CN107855142A - A kind of detection chip and detection device based on microflow control technique - Google Patents

A kind of detection chip and detection device based on microflow control technique Download PDF

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Publication number
CN107855142A
CN107855142A CN201711059630.6A CN201711059630A CN107855142A CN 107855142 A CN107855142 A CN 107855142A CN 201711059630 A CN201711059630 A CN 201711059630A CN 107855142 A CN107855142 A CN 107855142A
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detection chip
control technique
electrochemical luminescence
capping layer
microflow control
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CN107855142B (en
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范晶
黄卫人
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Shenzhen Second Peoples Hospital
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Shenzhen Second Peoples Hospital
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76Chemiluminescence; Bioluminescence
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure

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  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Plasma & Fusion (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

The present invention relates to micro fluidic chip technical field, a kind of electrochemical luminescence detection chip and detection device based on microflow control technique are provided, detection chip includes basalis, loaded layer and capping layer, multiple electrodes unit is provided with basalis, loaded layer is provided with multiple through holes, multiple through holes correspond to form multiple reaction tanks with multiple electrodes unit, capping layer bottom is provided with multiple grooves, multiple grooves correspond the top cover that reaction tank is formed at the top of each reaction tank, ostium is additionally provided with capping layer, tap hole, connected between multiple grooves by fluid channel, the both ends of fluid channel connect with ostium and tap hole respectively.Detection chip includes multiple reaction tanks in the present invention, can carry out multiple biochemical or chemical index detections simultaneously to sample;Only have tap hole, ostium when in use to be in communication with the outside, most of reaction is completed in the micro sprue system of closing, effectively reduces external environment condition to reaction and the interference of detection process.

