CN111450907B - Microfluidic device, sample mixing method and microfluidic system - Google Patents

Microfluidic device, sample mixing method and microfluidic system Download PDF

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Publication number
CN111450907B
CN111450907B CN202010337805.0A CN202010337805A CN111450907B CN 111450907 B CN111450907 B CN 111450907B CN 202010337805 A CN202010337805 A CN 202010337805A CN 111450907 B CN111450907 B CN 111450907B
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electrode
sample
sub
microfluidic device
lower substrate
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CN111450907A (en
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樊博麟
赵莹莹
古乐
姚文亮
廖辉
高涌佳
李月
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BOE Technology Group Co Ltd
Beijing BOE Sensor Technology Co Ltd
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BOE Technology Group Co Ltd
Beijing BOE Sensor Technology Co Ltd
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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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/05—Mixers using radiation, e.g. magnetic fields or microwaves to mix the material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/305—Micromixers using mixing means not otherwise provided for
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/40—Mixers using gas or liquid agitation, e.g. with air supply tubes
    • B01F33/403—Mixers using gas or liquid agitation, e.g. with air supply tubes for mixing liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/40—Mixers using gas or liquid agitation, e.g. with air supply tubes
    • B01F33/409—Parts, e.g. diffusion elements; Accessories
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • 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

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Abstract

The application discloses a microfluidic device, a sample mixing method and a microfluidic system, which are used for rapidly mixing samples on the microfluidic device and improving the detection efficiency of the microfluidic device. The embodiment of the present application provides a microfluidic device, the microfluidic chip includes: a lower substrate and an upper substrate provided to the cartridge; the lower substrate includes: the lower substrate base plate is positioned on a micro-channel which is positioned on one side of the lower substrate base plate facing the upper substrate and is used for accommodating liquid drops; the upper substrate includes: the upper substrate comprises an upper substrate base plate, a plurality of electrode groups and a dielectric layer, wherein the electrode groups are positioned on one side, facing the lower substrate, of the upper substrate base plate; the orthographic projection of the electrode group falls into the orthographic projection of the micro-channel; the set of electrodes is configured to: and applying a voltage to the electrode group to enable reversible dielectric breakdown of the dielectric layer.

Description

Microfluidic device, sample mixing method and microfluidic system
Technical Field
The application relates to the technical field of microfluidics, in particular to a microfluidic device, a sample mixing method and a microfluidic system.
Background
Microfluidics (Microfluidics) is a technology for precisely controlling and manipulating microscale fluids, by which researchers can integrate basic operational units for sample preparation, reaction, separation, detection, etc. onto a centimeter-scale chip. The microfluidic technology is generally applied to the analysis process of trace drugs in the fields of biology, chemistry, pharmacy and the like, and mainly relates to the uniform mixing, transportation and the like of trace reagents. The uniform mixing of the samples is one of the important steps of biochemical detection, and has important significance for the development of the fields of biological medicine, medical diagnosis, food sanitation, environmental monitoring, molecular biology and the like.
In the existing microfluidic technology, sample mixing is generally completed in external equipment such as a shaker, a centrifuge and the like, which is very unfavorable for the integrated development of the microfluidic chip. If the processes of mixing, incubating and the like of the sample are finished on the microfluidic chip, the concentration gradient or the temperature gradient of the sample is generally utilized to finish the mixing of the sample through the diffusion effect on the premise of not using complex external driving equipment, and compared with an active mixing method, the method has longer mixing time and is not beneficial to improving the detection efficiency of the microfluidic chip.
In conclusion, the prior art cannot rapidly mix the sample on the micro-fluidic chip, and the detection efficiency of the micro-fluidic chip is affected.
Disclosure of Invention
The embodiment of the application provides a microfluidic device, a sample mixing method and a microfluidic system, which are used for rapidly mixing samples on the microfluidic device and improving the detection efficiency of the microfluidic device.
The embodiment of the present application provides a microfluidic device, the microfluidic chip includes: a lower substrate and an upper substrate provided to the cartridge;
the lower substrate includes: the lower substrate base plate is positioned on a micro-channel which is positioned on one side of the lower substrate base plate facing the upper substrate and used for containing liquid drops;
the upper substrate includes: the upper substrate comprises an upper substrate base plate, a plurality of electrode groups and a dielectric layer, wherein the electrode groups are positioned on one side, facing the lower substrate, of the upper substrate base plate;
the orthographic projection of the electrode group falls into the orthographic projection of the micro-channel;
the set of electrodes is configured to: and applying a voltage to the electrode group to enable reversible dielectric breakdown of the dielectric layer.
According to the microfluidic device provided by the embodiment of the application, the dielectric layer and the electrode group are arranged on the upper substrate, and reversible dielectric breakdown can be generated on the dielectric layer by applying voltage to the electrode group, so that bubbles can be generated by electrolyzing liquid drops of a sample to be uniformly mixed in a micro-channel, the sample can be rapidly uniformly mixed by using the stirring effect of the bubbles, the sample uniformly mixing efficiency in the microfluidic device is improved, and the detection efficiency of the microfluidic device is improved.
Optionally, the micro flow channel comprises: the device comprises a main runner extending along a first direction and a plurality of pairs of branch runners intersected with the main runner;
each pair of branch flow passages includes: the first branch flow channel and the second branch flow channel are respectively positioned on two sides of the main flow channel;
the orthographic projection of the electrode group falls into the orthographic projection of the main flow passage.
Optionally, each of the electrode sets includes two first sub-electrodes arranged along a first direction, and one second sub-electrode located between the two first sub-electrodes; the first direction is a direction in which the main flow passage extends.
Optionally, in the first direction, the width of the second sub-electrode is greater than the width of the first sub-electrode.
Optionally, in the first direction, a width of the first sub-electrode and a width of the second sub-electrode are both smaller than a diameter of the droplet; and in the first direction, when the orthographic projection of the center of the liquid drop is superposed with the orthographic projection of the center of the second sub-electrode, the orthographic projection of the liquid drop and the orthographic projections of the two first sub-electrodes are overlapped.
According to the microfluidic device provided by the embodiment of the application, the diameter of the liquid drop is taken into consideration by the size design of each electrode in the electrode group, so that when the central orthographic projection of the liquid drop of a sample to be uniformly mixed is superposed with the central orthographic projection of the second sub-electrode, the liquid drop also covers the area of the first sub-electrode, the dielectric layer of the liquid drop covering area can be ensured to be subjected to point breakdown, and the liquid drop is electrolyzed to generate bubbles so as to uniformly mix the sample.
Optionally, the upper substrate further includes: the first liquid inlet hole, the plurality of second liquid inlet holes, the plurality of third liquid inlet holes and the liquid outlet hole penetrate through the upper substrate;
on the lower substrate base plate, the orthographic projection of the first liquid inlet hole is overlapped with the orthographic projection of the main flow channel in the starting point region of the main flow channel, the liquid outlet hole is overlapped with the orthographic projection of the main flow channel in the terminal region of the main flow channel, and the orthographic projection of the second liquid inlet hole is overlapped with the orthographic projection of the first branch flow channel in the starting point region of the first branch flow channel; and the orthographic projection of the third liquid inlet hole is overlapped with the orthographic projection of the second branch flow channel in the starting point area of the second branch flow channel.
