different substances are different, which is the "fingerprint spectrum" of molecules. Therefore, if two droplets react and a new substance is generated, the Raman spectrum of the driving circuit 001 with a single droplet staying is necessarily different from the Raman spectrum of the driving circuit 001 with two droplets staying.
  • the digital microfluidic system shown in Figure 7 can not only control the movement of the droplets, realize the positioning of the droplets, but also detect the reaction products, and the cost is low, the amount of calculation is small, and the efficiency is fast.

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Abstract

一种数字微流控芯片及数字微流控系统，包括：数字微流控芯片，数字微流控芯片包括：相对而置的上基板（101）和下基板（102），位于下基板（102）和上基板（101）之间的多个驱动电路（001）和多个寻址电路（002）；控制电路（003）与驱动电路（001）和寻址电路（002）电连接，控制电路（003）被配置为在驱动阶段，对各驱动电路（001）施加驱动电压，以控制液滴在液滴容置空间（109）内按照设定路径移动；在检测阶段，对各寻址电路（002）施加偏置电压后，检测各寻址电路（002）的电荷损失量，根据电荷损失量确定液滴的位置；其中，各寻址电路（002）的电荷损失量与接收到的外界光线强度相关。

Description

数字微流控芯片及数字微流控系统
相关申请的交叉引用
本公开要求在2018年07月27日提交中国专利局、申请号为201810842202.9、申请名称为“一种有源矩阵数字微流控芯片”的中国专利申请的优先权，其全部内容通过引用结合在本公开中。
技术领域
本公开涉及生物检测及生物芯片技术领域，尤其涉及数字微流控芯片及数字微流控系统。
背景技术
数字微流控技术能够精确操控液滴移动，实现液滴的融合、分离等操作，完成各种生物化学反应。同一般微流控技术相比，数字微流控技术对液体的操作能够精确到每个液滴，以更少的试剂量完成目标反应，对反应速率和反应进度的控制更为精确。
发明内容
本公开实施例提供了一种数字微流控芯片，包括：
相对而置的上基板和下基板；
第一疏水层，位于所述下基板面向所述上基板一侧表面；
第二疏水层，位于所述上基板面向所述下基板一侧表面，所述第一疏水层与所述第二疏水层之间的空间构成液滴容置空间；以及，
多个驱动电路和多个寻址电路，位于所述下基板和所述上基板之间；
其中，一个所述寻址电路对应至少一个所述驱动电路。
可选地，在本公开提供的实施例中，所述驱动电路包括位于所述下基板与所述第一疏水层之间的驱动电极，以及位于所述上基板与所述第二疏水层 之间的参比电极；各所述驱动电路的参比电极相互连接构成一体结构；
所述数字微流控芯片还包括：位于所述驱动电极所在层与所述第一疏水层之间的第一绝缘层，位于所述参比电极所在层与所述第二疏水层之间的第二绝缘层。
可选地，在本公开提供的实施例中，所述寻址电路包括：位于所述下基板与所述第一疏水层之间层叠设置的底电极、光电转换层和顶电极，其中，所述底电极相对于所述顶电极靠近所述下基板，所述顶电极为透明电极。
可选地，在本公开提供的实施例中，所述顶电极所在层与所述驱动电极所在层为同一膜层。