Description

A kind of detection chip and detection device based on microflow control technique
Technical field
The present invention relates to micro fluidic chip technical field, especially provides a kind of electrochemical luminescence inspection based on microflow control technique Survey chip.
Background technology
Electrochemical luminescence (Electrochemiluminescence, ECL) is that chemiluminescence is combined with electrochemistry, is passed through Apply certain voltage to be electrochemically reacted, the raw materials of some electricity produced in electrode surface, then these electric biomass it Between or electric biomass and system in excitation state is formed by electron transmission between some components, returned to ground state by excitation state and produced A kind of raw luminescence phenomenon.
Electrochemical luminescence have the advantages that high sensitivity, reaction system are stable, analyze speed it is fast be widely used to biology, The field such as medical science, pharmacy, clinic, environment, food, immune and nucleic acid hybridization analysis and Industrial Analysis.But electrochemical luminescence Exist more operating procedure, system complex, easily by environmental disturbances, the shortcomings of electrode requirement is high, Reusability easy cross pollution.
The content of the invention
It is an object of the invention to provide a kind of electrochemical luminescence detection chip and detection device based on microflow control technique, Aim to solve the problem that when being detected in the prior art with Electrochemiluminescence technology more operating procedure, system complex, easily by environment Interference, electrode require the technical problems such as height, the easy cross pollution of Reusability.
To achieve the above object, the technical solution adopted by the present invention is:A kind of electrochemical luminescence based on microflow control technique Detection chip, including basalis, loaded layer and the capping layer for being sequentially stacked and being bonded from the bottom to top, set on the basalis Have a multiple electrodes unit, the loaded layer is provided with the through hole of loaded layer described in multiple up/down perforations, multiple through holes with it is more The individual electrode unit corresponds to form multiple reaction tanks, and the capping layer bottom is provided with multiple grooves, multiple grooves The top cover that reaction tank is formed at the top of each reaction tank is corresponded, envelope described in up/down perforation is additionally provided with the capping layer Ostium, the tap hole of cap rock, connected by fluid channel between multiple grooves, the both ends of the fluid channel respectively with it is described Ostium and tap hole connection.
Further, multiple electrode units, which are laid on the basalis, forms electrode zone, the electrode zone The area of plane be more than the loaded layer the area of plane and the capping layer the area of plane.
Further, the quantity of the electrode unit is even number, and electrode unit described in even number uniformly lines up two row, two Arrange the electrode unit to be symmetrical arranged, each electrode unit parallel interval is set in each column, and multiple through holes are uniformly lined up Two row, the two row through holes are symmetrical arranged, and multiple grooves uniformly line up two row, and the two row grooves are symmetrical arranged.
Further, the fluid channel includes the sprue placed in the middle between the two row grooves and by the main flow The branch flow passage that road extends to each groove, the ostium are located at one end of the sprue, and the tap hole is located at institute State the other end of sprue.
Further, the basalis includes substrate, and the electrode unit is on the substrate using silk-screen printing Electrode pattern uses vapour deposition, the electrode pattern being sputtered on the substrate.
Further, the material of the substrate is polyvinyl chloride, makrolon, dimethyl silicone polymer or silicon chip.
Further, the loaded layer and the capping layer are polymethyl methacrylate or polydimethyl siloxane material It is process using etching, casting or injection molding.
Further, biomolecule or chemical reactant are loaded with the electrode unit.
Further, the through hole circular in cross-section, the groove cross section are rounded.
A kind of detection device, it has the above-mentioned electrochemical luminescence detection chip based on microflow control technique.
Beneficial effects of the present invention:The electrochemical luminescence detection chip based on microflow control technique of the present invention includes multiple anti- Ying Chi, multiple biochemical or chemical index detections can be carried out simultaneously to sample;The chip only has tap hole, ostium when in use It is in communication with the outside, most of course of reaction is completed in the relatively micro sprue system of closing, effectively reduces external environment condition to reaction With the interference of detection process;And said chip is simple in construction, it is easily integrated and realizes automation with reference to supporting automation equipment Detection.
Brief description of the drawings
Technical scheme in order to illustrate the embodiments of the present invention more clearly, below will be to embodiment or description of the prior art In the required accompanying drawing used be briefly described, it should be apparent that, drawings in the following description be only the present invention some Embodiment, for those of ordinary skill in the art, without having to pay creative labor, can also be according to these Accompanying drawing obtains other accompanying drawings.
Fig. 1 is the structural representation of the electrochemical luminescence detection chip provided in an embodiment of the present invention based on microflow control technique Figure;
Fig. 2 is the structural representation of basalis in the embodiment of the present invention;