Optionally, the number of the electrode sets is equal to the number of pairs of the branch channels, and each electrode set is located on one side of a pair of the branch channels away from the first liquid inlet hole.
Optionally, the lower substrate further comprises: the first electrode layer is positioned on one side, facing the upper substrate, of the lower substrate and positioned in the micro flow channel; the first electrode layer is at least positioned in the main flow channel.
According to the microfluidic device provided by the application embodiment, the lower substrate is further provided with the first electrode layer, and the first electrode layer and the electrode group are respectively located on two sides of the dielectric layer, so that an electric field which can easily enable the dielectric layer to generate reversible dielectric breakdown can be formed on two sides of the dielectric layer through the first electrode layer and the electrode group. The control of the reversible dielectric breakdown range of the dielectric layer is easier to realize.
Optionally, the microfluidic device further comprises a ground electrode electrically connected to the first electrode layer; the microfluidic device further comprises: and the driving chip is electrically connected with the electrode group.
Optionally, the microfluidic device further comprises: the first optical assembly and the second optical assembly are respectively positioned on two sides of the micro-channel in the plane direction perpendicular to the micro-fluidic device;
the first optical assembly includes: a first optical filter;
the second optical assembly includes: the second optical filter is arranged on the micro-lens array on any side of the second optical filter, and the collimation and planarization layer is arranged on the light inlet side of the micro-lens array;
the orthographic projection of the first optical component and the orthographic projection of the second optical component at least cover the micro-channel.
The micro-fluidic device provided by the embodiment of the application has the advantages that the optical components except the light source and the photoelectric detector for carrying out optical detection on the sample are arranged in the micro-fluidic device, namely the optical components are integrated with the micro-fluidic device, the integration level of the micro-fluidic device is further improved, complex optical alignment is not needed, the optical path can be effectively shortened, and the volume of an optical detection system can be reduced. And because first filter layer and second filter layer are located micro-fluidic device inside, first filter layer and second filter layer are nearer apart from the sample that awaits measuring, and the exciting light that passes through the second light filter is through shorter optical path illumination and sample, improves the exciting light intensity of shining the sample, and the exciting light passband is narrower. The first filter layer is arranged in the microfluidic device, so that the distance between the photoelectric detector and the microfluidic device can be greatly reduced, the photoelectric detector receives a strong fluorescent signal, the strength of a detection signal can be improved, and the detection accuracy is improved.
Optionally, the second optical assembly further comprises: an anti-reflective layer between the microlens array and the collimating planarizing layer.
According to the micro-fluidic device provided by the embodiment of the application, the anti-reflection layer is further arranged between the collimation planarization layer and the micro-lens array, so that the reflection generated when light reaches different sections can be reduced, the light loss is reduced, the intensity of a light signal irradiating a sample is improved, the intensity of a fluorescence signal of the sample during departure is improved, and the detection accuracy is improved.
Optionally, the first optical component is located between the lower substrate base plate and the first electrode layer; or the first optical assembly is positioned on one side of the first electrode layer, which is far away from the lower substrate; or the first optical assembly is positioned on one side of the lower substrate base plate, which is far away from the upper substrate base plate;
the second optical assembly is positioned on one side of the upper substrate base plate, which is far away from the lower substrate base plate; alternatively, the second optical assembly is located between the upper substrate base plate and the electrode set; or the second optical assembly is positioned on one side of the electrode group, which is far away from the lower substrate, and the upper substrate is positioned between the second optical filter and the micro-lens array.
Optionally, the first optical assembly is located between the upper substrate base plate and the electrode set; or the first optical assembly is positioned on one side of the upper substrate base plate, which is far away from the lower substrate base plate;
the second optical assembly is positioned on one side of the lower substrate base plate, which is far away from the upper substrate base plate; or the second optical assembly is positioned on one side of the lower substrate base plate facing the upper substrate base plate; or, the lower substrate base plate is positioned between the micro-lens array and the second optical filter.
The embodiment of the application provides a sample mixing method using the microfluidic device, and the method comprises the following steps:
in the first stage, a driving liquid, a first sample and a second sample to be mixed are introduced into the micro-channel, and the driving liquid is used for driving the droplets to be mixed, which are composed of the first sample and the second sample, to move towards the electrode group;
in the second stage, when the orthographic projection of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the electrode group, voltage is loaded on the electrode group, and the liquid drop to be uniformly mixed is driven to move;
and in the third stage, when the liquid drop to be uniformly mixed is coincident with the center of the electrode group, stopping introducing the driving liquid, adjusting the voltage loaded on the electrode group to enable the dielectric layer to generate reversible dielectric breakdown, and enabling the liquid drop to be uniformly mixed to be electrolyzed to generate bubbles so as to uniformly mix the first sample and the second sample in the liquid drop to be uniformly mixed.
The sample mixing method provided by the embodiment of the application is carried out in a microfluidic device, firstly, a driving liquid is used for driving a liquid drop to be mixed to move towards an electrode group, then, when the liquid drop moves to an area covered by the electrode group, the electrode group is used for driving the liquid drop to be mixed to coincide with the center of the electrode group, then, voltage is applied to the electrode group so that reversible dielectric breakdown occurs to a dielectric layer, and therefore the liquid drop of the sample to be mixed in a micro-channel can be electrolyzed to generate bubbles, the stirring effect of the bubbles is used for realizing the rapid mixing of the sample, the sample mixing efficiency in the microfluidic device is improved, and the detection efficiency of the microfluidic device is improved. In addition, the sample mixing method provided by the embodiment of the application combines a micro-channel mode of driving liquid drops to move by using driving liquid and a digital micro-fluidic mode of driving the liquid drops, so that the method has the advantages of high control efficiency of a channel type micro-fluidic device, large control flux of the liquid drops and high control precision of the digital micro-fluidic device.
Optionally, the method of introducing a driving liquid, a first sample to be mixed uniformly, and a second sample into the micro flow channel specifically includes:
and continuously introducing a driving liquid into the main flow channel, introducing a first sample into the first branch flow channel and introducing a second sample into the second branch flow channel after the main flow channel is filled with the driving liquid, and continuously introducing the driving liquid so as to separate the first sample and the second sample from the branch flow channel when the first sample and the second sample flow to the intersection region of the branch flow channel and the main flow channel.
Optionally, when the orthographic projection of the droplet to be mixed is overlapped with the orthographic projection of the electrode group, applying a voltage to the electrode group specifically includes:
before the orthographic projection of the center of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the center of the second sub-electrode, loading a first voltage signal to the first sub-electrode and the second sub-electrode in sequence so as to enable the liquid drop to be uniformly mixed to move along the main runner.
Optionally, the lower substrate includes a first electrode layer, the first electrode layer is electrically connected to a ground potential, and when the droplet to be mixed coincides with the center of the electrode group, the voltage applied to the electrode group is adjusted, which specifically includes:
and applying a second voltage signal to the first sub-electrode to enable the potential of the first sub-electrode relative to the first electrode layer to be 0, and applying a third voltage signal to the second sub-electrode to enable the potential difference between the second sub-electrode and the first sub-electrode to be not less than the dielectric layer reversible dielectric breakdown critical voltage.