可选地，在本公开提供的实施例中，所述顶电极与相邻的一个所述驱动电极相互连接构成一体结构。
可选地，在本公开提供的实施例中，所述顶电极所在层位于所述驱动电极所在层面向所述下基板的一侧；所述顶电极在所述下基板的正投影被所述驱动电极在所述下基板的正投影至少部分覆盖。
可选地，在本公开提供的实施例中，所述驱动电路还包括：位于所述下基板与所述驱动电极所在层之间的开关晶体管，所述开关晶体管包括：在所述下基板上依次层叠设置的栅极，栅绝缘层，有源层，源漏极；
所述开关晶体管和所述驱动电极所在层之间具有第三绝缘层，所述源漏极中的漏极通过贯穿所述第三绝缘层的过孔与所述驱动电极连接。
可选地，在本公开提供的实施例中，所述数字微流控芯片还包括：与所述底电极电连接的偏置电压信号线；
所述底电极与所述源漏极同层设置，所述偏置电压信号线与所述栅极同层设置。
相应地，本公开实施例还提供了一种数字微流控系统，包括：本公开实施例提供的上述数字微流控芯片，以及控制电路；
所述控制电路与所述数字微流控芯片中的驱动电路和寻址电路电连接，所述控制电路被配置为在驱动阶段，对各所述驱动电路施加驱动电压，以控 制液滴在所述液滴容置空间内按照设定路径移动；在检测阶段，对各所述寻址电路施加偏置电压后，检测各所述寻址电路的电荷损失量，根据所述电荷损失量确定所述液滴的位置；其中，各所述寻址电路的电荷损失量与接收到的外界光线强度相关。
可选地，在本公开提供的实施例中，所述控制电路具体被配置为在驱动阶段，根据确定出所述液滴的位置，对设定移动路径上与所述液滴的位置相邻的下一个所述驱动电路施加驱动电压，使所述液滴按照所述设定路径移动。
可选地，在本公开提供的实施例中，所述控制电路包括：栅极驱动电路和数据驱动电路；
所述数字微流控芯片中的各所述开关晶体管的栅极通过同层设置的栅线与所述栅极驱动电路电连接，各开关晶体管的源漏极中的源极通过同层设置的数据线与所述数据驱动电路电连接，各所述偏置电压信号线与所述栅极驱动电路或所述数据驱动电路电连接。
相应地，在本公开实施例还提供了一种上述数字微流控系统的驱动方法，包括：
在驱动阶段，对各所述驱动电路施加驱动电压，以控制液滴在所述液滴容置空间内按照设定路径移动；
在检测阶段，对各所述寻址电路施加偏置电压后，检测各所述寻址电路的电荷损失量，根据所述电荷损失量确定所述液滴的位置；
其中，各所述寻址电路的电荷损失量与接收到的外界光线强度相关。
可选地，在本公开提供的实施例中，具体包括：
在驱动阶段，根据确定出所述液滴的位置，对设定移动路径上与所述液滴的位置相邻的下一个所述驱动电路施加驱动电压，使所述液滴按照所述设定路径移动。
相应地，本公开还提供了一种数字微流控系统，包括：
数字微流控芯片，所述数字微流控芯片包括：相对而置的上基板和下基板，位于所述下基板面向所述上基板一侧表面的第一疏水层，位于所述上基 板面向所述下基板一侧表面的第二疏水层，以及位于所述下基板和所述上基板之间的多个驱动电路；其中，所述第一疏水层与所述第二疏水层之间的空间构成液滴容置空间；多个所述驱动电路中的至少部分驱动电路被设置为监测位点；
拉曼散射检测装置，所述拉曼散射检测装置包括：所述激光头、接收头和分析电路，所述激光头被配置为按预设时序逐个照射各所述监测位点，所述接收头被配置为接收所述监测位点散射光谱，所述分析电路被配置为根据所述接收头反馈的散射光谱确定监测位点是否存在液滴。
相应地，本公开还提供了一种数字微流控系统的定位方法，包括：
控制数字微流控芯片中的液滴在设定路径上移动；
在控制数字微流控芯片中的液滴移动到检测位点之前，采用拉曼散射检测装置中的激光头照射液滴将要移动到的位置后，采用拉曼散射检测装置中的接收头采集拉曼散射光谱；
在控制数字微流控芯片中的液滴移动到检测位点之后，确定所述接收头采集到的拉曼散射光谱发生变化，则确定液滴移动到检测位点。
可选地，在本公开提供的实施例中，所述控制数字微流控芯片中的液滴在设定路径上移动，具体包括：
控制所述数字微流控芯片中的不同液滴在交叉的至少两条设定路径上移动；
在确定各液滴移动到交叉位置的检测位点并停留预设时间后，在交叉位置及以后的检测位点确定的拉曼散射光谱与交叉位置之前的检测位点确定的拉曼散射光谱不同时，确定各所述液滴之间在交叉位置发生反应。