Fig. 3 is the floor map of basalis in the embodiment of the present invention;
Fig. 4 is the structural representation of loaded layer in the embodiment of the present invention;
Fig. 5 is the structural representation after capping layer inversion in the embodiment of the present invention;
Fig. 6 is the structure of micro sprue system in chips of the embodiment of the present invention (omitting basalis, loaded layer and capping layer) Schematic diagram;
Wherein, each reference in figure:
100-basalis, 110-electrode unit, 120-substrate, 130-working electrode, 140-to electrode, 150-electricity Polar region domain, 200-loaded layer, 210-through hole, 300-capping layer, 310-groove, 320-ostium, 330-tap hole, 340-fluid channel, 341-sprue, 342-branch flow passage, 400-reaction tank.
Embodiment
Embodiments of the invention are described below in detail, the example of the embodiment is shown in the drawings, wherein from beginning to end Same or similar label represents same or similar element or the element with same or like function.Below with reference to attached The embodiment of figure description is exemplary, it is intended to for explaining the present invention, and is not considered as limiting the invention.
In the description of the invention, it is to be understood that term " length ", " width ", " on ", " under ", "front", "rear", The orientation or position relationship of the instruction such as "left", "right", " vertical ", " level ", " top ", " bottom " " interior ", " outer " is based on accompanying drawing institutes The orientation or position relationship shown, it is for only for ease of the description present invention and simplifies description, rather than instruction or the dress for implying meaning Put or element there must be specific orientation, with specific azimuth configuration and operation, therefore it is not intended that to limit of the invention System.
In addition, term " first ", " second " are only used for describing purpose, and it is not intended that instruction or hint relative importance Or the implicit quantity for indicating indicated technical characteristic.Thus, define " first ", the feature of " second " can be expressed or Implicitly include one or more this feature.In the description of the invention, " multiple " are meant that two or more, Unless otherwise specifically defined.
In the present invention, unless otherwise clearly defined and limited, term " installation ", " connected ", " connection ", " fixation " etc. Term should be interpreted broadly, for example, it may be fixedly connected or be detachably connected, or integrally;Can be that machinery connects Connect or electrically connect;Can be joined directly together, can also be indirectly connected by intermediary, can be in two elements The connection in portion or the interaction relationship of two elements.For the ordinary skill in the art, can be according to specific feelings Condition understands the concrete meaning of above-mentioned term in the present invention.
Referring to figs. 1 to Fig. 6, the electrochemical luminescence detection chip provided in an embodiment of the present invention based on microflow control technique includes Basalis 100, loaded layer 200 and capping layer 300.Basalis 100, loaded layer 200 and capping layer 300 are from the bottom to top successively It is stacked and is bonded.Multiple electrodes unit 110 is provided with basalis 100, loaded layer 200 is provided with multiple up/down perforations loading The through hole 210 of layer 200, multiple through holes 210 correspond with multiple electrodes unit 110 and form multiple reaction tanks 400, due to loading Layer 200 has certain thickness, therefore the through hole 210 for penetrating the loaded layer 200 has certain height, and the side wall of through hole 210 is then The side wall of reaction tank 400 is formed, the electrode unit 110 of basalis 100 then forms the bottom of reaction tank 400, the bottom of capping layer 300 Provided with multiple grooves 310, each groove 310 Open Side Down top and non-through capping layer 300 top, multiple grooves 310 are one by one The corresponding top cover that reaction tank 400 is formed positioned at each top of reaction tank 400, the up/down perforation capping layer is additionally provided with capping layer 300 300 ostium 320 and tap hole 330, connected by fluid channel 340 between multiple grooves 310, the both ends point of fluid channel 340 Do not connected with ostium 320 and tap hole 330.
The above-mentioned electrochemical luminescence detection chip based on microflow control technique provided in an embodiment of the present invention includes multiple reactions Pond 400, multiple biochemical or chemical index detections can be carried out simultaneously to sample;The chip only has tap hole 330, stream when in use Enter hole 320 to be in communication with the outside, most of course of reaction is completed in the relatively micro sprue system of closing, effectively reduces external environment condition To reaction and the interference of detection process;And said chip is simple in construction, it is easily integrated and is realized with reference to supporting automation equipment Automatic detection.
Reference picture 2, Fig. 3, in the embodiment of the present invention, basalis 100 includes substrate 120 and the electrode located at substrate 120 Unit 110.Substrate 120 can be thin polymer film or polymer sheet or silicon chip.Specifically, thin polymer film is that polyvinyl chloride is thin Film, polycarbonate film or polydimethylsiloxanefilm film.Polymer sheet can be polyvinyl chloride panel, polycarbonate plate or poly- Dimethyl siloxane plate.And electrode unit 110 is that graphene ink is printed on substrate 120 and through heat using screen printing technique The electrode pattern or use vapour deposition, the electrode pattern being sputtered on substrate 120 that processing is formed, can be with one on substrate 120 Secondary more than ten electrode units 110 of processing and fabricating.In the present embodiment, the electrode on substrate 120 includes working electrode 130 and to electricity Pole 140, the two is mutually not attached to, and cooperates, and is laid in 12 similar electrode units 110 of formation on substrate 120.So, when After basalis 100, loaded layer 200 are bonded with capping layer 300,12 reaction tanks 400 are formed on chip, a liquid can be detected simultaneously 12 biochemistry or chemical index of body sample, sample dosage only need hundreds of microlitres.It is of course also possible to form it on substrate 120 The electrode unit 110 of his quantity, correspondingly, set respectively on loaded layer 200 and capping layer 300 corresponding to through hole 210 and recessed Groove 310.