Optionally, after the third stage, the method further comprises:
and in the fourth stage, after the preset duration of voltage loading on the electrode group is finished, the voltage application on the electrode group is stopped, the driving liquid is continuously introduced, and the uniformly mixed liquid drops are driven to flow out from the liquid outlet.
The microfluidic system provided by the embodiment of the application comprises the microfluidic device provided by the embodiment of the application.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a microfluidic device provided in an embodiment of the present application;
fig. 2 is a top view of a substrate under a microfluidic device according to an embodiment of the present disclosure;
fig. 3 is a top view of a substrate on a microfluidic device according to an embodiment of the present disclosure;
fig. 4 is a top view of a microfluidic device provided in an embodiment of the present application;
fig. 5 is a schematic structural diagram of another microfluidic device provided in an embodiment of the present application;
fig. 6 is a schematic structural diagram of a lower substrate of a microfluidic device according to an embodiment of the present disclosure;
fig. 7 is a schematic structural diagram of a lower substrate of another microfluidic device provided in an embodiment of the present application;
fig. 8 is a schematic structural diagram of an upper substrate of a microfluidic device according to an embodiment of the present disclosure;
fig. 9 is a schematic structural diagram of an upper substrate of another microfluidic device provided in an embodiment of the present application;
fig. 10 is a schematic structural diagram of an upper substrate of a microfluidic device according to an embodiment of the present disclosure;
fig. 11 is a schematic structural diagram of an upper substrate of another microfluidic device provided in an embodiment of the present application;
fig. 12 is a schematic structural diagram of an upper substrate of another microfluidic device provided in an embodiment of the present application;
fig. 13 is a schematic structural diagram of another microfluidic device provided in an embodiment of the present application;
fig. 14 is a schematic structural diagram of an upper substrate of another microfluidic device provided in an embodiment of the present application;
fig. 15 is a schematic structural diagram of a lower substrate of a further microfluidic device provided in an embodiment of the present application;
fig. 16 is a schematic structural diagram of a lower substrate of yet another microfluidic device provided in an embodiment of the present application;
fig. 17 is a schematic structural diagram of a lower substrate of a further microfluidic device provided in an embodiment of the present application;
fig. 18 is a schematic structural diagram of a lower substrate of another microfluidic device provided in an embodiment of the present application;
fig. 19 is a schematic structural diagram of a lower substrate of another microfluidic device provided in an embodiment of the present application;
fig. 20 is a schematic structural diagram of a lower substrate of a further microfluidic device provided in an embodiment of the present application;
fig. 21 is a schematic structural diagram of a lower substrate of yet another microfluidic device provided in an embodiment of the present application;
fig. 22 is a schematic structural diagram of a lower substrate of a further microfluidic device provided in an embodiment of the present application;
fig. 23 is a schematic structural diagram of a lower substrate of yet another microfluidic device provided in an embodiment of the present application;
fig. 24 is a schematic structural diagram of a lower substrate of yet another microfluidic device provided in an embodiment of the present application;
fig. 25 is a schematic structural diagram of a lower substrate of yet another microfluidic device provided in an embodiment of the present application;
FIG. 26 is a schematic diagram of a sample blending method according to an embodiment of the present disclosure;
fig. 27 and 28 are schematic diagrams of a microfluidic device simulation provided in an embodiment of the present application;
fig. 29 is a graph simulating reversible dielectric breakdown electric field distribution of the microfluidic device corresponding to fig. 27 provided in an embodiment of the present application;
fig. 30 is a graph illustrating simulation of distribution of reversible dielectric breakdown electric fields of the microfluidic device corresponding to fig. 28 according to an embodiment of the present disclosure.
Detailed Description
An embodiment of the present application provides a microfluidic device, as shown in fig. 1, where the microfluidic chip includes: a lower substrate 1 and an upper substrate 2 provided to the cartridge;
the lower substrate 1 includes: a lower substrate 3, a micro flow channel 4 for containing liquid drops and located on one side of the lower substrate 3 facing the upper substrate 2;
the upper substrate 2 includes: the structure comprises an upper substrate 5, a plurality of electrode groups 6 positioned on one side of the upper substrate 5 facing the lower substrate 1, and a dielectric layer 7 positioned on one side of the electrode groups 6 facing the lower substrate 1;
the orthographic projection of the electrode group 6 falls into the orthographic projection of the micro flow channel 4;
the electrode group 6 is configured to: a voltage is applied to the electrode assembly 6 to cause reversible dielectric breakdown of the dielectric layer 7.
It should be noted that, in the microfluidic device provided in the embodiment of the present application, a voltage is applied to the electrode group to cause a dielectric breakdown of the dielectric layer, where the dielectric breakdown is an electrical breakdown and is a reversible non-destructive dielectric breakdown. The dielectric layer is an insulator when dielectric breakdown does not occur, the dielectric breakdown is changed into a conductor when the dielectric breakdown occurs, the sample liquid drop to be uniformly mixed usually comprises electrolytic electrolyte, and when the dielectric breakdown occurs in the dielectric layer, bubbles are generated by the liquid drop electrolysis, so that the rapid, high-flux controllable and active uniform mixing of the sample to be uniformly mixed can be realized by utilizing the stirring effect of the bubbles.
According to the microfluidic device provided by the embodiment of the application, the dielectric layer and the electrode group are arranged on the upper substrate, and reversible dielectric breakdown can be generated on the dielectric layer by applying voltage to the electrode group, so that bubbles can be generated by electrolyzing liquid drops of a sample to be uniformly mixed in a micro-channel, the sample can be rapidly uniformly mixed by using the stirring effect of the bubbles, the sample uniformly mixing efficiency in the microfluidic device is improved, and the detection efficiency of the microfluidic device is improved.
In fig. 1, the substance filling the micro flow channel 4 includes the droplet 17 to be mixed and the driving liquid 29.
Optionally, the set of electrodes is further configured to: a voltage is applied to the set of electrodes to cause the droplet to move. The microfluidic device provided by the embodiment of the application comprises a microchannel and an electrode group, namely, the microchannel microfluidic device is combined with a digital microfluidic device, and a driving liquid can be used for driving liquid drops to move and the electrode group can be used for controlling the liquid drops to move, so that the microfluidic device has the advantages of high control efficiency of the channel microfluidic device, large control flux of the liquid drops and high control precision of the digital microfluidic device.
Optionally, as shown in fig. 2 and 3, the micro flow channel includes: a main flow passage 11 extending in a first direction, and a plurality of pairs of branch flow passages 12 intersecting the main flow passage 11;
each pair of the branched flow paths 12 includes: a first branch flow channel 13 and a second branch flow channel 14 respectively located at both sides of the main flow channel 11;
the orthographic projection of the electrode group 6 falls within the orthographic projection of the primary channel 11.
The orthographic projection of the electrode group falls into the orthographic projection of the main flow channel, namely the sample is uniformly mixed in the main flow channel area.