附图说明
图1为本公开实施例提供的数字微流控系统的一种结构示意图；
图2为本公开实施例提供的数字微流控系统的另一种结构示意图；
图3为本公开实施例提供的数字微流控系统实现反馈控制的原理示意图；
图4为图2所示的数字微流控系统沿AA’与BB’的剖面结构示意图；
图5为本公开实施例提供的数字微流控系统的另一种剖面结构示意图；
图6为本公开实施例提供的数字微流控系统的另一种剖面结构示意图；
图7为本公开实施例提供的数字微流控系统的另一种结构示意图；
图8为本公开实施例提供的数字微流控系统的另一种剖面结构示意图；
图9为本公开实施例提供的数字微流控系统的定位方法的流程示意图。
具体实施方式
相关有源矩阵数字微流控芯片通常包括控制电路和呈矩阵排列的驱动电路，其通过控制电路向驱动电路加载驱动电压，使得液滴按照预设路径进行运动。然而，在原材、工艺或环境问题导致驱动电路表面不平整或有杂质时，则会影响液滴运动状态。由于驱动时序已事先确定，如无液滴位置反馈机制，将影响后续进程。目前被配置为液滴定位的方法主要是基于传感器的反馈控制系统，常见的有利用电信号变化来确定液滴位置。但由于有源矩阵数字微流控芯片常被配置为检测生物化学反应，电信号可能十分微弱且液滴成分的变化会导致电信号的变化，故该方法精度不足。
针对目前液滴定位不准确的问题，本公开实施例提供了一种数字微流控芯片及数字微流控系统。下面结合附图，对本公开实施例提供的数字微流控芯片及数字微流控系统的具体实施方式进行详细的说明。需要说明的是本说明书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；并且在不冲突的情况下，本公开中的实施例及实施例中的特征可以相互组合；此外，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它实施例，都属于本公开保护的范围。
本公开实施例提供的一种数字微流控芯片，如图4至图6所示，包括：
相对而置的上基板101和下基板102；
第一疏水层105，位于下基板102面向上基板101一侧表面；
第二疏水层108，位于上基板101面向下基板102一侧表面，第一疏水层 105与第二疏水层108之间的空间构成液滴容置空间109；
多个驱动电路001和多个寻址电路002，位于下基板102和上基板101之间；其中，一个寻址电路002对应至少一个驱动电路001。
基于同一发明构思，本公开实施例还提供了一种数字微流控系统，如图1和图2所示，包括本公开实施例提供的上述数字微流控芯片1和控制电路003；
控制电路003与数字微流控芯片1中的驱动电路001和寻址电路002电连接，控制电路003被配置为在驱动阶段，对各驱动电路001施加驱动电压，以控制液滴在液滴容置空间109内按照设定路径移动；在检测阶段，对各寻址电路002施加偏置电压后，检测各寻址电路002的电荷损失量，根据电荷损失量确定液滴的位置；其中，各寻址电路002的电荷损失量与接收到的外界光线强度相关。
具体地，在本公开实施例提供的上述数字微流控芯片和系统中，由于液滴会对外界光线产生折射、散射等作用，使得液滴所在位置对应的寻址电路002接收到的外界光线强度与未被液滴覆盖的其他寻址电路002接收到的外界光线强度不同，且因各寻址电路002的电荷损失量与其接收到的外界光线强度相关，故通过检测各寻址电路002的电荷损失量即可以判断出液滴所在位置。由控制电路003可以控制液滴移动，因此采用本公开实施例提供的上述数字微流控系统实现驱动液滴移动功能的同时，实现了对液滴位置的准确定位。
具体地，在本公开实施例提供的上述数字微流控芯片和系统中，例如图1所示，一个寻址电路002可以对应一个驱动电路001，即每一个驱动电路001周围均设置一个寻址电路002，通过寻址电路002对每一个驱动电路001位置处是否存在液滴进行监控。或者，也可以一个寻址电路002对应多个驱动电路001，即多个驱动电路001共用周围的一个寻址电路002，通过一个寻址电路002对多个驱动电路001位置处是否存在液滴同时进行监控。