In the present embodiment, 12 electrode units 110 are laid in formation 150,12 electrode units of electrode zone on substrate 120 110 uniformly line up two row, and two row electrode units 110 are symmetrical arranged, and each parallel interval of electrode unit 110 is set in each column.Substrate 120 area of plane is about 76*26mm2, and the area of plane of electrode zone 150 is about 63.5*26mm2.Electrode zone 150 is not The plane of substrate 120 is taken completely, but the area of plane of electrode zone 150 is more than loaded layer 200 it can be seen from Fig. 1, Fig. 2 The area of plane and capping layer 300 the area of plane.So, when basalis 100, loaded layer 200 are bonded with capping layer 300 Afterwards, electrode zone 150 some be exposed to outside chip, so, be easy to set the exposed electrode zone 150 with external instrument Standby circuit system electrical connection.
In the present embodiment, the detection of detection chip is electricity consumption chemiluminescence mode, is carried out on electrode unit 110 different Modification, so as to obtain the function of being tested and analyzed in different field, such as can by nucleic acid, antibody, antigen biomolecule or its He is modified on electrode unit 110 chemical reactant, so as to obtain nucleic acid hybridization analysis, immuno-sandwich method or industrial detection analysis Function.
Reference picture 4, loaded layer 200 are polymethyl methacrylate or polydimethyl siloxane material using etching, casting Or injection molding is process.On loaded layer 200, through hole 210 also has 12, with 12 electrodes on basalis 100 Unit 110 corresponds, and so, 12 through holes 210 uniformly line up two row, and two row through holes 210 are symmetrical arranged.Loaded layer 200 Size is about 51*26*3mm3, its area of plane is less than the electrode zone 150 on basalis 100.In the present embodiment, through hole 210 Circular in cross-section, diameter is about 4mm.
Reference picture 5, the length and width size of capping layer 300 and the length and width comparable dimensions of loaded layer 200, but capping layer 300 Thickness is about 2mm.Also loaded layer 200 is identical for the material of capping layer 300, also with polymethyl methacrylate or poly dimethyl Silicone compositions are process using etching, casting or injection molding.The corresponding groove 310 of capping layer 300 is also 12, 12 grooves 310 uniformly line up two row, and two row grooves 310 are symmetrical arranged.Each cross section of groove 310 is also circle, its diameter It is identical with the diameter of through hole 210 on loaded layer 200, about 4mm.The depth of groove 310 is about 1mm, and the depth of fluid channel 340 is also 1mm.Fluid channel 340 includes the placed in the middle sprue 341 being located between two row grooves 310 and from sprue 341 to each groove 310 The branch flow passage 342 of extension, ostium 320 are located at one end of sprue 341, and tap hole 330 is another located at sprue 341 End.Ostium 320 and tap hole 330 be through hole 210, and reaction sample, reaction solution and cleaning solution are in core during for detecting Outflow and inflow on piece.
As shown in fig. 6, after basalis 100, loaded layer 200 are bonded with capping layer 300,12 by electrode unit 110, logical Reaction tank 400, fluid channel 340 and the ostium 320 of hole 210 and the formation of groove 310, the one connection of tap hole 330 form miniflow Road system, micro sprue system pass through ostium 320, tap hole 330 and ft connection.
To sum up, the electrochemical luminescence detection chip compact based on microflow control technique in the present embodiment, so its have Prestige develops into real-time test (point-of-care testing, POCT) equipment, and greatly reduces sample and reaction reagent Dosage, it is cost-effective;The chip includes 12 electrode units 110 and reaction tank simultaneously, can carry out multiple lifes simultaneously to sample Change or the detection of chemical index;The chip can use as the disposable products of instant throwing, effectively avoid Conventional electrochemical from sending out The problem of light technical equipment easy cross pollution;Simultaneously the chip using when only have tap hole 330, ostium 320 is in communication with the outside, Most of course of reaction is completed in the relatively micro sprue system of closing, effectively reduces external environment condition to reaction and detection process Interference;And Electrochemiluminescince has higher sensitivity and preferable reliability, the invention of the chip is expected to obtain relatively low Test limit;Simultaneously by carrying out different modifications to electrode unit 110, nucleic acid hybridization analysis, immuno-sandwich method or work can be obtained The function of industry detection and analysis.
The embodiment of the present invention additionally provides a kind of detection device (not shown), and it has above-mentioned based on micro-fluidic skill The electrochemical luminescence detection chip of art, because the chip structure is simple, it is easily integrated and automates, set so as to also improve detection Standby integrated level and automaticity.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention All any modification, equivalent and improvement made within refreshing and principle etc., should be included in the scope of the protection.