Optionally, as shown in fig. 3 and 4, the upper substrate 2 further includes: a first liquid inlet hole 18, a plurality of second liquid inlet holes 19, a plurality of third liquid inlet holes 20 and a liquid outlet hole 21 which penetrate through the upper substrate base plate;
on the lower substrate base plate 3, an orthographic projection of the first liquid inlet hole 18 overlaps with an orthographic projection of the main flow passage 11 at a starting point region of the main flow passage 11, the liquid outlet hole 21 overlaps with an orthographic projection of the main flow passage 11 at a terminal point region of the main flow passage 11, and an orthographic projection of the second liquid inlet hole 19 overlaps with an orthographic projection of the first branch flow passage 13 at a starting point region of the first branch flow passage 13; the orthographic projection of the third liquid inlet hole 20 overlaps with the orthographic projection of the second branch flow channel 14 at the starting point area of the second branch flow channel 14.
Fig. 2 is a projection view of the microchannel onto the lower substrate, fig. 3 is a projection view of the microchannel, each of the liquid inlet holes and the liquid outlet holes, and the electrode group onto the lower substrate, and fig. 4 is a projection view of each of the liquid inlet holes and the liquid outlet holes, and the electrode group onto the upper substrate. Fig. 1 may be, for example, a cross-sectional view along AA' in fig. 3. The microfluidic device shown in fig. 2 to 4 provided in the embodiment of the present application is exemplified by taking an example that the main channel and the branch channels are both strip-shaped, and each pair of branch channels and the main channel are perpendicular to each other, and the microfluidic device includes eight pairs of branch channels and eight electrode groups. In fig. 3 and 4, the diameters of the first liquid inlet hole and the liquid outlet hole are equal, the diameters of the second liquid inlet hole and the third liquid inlet hole are equal, and the diameters of the first liquid inlet hole and the second liquid inlet hole are not equal. The diameters of the first liquid inlet hole, the second liquid inlet hole, the third liquid inlet hole and the third liquid inlet hole can be selected according to actual needs.
When the micro-channel device provided by the embodiment of the application is used for uniformly mixing samples, the driving liquid can be introduced into the first liquid inlet hole corresponding to the main channel, the liquid drop of the first sample can be introduced into the second liquid inlet hole, the liquid drop of the second sample can be introduced into the third liquid inlet hole, the liquid drop of the first sample and the liquid drop of the second sample can be converged in the main channel to obtain the liquid drop to be uniformly mixed, the liquid drop to be uniformly mixed can flow along the main channel under the driving of the driving liquid, when the liquid drop moves to the electrode group, the electrode group can be electrified, the liquid drop movement is controlled to enable the center of the liquid drop and the center of the second sub-electrode to be located on the same straight line, then, the voltage is applied to the electrode group to enable the dielectric layer to generate reversible dielectric breakdown, the dielectric layer is changed from an insulator to a conductor, and the electrolyte in the liquid drop to be uniformly mixed is electrolyzed to generate bubbles, so that the first sample and the second sample in the liquid drop to be uniformly mixed can be rapidly mixed.
Optionally, as shown in fig. 4, the number of the electrode sets 6 is equal to the number of pairs of the branch channels 12, and each electrode set 6 is located on one side of a pair of the branch channels 12 away from the first liquid inlet hole 18.
Therefore, the reversible dielectric breakdown of the dielectric layer can be generated after the sample to be mixed is converged to obtain the liquid drop to be mixed.
Alternatively, as shown in fig. 1, 3 and 4, each of the electrode groups 6 includes two first sub-electrodes 15 arranged along the first direction X, and one second sub-electrode 16 located between the two first sub-electrodes 15; the first direction X is a direction in which the main flow passage 11 extends.
Optionally, as shown in fig. 1 and 3, in the first direction X, the width of the second sub-electrode 16 is greater than the width of the first sub-electrode 15.
Alternatively, as shown in fig. 1, in the first direction X, the width of the first sub-electrode 15 and the width of the second sub-electrode 16 are both smaller than the diameter of the droplet 17; and in the first direction X, when the orthographic projection of the center of the liquid drop 17 is overlapped with the orthographic projection of the center of the second sub-electrode 16, the orthographic projection of the liquid drop 17 is overlapped with the orthographic projections of the two first sub-electrodes 15.
It should be noted that, when the droplets to be mixed only cover the second sub-electrode, the potential difference between the two sides of the dielectric layer in the area covered only by the second sub-electrode is relatively small, and the situation that the potential difference cannot reach the click-through critical voltage of the dielectric layer is likely to occur, so that the dielectric layer in the area cannot be subjected to reversible dielectric breakdown, and the droplets to be mixed cannot be electrolyzed to generate bubbles. According to the microfluidic device provided by the embodiment of the application, the diameter of the liquid drop is taken into consideration by the size design of each electrode in the electrode group, so that when the central orthographic projection of the liquid drop of a sample to be uniformly mixed is superposed with the central orthographic projection of the second sub-electrode, the liquid drop also covers the area of the first sub-electrode, the dielectric layer of the liquid drop covering area can be ensured to be subjected to point breakdown, and the liquid drop is electrolyzed to generate bubbles so as to uniformly mix the sample.
Optionally, as shown in fig. 4, the number of the electrode sets 6 is equal to the number of pairs of the branch channels 12, and each electrode set 6 is located on one side of a pair of the branch channels 12 away from the first liquid inlet hole 18.
In specific implementation, the depth of the micro flow channel may be, for example, 100 micrometers (μm), the width of the main flow channel may be, for example, 300 μm, and the width of the branch flow channel may be, for example, 210 μm. The diameters of the first liquid inlet hole, the second liquid inlet hole, the third liquid inlet hole and the liquid outlet hole may be the same, the diameters of the first liquid inlet hole, the second liquid inlet hole, the third liquid inlet hole and the liquid outlet hole may be larger than the width of the micro flow channel, and the diameters of the first liquid inlet hole, the second liquid inlet hole, the third liquid inlet hole and the liquid outlet hole may be 600 μm, for example. The shape of the second sub-electrode may be, for example, a square, the length and width of the second sub-electrode may be, for example, 300 μm, the long side dimension of the second sub-electrode may be, for example, 300 μm, the short side dimension may be, for example, 100 μm, the interval between the first sub-electrode and the second sub-electrode may be, for example, 5 μm, and the thickness of the first sub-electrode and the second sub-electrode may be, for example, 300 nanometers (nm). The thickness of the dielectric layer may be, for example, 1.5 μm. The material of the electrode assembly may comprise, for example, a metal. The material of the dielectric layer may include, for example, a resin.
Optionally, as shown in fig. 1, the lower substrate 1 further includes: a first electrode layer 8 located on one side of the lower substrate 3 facing the upper substrate 2 and located in the microchannel; the first electrode layer is at least located in the main runner.
It should be noted that, the occurrence of the electrical breakdown of the dielectric layer requires that the potential difference between the two sides of the dielectric layer is not less than the electrical breakdown critical value thereof. When the reversible dielectric breakdown of the dielectric layer is realized only by using the electrode group, a larger voltage needs to be applied to the second sub-electrode, and the requirement on a power supply of the microfluidic device is higher. In the microfluidic device provided by the embodiment of the application, the lower substrate is further provided with the first electrode layer, and the first electrode layer and the electrode group are respectively located on two sides of the dielectric layer, so that electric fields which easily enable the dielectric layer to generate reversible dielectric breakdown can be formed on two sides of the dielectric layer through the first electrode layer and the electrode group. The control of the reversible dielectric breakdown range of the dielectric layer is easier to realize.