进一步地，对于一些移动路径较复杂的反应，一旦出现液滴停滞等现象必然会影响最终实验产物或实验结果。故在本公开实施例提供的上述数字微 流控系统中，控制电路003具体可以被配置为在驱动阶段，根据确定出液滴的位置，对设定移动路径上与液滴的位置相邻的下一个驱动电路001施加驱动电压，使液滴按照设定路径移动。具体地，控制电路003可以将液滴所在驱动电路001对应的寻址电路002的电荷变化量转换成驱动电压，并将驱动电压加载至预设运动路径上与液滴所在驱动电路001相邻的下一驱动电路001，使得液滴按照预设路径运动。如此，则实现了反馈控制，避免了液滴停滞对实验结果或实验产物的影响。
如图3所示，为本公开实施例提供的上述数字微流控系统实现反馈控制的原理示意图。可以看出，在图3中液滴的预设运动路径为自左而右，即液滴自左向右逐渐移动。某一时刻液滴运动到左起第三个驱动电路001所在区域，则将与左起第三个驱动电路001对应的寻址电路002的电荷损失量经由控制电路003转换为驱动电压，并将该驱动电压加载至左起第四个驱动电路001上，从而使得液滴由左起第三个驱动电路001所在区域，运动至左起第四个驱动电路001所在区域，由此通过反馈控制的方式，避免了液滴发生停滞造成的影响。
为更好地理解本公开的技术方案，下面对本公开实施例提供的上述数字微流控芯片和系统的一种可能的具体结构进行详细说明。需要说明的是，该具体实施例仅是为了说明本公开的技术方案，并不限制本公开。
如图4所示，为本公开实施例提供的上述数字微流控芯片的图2沿AA’与BB’的剖面结构示意图。具体地，在图4中，虚线左侧为沿AA’的剖面结构示意图，虚线右侧为沿BB’的剖面结构示意图。
可选地，在本公开实施例提供的上述数字微流控芯片中，如图4所示，驱动电路001可以具体包括位于下基板102与第一疏水层105之间的驱动电极103，以及位于上基板101与第二疏水层108之间的参比电极106；并且，由于参比电极106一般加载固定电位，因此，各驱动电路001的参比电极106可以相互连接构成一体结构，以便于对各驱动电路001的参比电极106加载固定电位信号，以及利于参比电极106的制作。而各驱动电路001的驱动电 极103均相互独立，使得控制电路003可以通过逐次对驱动电极103施加驱动电压，实现对驱动电路001的独立控制，进而可控制液滴移动。
并且，如图4所示，数字微流控芯片1还可以包括：位于驱动电极103所在层与第一疏水层105之间的第一绝缘层104，位于参比电极106所在层与第二疏水层108之间的第二绝缘层107。具体地，第一绝缘层104的设置可以起到将各驱动电路001的驱动电极103与第一疏水层105隔离的作用，以便各驱动电极103加载的电信号不会影响第一疏水层105的疏水性能，另一方面，第一绝缘层104也可以起到平坦化层的作用，以保证第一疏水层105可以在较为平坦的平面上形成。同理，第二绝缘层107的设置可以起到将参比电极106与第二疏水层108隔离的作用，以便参比电极106加载的电信号不会影响第二疏水层108的疏水性能，另一方面，第二绝缘层107也可以起到平坦化层的作用，以保证第二疏水层108可以在较为平坦的平面上形成，使得在平坦的第一疏水层105和第二疏水层108之间形成有利于液滴移动的液滴容置空间109。
可选地，在本公开实施例提供的上述数字微流控芯片中，如图4所示，寻址电路002可以包括：位于下基板102与第一疏水层105之间层叠设置的底电极203、光电转换层202和顶电极201，其中，底电极203相对于顶电极201靠近下基板102。具体地，为了保证光电转换层202能够接收外界光线顶电极201宜为半透明电极，进一步地，为了保证光电转换层202能够充分感受光强变化，顶电极201为透明电极，例如氧化铟锡(ITO)电极。在实际应用过程中，光电转换层202为PN结或PIN结等结构，通常可由p掺杂和n掺杂无定形硅制成。
可选地，在本公开实施例提供的上述数字微流控芯片中，如图4和图5所示，顶电极201所在层与驱动电极103所在层可以为同一膜层，以简化工艺，降低制作成本。
进一步地，在本公开实施例提供的上述数字微流控芯片中，如图4所示，顶电极201可以与相邻的一个驱动电极103相互连接构成一体结构，即寻址 电路002的顶电极201可以复用为与该寻址电路002对应的驱动电路001的驱动电极103，这样可以使寻址电路002不会过多占用空间，保证数字微流控芯片1中的驱动电极103分布空间。