Claims (10)

  1. A kind of 1. electrochemical luminescence detection chip based on microflow control technique, it is characterised in that:Including being sequentially stacked from the bottom to top And basalis, loaded layer and the capping layer being bonded, multiple electrodes unit is provided with the basalis, is set on the loaded layer Have a through hole of loaded layer described in multiple up/down perforations, multiple through holes corresponded with multiple electrode units to be formed it is multiple Reaction tank, the capping layer bottom are provided with multiple grooves, and multiple grooves correspond the shape at the top of each reaction tank Into the top cover of reaction tank, ostium, the tap hole of capping layer described in up/down perforation are additionally provided with the capping layer, it is multiple described recessed Connected between groove by fluid channel, the both ends of the fluid channel connect with the ostium and the tap hole respectively.
  2. 2. the electrochemical luminescence detection chip according to claim 1 based on microflow control technique, it is characterised in that:Multiple institutes State electrode unit and be laid on the basalis and form electrode zone, the area of plane of the electrode zone is more than the loaded layer The area of plane and the capping layer the area of plane.
  3. 3. the electrochemical luminescence detection chip according to claim 1 based on microflow control technique, it is characterised in that:The electricity The quantity of pole unit is even number, and electrode unit described in even number uniformly lines up two row, and the two row electrode units are symmetrical arranged, Each electrode unit parallel interval is set in each column, and multiple through holes uniformly line up two row, and the two row through holes are symmetrically set Put, multiple grooves uniformly line up two row, and the two row grooves are symmetrical arranged.
  4. 4. the electrochemical luminescence detection chip according to claim 3 based on microflow control technique, it is characterised in that:It is described micro- Runner includes the sprue placed in the middle between the two row grooves and point from the sprue to each groove extension Branch flow passage, the ostium are located at one end of the sprue, and the tap hole is located at the other end of the sprue.
  5. 5. the electrochemical luminescence detection chip according to claim 1 based on microflow control technique, it is characterised in that:The base Bottom includes substrate, the electrode unit be using silk-screen printing in the electrode pattern on the substrate or using vapour deposition, The electrode pattern being sputtered on the substrate.
  6. 6. the electrochemical luminescence detection chip according to claim 5 based on microflow control technique, it is characterised in that:The base The material of plate is polyvinyl chloride, makrolon, dimethyl silicone polymer or silicon chip.
  7. 7. the electrochemical luminescence detection chip according to claim 1 based on microflow control technique, it is characterised in that:The dress Carrier layer is that polymethyl methacrylate or polydimethyl siloxane material use etching, casting or injection molding with the capping layer Mode is process.
  8. 8. the electrochemical luminescence detection chip according to claim 1 based on microflow control technique, it is characterised in that:The electricity Biomolecule or chemical reactant are loaded with pole unit.
  9. 9. the electrochemical luminescence detection chip according to any one of claim 1 to 8 based on microflow control technique, its feature It is:The through hole circular in cross-section, the groove cross section are rounded.
  10. A kind of 10. detection device, it is characterised in that:It has is based on micro-fluidic skill as claimed in any one of claims 1-9 wherein The electrochemical luminescence detection chip of art.
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CN108704684A (en) * 2018-09-04 2018-10-26 重庆科技学院 A kind of application method of detection multi-layer micro-fluidic chips
CN108745429A (en) * 2018-06-12 2018-11-06 南京岚煜生物科技有限公司 A kind of multichannel quickly detects microfluid detection chip
CN109374690A (en) * 2018-09-13 2019-02-22 中国科学院上海硅酸盐研究所 A kind of wireless microfluidic sensor
CN109929735A (en) * 2019-04-25 2019-06-25 湖南工业大学 A kind of plunger type detection of nucleic acids integration cartridge and its detection method
CN110004044A (en) * 2019-04-25 2019-07-12 湖南工业大学 A kind of Molecular Detection integration device and its detection method based on electrochemical sensing
CN110412021A (en) * 2019-08-06 2019-11-05 华南师范大学 A kind of electrochemical luminescence micro-fluidic chip of shared bipolar electrode cathode and its application
CN110735186A (en) * 2018-07-18 2020-01-31 李俊豪 Method for manufacturing biomedical chip
WO2020177774A1 (en) * 2019-03-01 2020-09-10 南京岚煜生物科技有限公司 Multi-channel microfluidic blood coagulation measurement chip
CN111659477A (en) * 2020-06-11 2020-09-15 厦门先明生物技术有限公司 Independent sample introduction micro-fluidic immunoassay joint inspection device
CN111822063A (en) * 2019-04-18 2020-10-27 京东方科技集团股份有限公司 Microfluidic chip, manufacturing method thereof and microfluidic device
CN112191284A (en) * 2020-06-18 2021-01-08 天津大学 Laboratory analysis platform on microfluidic ultrasonic electrochemical chip
CN113009143A (en) * 2020-06-17 2021-06-22 山东大学 Double-layer micro-fluidic chip for antibody detection and preparation method thereof

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