Optionally, the microfluidic device further comprises a ground electrode electrically connected to the first electrode layer; the microfluidic device further comprises: and the driving chip is electrically connected with the electrode group.
As shown in fig. 1, in the microfluidic device provided in the embodiment of the present application, the lower substrate 1 further includes a first hydrophobic layer 9, and the upper substrate 2 further includes a second hydrophobic layer 10.
In a specific implementation, the thickness of the first electrode layer may be, for example, 300nm, and the thicknesses of the first hydrophobic layer and the second hydrophobic layer may be, for example, 60 nm.
In specific implementation, for the preparation of the lower substrate, for example, the lower substrate may be subjected to a patterning process to form a pattern of a micro channel on the lower substrate, and then a first electrode layer and a first hydrophobic layer are sequentially formed in the micro channel. For the preparation of the upper substrate, for example, an electrode group may be formed on the upper substrate, then a dielectric layer and a second hydrophobic layer are sequentially formed, and then a first liquid inlet, a second liquid inlet, a third liquid inlet and a liquid outlet are formed. The prepared upper substrate and lower substrate are matched with a box to form the microfluidic device provided by the embodiment of the application.
It should be noted that, in the microfluidic device provided in the prior art, when the sample needs to be detected after the automatic preparation, the uniform mixing and the manipulation of the sample are completed, the sample generally needs to be detected by means of a separate external device such as a microscope, a spectrometer and the like, which is not favorable for the integrated development of the microfluidic device. The general biological detection optical system is mostly built by complex space optical components, including: the optical detection system comprises a light source, a light beam collimating lens, an excitation optical filter, a dichroic mirror, an emission optical filter and the like, the optical detection system is large in size, the optical path optical length is long, strong excitation light intensity is needed to offset light intensity attenuation, and the sensitivity of a detector is needed to be improved to collect small detection signals. The complex design increases the requirement of product fineness degree to a certain extent, improves the difficulty of process manufacturing, and increases the complexity of hardware and manufacturing cost.
Optionally, as shown in fig. 5 to 25, the microfluidic device further includes: a first optical assembly 22 and a second optical assembly 23 respectively positioned at two sides of the micro flow channel 4 in a direction perpendicular to the plane of the micro flow control device;
the first optical assembly 22 includes: a first filter 24;
the second optical component 23 comprises: a second optical filter 25, a Micro-lens array (Micro-lenses) 26 located on either side of the second optical filter 25, and a collimation planarization layer 27 located on the light incident side of the Micro-lens array 26;
the orthographic projection of the first optical component 22 and the orthographic projection of the second optical component 23 cover at least the micro flow channel 4.
It should be noted that, when a sample in the microfluidic device provided in the embodiment of the present application is detected, a light source and a photodetector need to be further provided, the light source and the detector are respectively located at two sides of the microfluidic device, an excitation light beam emitted by the light source irradiates the sample to emit fluorescence, and the fluorescence emitted by the sample reaches the photodetector to realize detection of the sample. In the microfluidic device provided by the embodiment of the application, the collimation planarization layer and the microlens array perform shaping and collimation on light emitted by the light source. The second optical filter only enables exciting light emitted by the light source to effectively pass through, and light rays of an external fluorescence wave band are prevented from entering the microfluidic device. The first filter further filters out excitation light and other stray light, so that the detector can obtain a purer fluorescence signal.
According to the micro-fluidic device provided by the embodiment of the application, the optical components for performing optical detection on the sample except for the light source and the photoelectric detector are arranged in the micro-fluidic device, namely the optical components are integrated with the micro-fluidic device, under the condition that the micro-fluidic device can realize rapid and uniform mixing of the sample, the integration level of the micro-fluidic device is further improved, the application of the micro-fluidic device is further increased, complex optical alignment is not needed, the optical path can be effectively shortened, and the volume of an optical detection system can be reduced. And because first filter layer and second filter layer are located micro-fluidic device inside, first filter layer and second filter layer are nearer apart from the sample that awaits measuring, and the exciting light that passes through the second light filter is through shorter optical path illumination and sample, improves the exciting light intensity of shining the sample, and the exciting light passband is narrower. The first filter layer is arranged in the microfluidic device, so that the distance between the photoelectric detector and the microfluidic device can be greatly reduced, the photoelectric detector receives a strong fluorescent signal, the strength of a detection signal can be improved, and the detection accuracy is improved.
Optionally, as shown in fig. 5, the second optical assembly 23 further includes: an anti-reflection layer 28 located between the microlens array 26 and the collimation planarization layer 27.
According to the micro-fluidic device provided by the embodiment of the application, the anti-reflection layer is further arranged between the collimation planarization layer and the micro-lens array, so that the reflection generated when light reaches different sections can be reduced, the light loss is reduced, the intensity of a light signal irradiating a sample is improved, the intensity of a fluorescence signal of the sample during departure is improved, and the detection accuracy is improved.
When the microfluidic device comprises the first optical assembly and the second optical assembly, the upper substrate base plate, the lower substrate base plate, the electrode group, the dielectric layer, the first hydrophobic layer, the second hydrophobic layer and the first electrode layer are made of transparent materials. The material of the electrode group and the first electrode layer may be, for example, Indium Tin Oxide (ITO). The collimating and planarizing layer and the anti-reflection layer may be made of an optically transparent material having a low refractive index, for example, 1.2 to 1.4, a low refractive index polysiloxane material, for example, and the thickness of the collimating and planarizing layer and the anti-reflection layer may be in the order of micrometers, for example. Micro lens can select high refractive index optically transparent material, the refractive index can be 1.7 ~ 1.8 for example, such as high refractive index polysiloxane material, its thickness can be micron order for example. First and second filter layers for filtering lightIn different paragraphs, the materials of the first and second optical filters may be selected from the following materials: silicon oxide (SiO)2) Titanium oxide (TiO)2) Silver (Ag), aluminum (Al), the thickness of the first optical filter and the second optical filter may be, for example, a nanometer scale.
It should be noted that the first optical assembly is disposed on the substrate near the photodetector, and the second optical assembly is disposed on the substrate near the light source. For example, when the photodetector is located on the side of the lower substrate facing away from the upper substrate, the lower substrate comprises the first optical element and the upper substrate comprises the second optical element, and conversely, when the photodetector is located on the side of the upper substrate facing away from the lower substrate, the upper substrate comprises the first optical element and the lower substrate comprises the second optical element.
When the lower substrate comprises the first optical component, optionally, as shown in fig. 5, the first optical component 22 is located on a side of the first electrode layer 8 facing away from the lower substrate 3; alternatively, as shown in fig. 6, the first optical component 22 is located between the lower substrate base plate 3 and the first electrode layer 8; alternatively, as shown in fig. 7, the first optical component 22 is located on the side of the lower substrate 3 away from the upper substrate 5; note that the micro flow channel is not shown in fig. 6 and 7.