或者，可选地，在本公开实施例提供的上述数字微流控芯片中，如图6所示，顶电极201所在层也可以位于驱动电极103所在层面向下基板102的一侧；并且，顶电极201在下基板102的正投影被驱动电极103在下基板102的正投影覆盖。具体地，驱动电极103可以完全覆盖顶电极201，保证寻址电路002不会过多占用空间，也可以部分覆盖顶电极201，在此不做限定。
可选地，在本公开实施例提供的上述数字微流控芯片中，如图1、图2、图4至图6所示，驱动电路001还可以包括：位于下基板102与驱动电极103所在层之间的开关晶体管300，即驱动电路001为有源驱动，开关晶体管300可以包括：在下基板102上依次层叠设置的栅极301，栅绝缘层302，有源层303，源漏极304；具体地，栅极301和有源层303的位置也可以互换，在此不做限定。开关晶体管300和驱动电极103所在层之间一般具有第三绝缘层305，源漏极304中的漏极304a通过贯穿第三绝缘层305的过孔与驱动电极103连接。
可选地，在本公开实施例提供的上述数字微流控芯片中，如图1、图2、如图4至图6所示，数字微流控芯片1还可以包括：与底电极203电连接的偏置电压信号线033；
底电极203可以与源漏极304同层设置，偏置电压信号线033可以与栅极301同层设置，以节省膜层数量。具体地，底电极203可以通过贯穿栅绝缘层302的过孔与偏置电压线033连接。
可选地，在本公开实施例提供的上述数字微流控系统中，如图1所示，控制电路003可以包括：栅极驱动电路031和数据驱动电路032；控制电路003可以集成于数字微流控芯片1的内部，也可以单独设置，在此不做限定。各开关晶体管300的栅极301通过同层设置的栅线301'与栅极驱动电路031电连接，各开关晶体管300的源漏极304中的源极304b通过同层设置的数据 线304'与数据驱动电路032电连接，各偏置电压信号线033与栅极驱动电路031或数据驱动电路032电连接，图1中示出了偏置电压信号线033与数据驱动电路032电连接的情况。在实际应用过程中，可通过数据驱动电路032或栅极驱动电路031经偏置电压线033向各寻址电路002的底电极203同时施加偏置电压。且为了便于数据驱动电路或栅极驱动电路向底电极203同时施加偏置电压，可与各寻址电路002的底电极203分别相连的各偏置电压线033连接到一起。此外，为简化工艺，降低制作成本，公共电极线可以复用为偏置电压线033。
具体地，在顶电极201与驱动电极103相互独立时，顶电极201可以通过读取线034与数据驱动电路032电连接，在顶电极201与驱动电极103复用为同一电极时，数据线304'复用作为读取线034，使得可通过数据驱动电路032读出经读取线034传输的每个寻址电路002的电荷损失量。
由上述描述可知，本公开实施例提供的上述数字微流控芯片和系统主要特点为：将驱动液滴移动的功能和实现液滴定位的功能(即寻址功能)在阵列基板的制作过程中集成。具体地，使用ITO等透明导电材料作为寻址电路002的顶电极201，同时作为驱动电路001的驱动电极103，最终形成液滴驱动及定位兼备的单元阵列。该数字微流控系统的时序分为液滴驱动时段和液滴检测时段：在液滴驱动时段，通过开关晶体管300控制驱动电极103按一定顺序充放电，使液滴移动；在液滴检测时段，给寻址电路002的底电极203加相同的偏置电压，当液滴移动到一些寻址电路002上方时，与未被液滴覆盖的寻址电路002相比，由于外界光线经过液滴的折射、散射等作用，使得寻址电路002中的光电转换层202接收的光强度发生变化，通过数据驱动电路读取每个寻址电路002的电荷损失量，即可得到液滴的实时位置及运动轨迹。进一步地，将得到的电荷损失量信号通过数据驱动电路的运算和处理，转化为下一驱动电路001的控制信号，继续驱动液滴移动，从而实现反馈控制。因此，本公开实施例提供的上述有源矩阵数字微流控芯片一方面，能够实现准确程度更高的液滴操作，有利于生物检测反应的精确操控；另一方面， 无论是在整体结构还是寻址电路002的制作工艺上均容易实现，且成本低。
基于同一发明构思，本公开还提供了一种上述数字微流控系统的驱动方法，包括：
在驱动阶段，对各驱动电路施加驱动电压，以控制液滴在液滴容置空间内按照设定路径移动；
在检测阶段，对各寻址电路施加偏置电压后，检测各寻址电路的电荷损失量，根据电荷损失量确定所述液滴的位置；
其中，各寻址电路的电荷损失量与接收到的外界光线强度相关。
可选地，在本公开实施例提供的上述驱动方法中，具体包括：
在驱动阶段，根据确定出液滴的位置，对设定移动路径上与液滴的位置相邻的下一个驱动电路施加驱动电压，使液滴按照设定路径移动。
基于同一发明构思，本公开实施例提供了另一种数字微流控系统，如图7所示，包括：
数字微流控芯片1，如图8所示，数字微流控芯片1包括：相对而置的上基板101和下基板102，位于下基板102面向上基板101一侧表面的第一疏水层105，位于上基板101面向下基板102一侧表面的第二疏水层108，以及位于下基板102和上基板101之间的多个驱动电路001；其中，第一疏水层105与第二疏水层108之间的空间构成液滴容置空间109；多个驱动电路001中的至少部分驱动电路001被设置为监测位点，具体可以将全部驱动电路001均设置为监测位点，可以选择部分作为监测位点，在此不做限定；
拉曼散射检测装置2，拉曼散射检测装置2包括：激光头004、接收头005和分析电路006，激光头004被配置为按预设时序逐个照射各监测位点，接收头005被配置为接收监测位点散射光谱，分析电路006被配置为根据接收头005反馈的散射光谱确定监测位点是否存在液滴。
具体地，拉曼散射检测装置2可以在机械臂等定点移动设备的协助下完成在各监测位点之间移动的功能。在数字微流控系统中，可以设置一个拉曼散射检测装置2，也可以设置多个拉曼散射检测装置2，在此不做限定。
具体地，如图8所示，驱动电路001可以具体包括：位于下基板102与第一疏水层105之间的驱动电极103，以及位于上基板101与第二疏水层108之间的参比电极106，以及位于下基板102与驱动电极103所在层之间的开关晶体管，即驱动电路001为有源驱动，开关晶体管可以包括：在下基板102上依次层叠设置的栅极301，栅绝缘层302，有源层303，源漏极304；具体地，栅极301和有源层303的位置也可以互换，在此不做限定。开关晶体管300和驱动电极103所在层之间一般具有第三绝缘层305，源漏极304中的漏极通过贯穿第三绝缘层305的过孔与驱动电极103连接。数字微流控芯片1还可以包括：位于驱动电极103所在层与第一疏水层105之间的第一绝缘层104，位于参比电极106所在层与第二疏水层108之间的第二绝缘层107。
众所周知，拉曼散射是一种快速、无损、特异性强的检测手段，检测时间可短至1秒，不同物质的拉曼光谱图均不相同，是分子的“指纹谱”。因此，覆盖有液滴的驱动电路001的拉曼光谱图与未覆盖有液滴的拉曼光谱图必然不同，因而采用激光头004照射驱动电路001，之后从接收头005获得的散射光谱，通过分析电路对散射光谱进行分析可以实现对液滴位置的定位。
并且，若两个液滴发生反应，生成了新的物质，则停留有单一液滴的驱动电路001的拉曼光谱图必然与停留有两个液滴的驱动电路001的拉曼光谱图不同，通过散射光谱检测，可以获知是否发生反应，即检测反应产物。
综上所述，采用图7所示的数字微流控系统不仅可控制液滴移动，实现液滴定位，还可以检测反应产物，而且成本低，计算量小，高效迅速。
基于同一发明构思，本公开实施例提供了一种上述数字微流控系统的定位方法，如图9所示，包括以下步骤：
S901、控制数字微流控芯片中的液滴在设定路径上移动；
S902、在控制数字微流控芯片中的液滴移动到检测位点之前，采用拉曼散射检测装置中的激光头照射液滴将要移动到的位置后，采用拉曼散射检测装置中的接收头采集拉曼散射光谱；
S903、在控制数字微流控芯片中的液滴移动到检测位点之后，确定接收 头采集到的拉曼散射光谱发生变化，则确定液滴移动到检测位点。