When the upper substrate comprises the second optical component, optionally, as shown in fig. 5 and 8, the second optical component 23 is located on the side of the upper substrate 5 facing away from the lower substrate 3;
alternatively, as shown in fig. 9 and 10, the second optical assembly 23 is located between the upper substrate 5 and the electrode group 6;
or the second optical assembly is positioned on one side of the electrode group, which is far away from the lower substrate, and the upper substrate is positioned between the second optical filter and the micro-lens array; as shown in fig. 11, the second optical filter 25 is located between the upper substrate 5 and the electrode set 6, and the microlens array 26 is located on a side of the upper substrate 5 away from the second optical filter 25; as shown in fig. 12, the microlens array 26 is located between the upper substrate 5 and the electrode group 6, the collimating and planarizing layer 27 is located between the microlens array 26 and the upper substrate 5, and the second filter 25 is located on a side of the upper substrate 5 facing away from the microlens array 26.
When the lower substrate includes the first optical device and the upper substrate includes the second optical device, the lower substrate of fig. 5 to 7 may be freely combined with the upper substrate of fig. 5, 8 to 12. In fig. 8, 10, and 12, the second filter is located at the light incident side of the microlens array, and in fig. 5, 9, and 11, the second filter is located at the light emergent side of the microlens array.
Compared with other schemes, the microfluidic device shown in fig. 5 provided by the embodiment of the application has the advantages that the first optical filter is closer to the micro-channel, so that the first optical filter is closer to a sample to be detected, the photoelectric detector can receive stronger fluorescent signals, the intensity of detection signals can be improved, and the detection accuracy is improved.
When the upper base plate comprises a first optical component, optionally, as shown in fig. 13, said first optical component 22 is located between said upper substrate base plate 5 and said electrode set 6; alternatively, as shown in fig. 14, the first optical component 22 is located on the side of the upper substrate 5 facing away from the lower substrate 3.
In the microfluidic device shown in fig. 13 provided in the embodiment of the present application, the first optical filter is closer to the microchannel, so that the first optical filter is closer to the sample to be detected, and thus the photodetector can receive a stronger fluorescence signal, the intensity of the detection signal can be improved, and the detection accuracy can be improved.
When the lower substrate includes the second optical component, optionally, as shown in fig. 13 and fig. 15, the second optical component 23 is located on a side of the lower substrate 3 facing away from the upper substrate 5;
or the second optical assembly is positioned on one side of the lower substrate base plate facing the upper substrate base plate; as shown in fig. 16 and 17, the second optical component 23 is located between the lower substrate 3 and the first electrode layer 8; as shown in fig. 18, 19, the second optical component 23 is located between the first electrode layer 8 and the first hydrophobic layer 9; as shown in fig. 20, the second filter 25 is located between the first electrode layer 8 and the first hydrophobic layer 9, the microlens array 26 is located between the first electrode layer 8 and the lower substrate 3, and the collimation planarization layer 27 is located between the microlens array 26 and the lower substrate 3; as shown in fig. 21, a microlens array 26 is located between the first electrode layer 8 and the first hydrophobic layer 9, a collimation planarization layer 27 is located between the microlens array 26 and the first electrode layer 8, and a second filter 25 is located between the first electrode layer 8 and the lower substrate 3;
or the lower substrate base plate is positioned between the micro-lens array and the second optical filter; as shown in fig. 22, the second filter 25 is located between the lower substrate base plate 3 and the first electrode layer 8, and the microlens array 26 is located on the side of the lower substrate base plate 3 away from the first electrode layer 8; as shown in fig. 23, the microlens array 26 is located between the lower substrate base plate 3 and the first electrode layer 8, the collimation planarization layer 27 is located between the microlens array 26 and the lower substrate base plate 3, and the second filter 25 is located on the side of the lower substrate base plate 3 away from the first electrode layer 8; as shown in fig. 24, the second filter 25 is located between the first electrode layer 8 and the first hydrophobic layer 9, and the microlens array 26 is located on the side of the lower substrate 3 facing away from the first electrode layer 8; as shown in fig. 25, the second filter 25 is located between the first electrode layer 8 and the first hydrophobic layer 9, and the microlens array 26 is located on the side of the lower substrate 3 facing away from the first electrode layer 8.
The micro flow channel is not shown in fig. 13, 15 to 25.
When the upper substrate includes the first optical device and the lower substrate includes the second optical device, the upper substrate of fig. 13 to 14 may be freely combined with the lower substrate of fig. 13, 15 to 25. In fig. 15, 16, 19, 21, 23, and 25, the second filter is located on the light incident side of the microlens array, and in fig. 13, 17, 18, 20, 22, and 24, the second filter is located on the light emergent side of the microlens array.
Based on the same inventive concept, an embodiment of the present application further provides a method for uniformly mixing a sample by using the microfluidic device, as shown in fig. 26, where the method includes:
s101, in the first stage, introducing a driving liquid, a first sample and a second sample to be mixed into the micro-channel, and driving droplets to be mixed, which are formed by the first sample and the second sample, to move towards the electrode group by using the driving liquid;
s102, in the second stage, when the orthographic projection of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the electrode group, voltage is loaded on the electrode group, and the liquid drop to be uniformly mixed is driven to move;
and S103, in the third stage, when the liquid drop to be mixed is coincident with the center of the electrode group, stopping introducing the driving liquid, adjusting the voltage loaded on the electrode group to enable the dielectric layer to generate reversible dielectric breakdown, and enabling the liquid drop to be mixed to be electrolyzed to generate bubbles so as to uniformly mix the first sample and the second sample in the liquid drop to be mixed.
The sample mixing method provided by the embodiment of the application is carried out in a microfluidic device, firstly, a driving liquid is used for driving a liquid drop to be mixed to move towards an electrode group, then, when the liquid drop moves to an area covered by the electrode group, the electrode group is used for driving the liquid drop to be mixed to coincide with the center of the electrode group, then, voltage is applied to the electrode group so that reversible dielectric breakdown occurs to a dielectric layer, and therefore the liquid drop of the sample to be mixed in a micro-channel can be electrolyzed to generate bubbles, the stirring effect of the bubbles is used for realizing the rapid mixing of the sample, the sample mixing efficiency in the microfluidic device is improved, and the detection efficiency of the microfluidic device is improved. In addition, the sample mixing method provided by the embodiment of the application combines a micro-channel mode of driving liquid drops to move by using driving liquid and a digital micro-fluidic mode of driving the liquid drops, so that the method has the advantages of high control efficiency of a channel type micro-fluidic device, large control flux of the liquid drops and high control precision of the digital micro-fluidic device.
It should be noted that when the draw solution is selected, it is ensured that the first sample and the second sample and the mixed solution thereof are insoluble in the draw solution, and the draw solution may be, for example, oil or silicone oil.
Optionally, the method includes introducing a driving liquid, a first sample to be mixed uniformly, and a second sample into the micro flow channel, and specifically includes:
and continuously introducing a driving liquid into the main runner, introducing a first sample into the first branch runner and introducing a second sample into the second branch runner after the main runner is filled with the driving liquid, and continuously introducing the driving liquid so as to separate the first sample and the second sample from the branch runners when the first sample and the second sample flow to the intersection region of the branch runners and the main runner.
Namely, the driving liquid is continuously introduced, and the shearing force of the driving liquid is utilized to complete the separation of the first sample and the first branch flow channel and the separation of the second sample and the second branch flow channel. When the specific implementation is carried out, the first sample and the second sample are stopped to be introduced into the first branch flow channel and the second branch flow channel when the first sample and the second sample reach the preset volume.