具体地，拉曼散射是一种快速、无损、特异性强的检测手段，检测时间可短至1秒，不同物质的拉曼光谱图均不相同，是分子的“指纹谱”。因此，覆盖有液滴的驱动电路的拉曼光谱图与未覆盖有液滴的拉曼光谱图必然不同，因而采用激光头照射驱动电路，之后从接收头获得的散射光谱，通过分析电路对散射光谱进行分析，即对检测位点的拉曼散射光谱进行监控，可以检测液滴移动的位置，实现液滴位置的定位。
具体地，由于数字微流控系统常被配置为检测生物化学反应，采用本公开实施例提供的上述数字微流控系统除了可以实现控制液滴移动及对液滴位置进行定位之外，还可以实现对反应产物的检测，进一步地，在本公开实施例提供的上述定位方法中，具体地，上述步骤S901控制数字微流控芯片中的液滴在设定路径上移动，具体包括：控制数字微流控芯片中的不同液滴在交叉的至少两条设定路径上移动；
在确定各液滴移动到交叉位置的检测位点并停留预设时间后，在交叉位置及以后的检测位点确定的拉曼散射光谱与交叉位置之前的检测位点确定的拉曼散射光谱不同时，确定各液滴之间在交叉位置发生反应。
具体地，以图7所示的数字微流控系统检测两个液滴的反应为例。可以看出，在图7中，通过给第一预设运动路径上的各驱动电路001，以及第二预设运动路径上的各驱动电路001逐个施加驱动电压，使得两个液滴分别从a口和b口进入第一预设运动路径与第二预设运动路径的交叉点d所在的驱动电路001，且两个液滴在交叉点d所在的驱动电路001上融合并停留预设时间再移动至c口；在此过程中，激光头004按照预设时序照射各驱动电路001。众所周知，拉曼散射是一种快速、无损、特异性强的检测手段，检测时间可短至1秒，不同物质的拉曼光谱图均不相同，是分子的“指纹谱”。因此，若两个液滴发生反应，生成了新的物质，则停留有单一液滴的驱动电路001的拉曼光谱图必然与停留有两个液滴的驱动电路001的拉曼光谱图不同。
综上所述，采用图7所示的数字微流控系统不仅可控制液滴移动，实现 液滴定位，还可以检测反应产物，而且成本低，计算量小，高效迅速。
需要说明的是，在本文中，诸如第一和第二之类的关系术语仅仅用来将一个实体或操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。
显然，本领域的技术人员可以对本公开进行各种改动和变型而不脱离本公开的精神和范围。这样，倘若本公开的这些修改和变型属于本公开权利要求及其等同技术的范围之内，则本公开也意图包含这些改动和变型在内。

Claims (16)

  1. 一种数字微流控芯片，其中，包括：
    相对而置的上基板和下基板；
    第一疏水层，位于所述下基板面向所述上基板一侧表面；
    第二疏水层，位于所述上基板面向所述下基板一侧表面，所述第一疏水层与所述第二疏水层之间的空间构成液滴容置空间；以及，
    多个驱动电路和多个寻址电路，位于所述下基板和所述上基板之间；
    其中，一个所述寻址电路对应至少一个所述驱动电路。
  2. 如权利要求1所述的数字微流控芯片，其中，所述驱动电路包括位于所述下基板与所述第一疏水层之间的驱动电极，以及位于所述上基板与所述第二疏水层之间的参比电极；各所述驱动电路的参比电极相互连接构成一体结构；
    所述数字微流控芯片还包括：位于所述驱动电极所在层与所述第一疏水层之间的第一绝缘层，位于所述参比电极所在层与所述第二疏水层之间的第二绝缘层。
  3. 如权利要求2所述的数字微流控芯片，其中，所述寻址电路包括：位于所述下基板与所述第一疏水层之间层叠设置的底电极、光电转换层和顶电极，其中，所述底电极相对于所述顶电极靠近所述下基板，所述顶电极为透明电极。
  4. 如权利要求3所述的数字微流控芯片，其中，所述顶电极所在层与所述驱动电极所在层为同一膜层。
  5. 如权利要求4所述的数字微流控芯片，其中，所述顶电极与相邻的一个所述驱动电极相互连接构成一体结构。
  6. 如权利要求3所述的数字微流控芯片，其中，所述顶电极所在层位于所述驱动电极所在层面向所述下基板的一侧；所述顶电极在所述下基板的正投影被所述驱动电极在所述下基板的正投影至少部分覆盖。
  7. 如权利要求4至6任一项所述的数字微流控芯片，其中，所述驱动电路还包括：位于所述下基板与所述驱动电极所在层之间的开关晶体管，所述开关晶体管包括：在所述下基板上依次层叠设置的栅极，栅绝缘层，有源层，源漏极；
    所述开关晶体管和所述驱动电极所在层之间具有第三绝缘层，所述源漏极中的漏极通过贯穿所述第三绝缘层的过孔与所述驱动电极连接。
  8. 如权利要求7所述的数字微流控芯片，其中，所述数字微流控芯片还包括：与所述底电极电连接的偏置电压信号线；
    所述底电极与所述源漏极同层设置，所述偏置电压信号线与所述栅极同层设置。
  9. 一种数字微流控系统，其中，包括：如权利要求1-8任一项所述数字微流控芯片，以及控制电路；
    所述控制电路与所述数字微流控芯片中的驱动电路和寻址电路电连接，所述控制电路被配置为在驱动阶段，对各所述驱动电路施加驱动电压，以控制液滴在所述液滴容置空间内按照设定路径移动；在检测阶段，对各所述寻址电路施加偏置电压后，检测各所述寻址电路的电荷损失量，根据所述电荷损失量确定所述液滴的位置；其中，各所述寻址电路的电荷损失量与接收到的外界光线强度相关。
  10. 如权利要求9所述的数字微流控系统，其中，所述控制电路具体被配置为在驱动阶段，根据确定出所述液滴的位置，对设定移动路径上与所述液滴的位置相邻的下一个所述驱动电路施加驱动电压，使所述液滴按照所述设定路径移动。
  11. 如权利要求9所述的数字微流控系统，其中，所述控制电路包括：栅极驱动电路和数据驱动电路；
    所述数字微流控芯片中的各所述开关晶体管的栅极通过同层设置的栅线与所述栅极驱动电路电连接，各开关晶体管的源漏极中的源极通过同层设置的数据线与所述数据驱动电路电连接，各所述偏置电压信号线与所述栅极驱 动电路或所述数据驱动电路电连接。
  12. 一种如权利要求9-11任一项所述的数字微流控系统的驱动方法，其中，包括：
    在驱动阶段，对各所述驱动电路施加驱动电压，以控制液滴在所述液滴容置空间内按照设定路径移动；
    在检测阶段，对各所述寻址电路施加偏置电压后，检测各所述寻址电路的电荷损失量，根据所述电荷损失量确定所述液滴的位置；
    其中，各所述寻址电路的电荷损失量与接收到的外界光线强度相关。
  13. 如权利要求12所述的驱动方法，其中，具体包括：
    在驱动阶段，根据确定出所述液滴的位置，对设定移动路径上与所述液滴的位置相邻的下一个所述驱动电路施加驱动电压，使所述液滴按照所述设定路径移动。
  14. 一种数字微流控系统，其中，包括：
    数字微流控芯片，所述数字微流控芯片包括：相对而置的上基板和下基板，位于所述下基板面向所述上基板一侧表面的第一疏水层，位于所述上基板面向所述下基板一侧表面的第二疏水层，以及位于所述下基板和所述上基板之间的多个驱动电路；其中，所述第一疏水层与所述第二疏水层之间的空间构成液滴容置空间；多个所述驱动电路中的至少部分驱动电路被设置为监测位点；
    拉曼散射检测装置，所述拉曼散射检测装置包括：所述激光头、接收头和分析电路，所述激光头被配置为按预设时序逐个照射各所述监测位点，所述接收头被配置为接收所述监测位点散射光谱，所述分析电路被配置为根据所述接收头反馈的散射光谱确定监测位点是否存在液滴。
  15. 一种数字微流控系统的定位方法，其中，包括：
    控制数字微流控芯片中的液滴在设定路径上移动；
    在控制数字微流控芯片中的液滴移动到检测位点之前，采用拉曼散射检测装置中的激光头照射液滴将要移动到的位置后，采用拉曼散射检测装置中 的接收头采集拉曼散射光谱；
    在控制数字微流控芯片中的液滴移动到检测位点之后，确定所述接收头采集到的拉曼散射光谱发生变化，则确定液滴移动到检测位点。
  16. 如权利要求15所述的定位方法，其中，所述控制数字微流控芯片中的液滴在设定路径上移动，具体包括：
    控制所述数字微流控芯片中的不同液滴在交叉的至少两条设定路径上移动；
    在确定各液滴移动到交叉位置的检测位点并停留预设时间后，在交叉位置及以后的检测位点确定的拉曼散射光谱与交叉位置之前的检测位点确定的拉曼散射光谱不同时，确定各所述液滴之间在交叉位置发生反应。
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