Optionally, when the orthographic projection of the droplet to be mixed is overlapped with the orthographic projection of the electrode group, applying a voltage to the electrode group specifically includes:
before the orthographic projection of the center of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the center of the second sub-electrode, loading a first voltage signal to the first sub-electrode and the second sub-electrode in sequence so as to enable the liquid drop to be uniformly mixed to move along the main runner.
Namely, the movement of the liquid drops to be uniformly mixed is controlled by simultaneously utilizing the dielectric wetting effect and the pushing effect of the driving liquid on the liquid drops to be uniformly mixed.
In particular, a voltage of 30 volts (V) may be applied to the electrode assembly.
Optionally, the lower substrate includes a first electrode layer, the first electrode layer is electrically connected to a ground potential, and when the droplet to be mixed coincides with the center of the electrode group, the voltage applied to the electrode group is adjusted, which specifically includes:
and loading a second voltage signal to the first sub-electrode and loading a third voltage signal to the second sub-electrode so as to enable the potential difference at two sides of the dielectric layer not to be less than the reversible dielectric breakdown critical voltage of the dielectric layer.
In specific implementation, the electric breakdown critical voltage of each dielectric is a fixed value, and the electric field distribution of the microfluidic device is simulated by taking the material of the dielectric layer as the resin as an example, wherein the electric breakdown critical voltage of the resin is about233 kilovolts/centimeter (kV/cm). Line ab in fig. 27-28 represents the distance between the first sub-electrode and the second sub-electrode, it should be noted that the length of line ab in fig. 27 is greater than the length of line ab in fig. 28, the microfluidic device in fig. 27 further covers the first sub-electrodes located at both sides of the second sub-electrode when the center of the droplet to be mixed coincides with the orthographic projection of the center of the second sub-electrode, and the microfluidic device in fig. 28 does not cover the first sub-electrode when the center of the droplet to be mixed coincides with the orthographic projection of the center of the second sub-electrode. The electric field distribution of the microfluidic device corresponding to the length of line ab in fig. 27 is shown in fig. 29, and the electric field distribution of the microfluidic device corresponding to the length of line ab in fig. 28 is shown in fig. 30. Points a and B in fig. 29 to 30 represent points respectively located on the upper and lower surfaces of the dielectric layer on the same straight line perpendicular to the dielectric layer. As can be seen from the simulation, as shown in FIG. 29, the potential difference U is present between the two sides of the dielectric layerABWhen the first electrode layer is grounded, the potential difference U between the two sides of the dielectric layer is equal to 60V, and the electric field distribution of the microfluidic device is simulated to obtain a critical value of 32V, wherein the third voltage signal is 60V and the second voltage signal is 0 in the schemeAB32V. As shown in FIG. 30, when the droplets to be mixed only cover the second sub-electrode, the potential difference U between the two sides of the medium layerABRelatively small, UABThe critical voltage for dielectric layer electrical breakdown cannot be reached at 20V.
Optionally, after the third stage, the method further comprises:
and in the fourth stage, after the preset duration of voltage loading on the electrode group, stopping applying voltage on the electrode group, continuously introducing the driving liquid, and driving the uniformly mixed liquid drops to flow out from the liquid outlet.
Next, taking the example that the microfluidic device includes the first electrode layer, and the first electrode layer is grounded, the sample blending method provided in the embodiment of the present application is exemplified.
S201, controlling the electrode group to be powered off, continuously introducing a driving liquid into a main flow channel, introducing a first sample into a first branch flow channel and introducing a second sample into a second branch flow channel after the main flow channel is filled with the driving liquid, stopping introducing the first sample and the second sample when the first sample and the second sample reach preset volumes, continuously introducing the driving liquid so that the first sample and the second sample are separated from the branch flow channels when flowing to a junction area of the branch flow channels and the main flow channel, and driving a liquid drop to be mixed, which is formed by the first sample and the second sample, to move to the electrode group by using the driving liquid;
s202, driving the liquid drop to be uniformly mixed to move towards an electrode group by using the driving liquid, and loading a first voltage signal of 30V to the first sub-electrode and the second sub-electrode in sequence when the orthographic projection of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the first sub-electrode so as to enable the liquid drop to be uniformly mixed to move along the main runner;
s203, when the liquid drop to be mixed is coincident with the center of the second sub-electrode, stopping introducing the driving liquid, adjusting to load a 0V voltage signal on the first sub-electrode, and loading a 60V voltage signal on the second sub-electrode, so that the dielectric layer generates reversible dielectric breakdown, the liquid drop to be mixed is electrolyzed to generate bubbles, and the preset time is kept, so that the first sample and the second sample in the liquid drop to be mixed are mixed uniformly;
and S204, after the preset duration of voltage loading on the electrode group, stopping voltage loading on the electrode group, continuously introducing the driving liquid, and driving the uniformly mixed liquid drops to flow out of the liquid outlet.
The microfluidic system provided in the embodiments of the present application includes the above microfluidic device provided in the embodiments of the present application.
In summary, according to the microfluidic device, the sample mixing method and the microfluidic system provided by the embodiment of the application, the dielectric layer and the electrode group are arranged on the upper substrate of the microfluidic device, and reversible dielectric breakdown can occur on the dielectric layer by applying voltage to the electrode group, so that bubbles can be generated by electrolyzing liquid drops of a sample to be mixed in a micro-channel, the sample can be quickly mixed by using the stirring effect of the bubbles, the sample mixing efficiency in the microfluidic device is improved, and the detection efficiency of the microfluidic device is improved. In addition, the microfluidic device provided by the embodiment of the application combines a micro-channel type droplet movement driving mode by using the driving liquid with a digital microfluidic droplet driving mode, so that the microfluidic device has the advantages of high control efficiency of the channel type microfluidic device, large droplet control flux and high control precision of the digital microfluidic device.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present application without departing from the spirit and scope of the application. Thus, if such modifications and variations of the present application fall within the scope of the claims of the present application and their equivalents, the present application is intended to include such modifications and variations as well.

Claims (19)

1. A microfluidic device, characterized in that it comprises: a lower substrate and an upper substrate provided to the cartridge;
the lower substrate includes: the lower substrate base plate is positioned on a micro-channel which is positioned on one side of the lower substrate base plate facing the upper substrate and used for containing liquid drops;
the upper substrate includes: the upper substrate comprises an upper substrate base plate, a plurality of electrode groups and a dielectric layer, wherein the electrode groups are positioned on one side, facing the lower substrate, of the upper substrate base plate;
the orthographic projection of the electrode group falls into the orthographic projection of the micro-channel;
the set of electrodes is configured to: and applying a voltage to the electrode group to enable reversible dielectric breakdown of the dielectric layer.
2. The microfluidic device according to claim 1, wherein the micro flow channel comprises: the device comprises a main runner extending along a first direction and a plurality of pairs of branch runners intersected with the main runner;
each pair of branch flow passages includes: the first branch flow channel and the second branch flow channel are respectively positioned on two sides of the main flow channel;
the orthographic projection of the electrode group falls into the orthographic projection of the main flow passage.
3. The microfluidic device according to claim 2, wherein each of the electrode sets comprises two first sub-electrodes arranged along a first direction, and one second sub-electrode positioned between the two first sub-electrodes; the first direction is a direction in which the main flow passage extends.
4. Microfluidic device according to claim 3, wherein the width of the second sub-electrode is greater than the width of the first sub-electrode in the first direction.
5. The microfluidic device according to claim 3, wherein in a first direction, a width of the first sub-electrode and a width of the second sub-electrode are both smaller than a diameter of the droplet; and in the first direction, when the orthographic projection of the center of the liquid drop is superposed with the orthographic projection of the center of the second sub-electrode, the orthographic projection of the liquid drop and the orthographic projections of the two first sub-electrodes are overlapped.
6. The microfluidic device according to claim 2, wherein the upper substrate further comprises: the first liquid inlet hole, the plurality of second liquid inlet holes, the plurality of third liquid inlet holes and the liquid outlet hole penetrate through the upper substrate;
on the lower substrate base plate, the orthographic projection of the first liquid inlet hole is overlapped with the orthographic projection of the main flow channel in the starting point region of the main flow channel, the liquid outlet hole is overlapped with the orthographic projection of the main flow channel in the terminal region of the main flow channel, and the orthographic projection of the second liquid inlet hole is overlapped with the orthographic projection of the first branch flow channel in the starting point region of the first branch flow channel; and the orthographic projection of the third liquid inlet hole is overlapped with the orthographic projection of the second branch flow channel in the starting point area of the second branch flow channel.
7. The microfluidic device according to claim 6, wherein the number of the electrode sets is equal to the number of pairs of the branch channels, and each of the electrode sets is located on a side of a pair of the branch channels away from the first inlet hole.
8. The microfluidic device according to claim 2, wherein the lower substrate further comprises: the first electrode layer is positioned on one side, facing the upper substrate, of the lower substrate and positioned in the micro flow channel; the first electrode layer is at least located in the main runner.
9. The microfluidic device according to claim 8, further comprising a ground electrode electrically connected to the first electrode layer; the microfluidic device further comprises: and the driving chip is electrically connected with the electrode group.
10. The microfluidic device according to any of claims 1 to 9, further comprising: the first optical assembly and the second optical assembly are respectively positioned on two sides of the micro-channel in the plane direction perpendicular to the micro-fluidic device;
the first optical assembly includes: a first optical filter;
the second optical assembly includes: the second optical filter is arranged on the micro-lens array on any side of the second optical filter, and the collimation and planarization layer is arranged on the light inlet side of the micro-lens array;
the orthographic projection of the first optical component and the orthographic projection of the second optical component at least cover the micro-channel.
11. The microfluidic device of claim 10, wherein the second optical assembly further comprises: an anti-reflective layer between the microlens array and the collimating planarizing layer.
12. The microfluidic device according to claim 10, wherein the lower substrate further comprises: the first electrode layer is positioned on one side, facing the upper substrate, of the lower substrate and is positioned in the micro flow channel;
the first optical assembly is positioned between the lower substrate base plate and the first electrode layer; or the first optical assembly is positioned on one side of the first electrode layer, which is far away from the lower substrate; or the first optical assembly is positioned on one side of the lower substrate base plate, which is far away from the upper substrate base plate;
the second optical assembly is positioned on one side of the upper substrate base plate, which is far away from the lower substrate base plate; alternatively, the second optical assembly is located between the upper substrate base plate and the electrode set; or the second optical assembly is positioned on one side of the electrode group, which is far away from the lower substrate, and the upper substrate is positioned between the second optical filter and the micro-lens array.
13. The microfluidic device according to claim 10, wherein the first optical assembly is located between the upper substrate base plate and the set of electrodes; or the first optical assembly is positioned on one side of the upper substrate base plate, which is far away from the lower substrate base plate;
the second optical assembly is positioned on one side of the lower substrate base plate, which is far away from the upper substrate base plate; or the second optical assembly is positioned on one side of the lower substrate base plate facing the upper substrate base plate; or the lower substrate base plate is positioned between the micro-lens array and the second optical filter.
14. A sample mixing method using the microfluidic device according to any one of claims 1 to 13, wherein the method comprises:
in the first stage, a driving liquid, a first sample and a second sample to be mixed are introduced into the micro-channel, and the driving liquid is used for driving the droplets to be mixed, which are composed of the first sample and the second sample, to move towards the electrode group;
in the second stage, when the orthographic projection of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the electrode group, voltage is loaded on the electrode group, and the liquid drop to be uniformly mixed is driven to move;
and in the third stage, when the liquid drop to be uniformly mixed is coincident with the center of the electrode group, stopping introducing the driving liquid, adjusting the voltage loaded on the electrode group to enable the dielectric layer to generate reversible dielectric breakdown, and enabling the liquid drop to be uniformly mixed to be electrolyzed to generate bubbles so as to uniformly mix the first sample and the second sample in the liquid drop to be uniformly mixed.
15. The method of claim 14, wherein the micro fluidic channel comprises: the device comprises a main runner extending along a first direction and a plurality of pairs of branch runners intersected with the main runner; and (2) introducing a driving liquid, a first sample to be uniformly mixed and a second sample into the micro flow channel, wherein the method specifically comprises the following steps:
and continuously introducing a driving liquid into the main runner, introducing a first sample into the first branch runner and introducing a second sample into the second branch runner after the main runner is filled with the driving liquid, and continuously introducing the driving liquid so as to separate the first sample and the second sample from the branch runners when the first sample and the second sample flow to the intersection region of the branch runners and the main runner.
16. The method of claim 14, wherein the micro fluidic channel comprises: the device comprises a main runner extending along a first direction and a plurality of pairs of branch runners intersected with the main runner; each electrode group comprises two first sub-electrodes arranged along a first direction and a second sub-electrode positioned between the two first sub-electrodes; when the orthographic projection of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the electrode group, applying voltage to the electrode group, and the method specifically comprises the following steps:
before the orthographic projection of the center of the liquid drop to be uniformly mixed is overlapped with the orthographic projection of the center of the second sub-electrode, loading a first voltage signal to the first sub-electrode and the second sub-electrode in sequence so as to enable the liquid drop to be uniformly mixed to move along the main runner.
17. The method according to claim 16, wherein the lower substrate comprises a first electrode layer, the first electrode layer is electrically connected with a ground potential, and when the droplet to be mixed coincides with the center of the electrode group, the voltage applied to the electrode group is adjusted, specifically comprising:
and applying a second voltage signal to the first sub-electrode to enable the potential difference between the second sub-electrode and the first sub-electrode to be not less than the dielectric layer reversible dielectric breakdown critical voltage, wherein the potential of the first sub-electrode relative to the first electrode layer is 0, and applying a third voltage signal to the second sub-electrode to enable the potential difference between the second sub-electrode and the first sub-electrode to be not less than the dielectric layer reversible dielectric breakdown critical voltage.
18. The method of claim 15, wherein after the third stage, the method further comprises:
and in the fourth stage, after the preset duration of voltage loading on the electrode group is finished, the voltage application on the electrode group is stopped, the driving liquid is continuously introduced, and the uniformly mixed liquid drops are driven to flow out from the liquid outlet.
19. A microfluidic system comprising a microfluidic device according to any one of claims 1 to 13.
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