CN109182092A - A kind of micro-fluidic chip and its application for detection of nucleic acids - Google Patents
A kind of micro-fluidic chip and its application for detection of nucleic acids Download PDFInfo
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- 238000001514 detection method Methods 0.000 title claims abstract description 90
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 37
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 37
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 37
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000000758 substrate Substances 0.000 claims abstract description 25
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- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000008157 edible vegetable oil Substances 0.000 claims description 2
- ZHPNWZCWUUJAJC-UHFFFAOYSA-N fluorosilicon Chemical compound [Si]F ZHPNWZCWUUJAJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
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- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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Abstract
The present invention provides a kind of micro-fluidic chip for detection of nucleic acids, the present invention also provides a kind of preparation methods of above-mentioned micro-fluidic chip for detection of nucleic acids, and the present invention also provides a kind of methods that the above-mentioned micro-fluidic chip for detection of nucleic acids carries out microlayer model formula PCR reaction.A kind of micro-fluidic chip for detection of nucleic acids, chip substrates layer and chip channel layer including pressing encapsulation, the chip substrates layer is flat panel substrates, drop formation unit and detection unit are equipped in the chip channel layer, the drop formation unit includes oily phase sample inlet, aqueous sample entrance, oily phase sample inlet, aqueous sample pipeline and drop transport pipeline, and the detection unit includes that drop storage detection zone, drop insulated column, oil strain channel and oil mutually export.The present invention is integrated with drop formation unit and detection unit on the same chip, simplifies the structure of existing digital pcr chip.
Description
Technical field
The present invention relates to a kind of micro-fluidic chip, in particular to a kind of micro-fluidic chip for detection of nucleic acids and its answer
With belonging to biomedicine technical field.
Background technique
20 end of the centurys, Vogelstein etc. propose the concept of digital pcr (digitalPCR, dPCR), by by one
A sample is divided into tens to tens of thousands of parts, is assigned to different reaction members, each unit contains at least one the target point of copy
Sub (DNA template) carries out PCR amplification to target molecule respectively in each reaction member, to each anti-after amplification
The fluorescence signal of unit is answered to carry out statistical analysis.Digital pcr technology continues to develop, Bio-Rad, LIFE Technologies
And the producers such as RainDance release one after another the more mature digital pcr product of technology.The droplet that QuantaLife company develops
Digital pcr technology.The product have also obtained 2011 year Frost & Sullivan North America new product Innovation Awards.2011 10
Month, Bio-Rad corporate buyout QuantaLife and ddPCR technology has launched QX100, QX200 droplet type digital pcr
System.Different from other digital pcr technologies, Bio-Rad carries out droplet processing to sample.According to gene expression department of the said firm
Sales manager Richard Kurtz is introduced, their unique advantage is can to generate very uniform, duplicate 1 nanoliter of drop.This
The benefit of sample is that each sample forms 20,000 drop, and other systems can only be divided into 760-3,000 part.Get more
It is more, then mean that analysis is more accurate.
Digital pcr is a kind of nucleic acid molecules absolute quantitation technology.There are three types of method, photometries for current nucleic acid molecules quantitative
It is quantified based on the absorbance of nucleic acid molecules；Real-time fluorescence quantitative PCR (Real Time PCR) is based on Ct value, and Ct value just refers to
It can detecte the corresponding recurring number of fluorescent value；Digital pcr is newest quantitative technique, is carried out based on single-molecule PCR method
The nucleic acid quantification of counting is a kind of method of absolute quantitation.It is main to use the micro-fluidic of the popular research field of present analysis chemistry
Or droplet method, the nucleic acid solution after Macrodilution is dispersed in the microreactor or droplet of chip, each reactor
Nucleic acid-templated number is less than or is equal to 1.In this way by having the reactor of a nucleic acid templates will after PCR cycle
Fluorescence signal is provided, the reactor of template is not just without fluorescence signal.According to the volume of relative scale and reactor, so that it may
Extrapolate the nucleic acid concentration of original solution.
In existing commercial digital pcr chip, mostly use greatly and drop generated by chip piece, be transferred in PCR pipe into
Row amplification, is then then transferred in another piece of detection chip and carries out fluorescence detection, i.e., entire reaction is by " generating drop → PCR to add
Thermal response → detection " three parts composition, operation is comparatively laborious, while in the transfer process of drop, and there are the breakups of drop, transfer
Not exclusively, situations such as aerosol cross contamination, exists, and reduces the accuracy and reliability of digital pcr.
So as can develop a kind of fully integrated PCR reaction chip, realize on same chip from being loaded to detection
Whole detection process, while operator is liberated, it reduces operation and requires, cooperating equipment completion, which is loaded onto out, reports one-touch behaviour
Make, it is meaningful to the development of digital pcr.
Summary of the invention
The purpose of the present invention is to provide a kind of micro-fluidic chips for detection of nucleic acids, for generating microlayer model formula PCR
Reaction, drop formation function and detection function are integrated on same chip, are realized reaction detection combination, are solved background above
The problem of being proposed in technology.
Another object of the present invention is to provide a kind of preparation methods of above-mentioned micro-fluidic chip for detection of nucleic acids.
Another object of the present invention is to provide a kind of above-mentioned micro-fluidic chips for detection of nucleic acids to carry out microlayer model formula
The method of PCR reaction.
The technical solution adopted by the present invention to solve the technical problems is:
A kind of micro-fluidic chip for detection of nucleic acids, chip substrates layer and chip channel layer including pressing encapsulation are described
Chip substrates layer is flat panel substrates, is equipped with drop formation unit and detection unit, the drop in the chip channel layer
Generation unit includes oily phase sample inlet, aqueous sample entrance, oily phase sample inlet, aqueous sample pipeline and drop transporting tube
Road, oily phase sample inlet are set to oily phase sample inlet beginning, and aqueous sample entrance is set to aqueous sample pipeline beginning, oily phase sample
Line end and aqueous sample line end are crossed to form drop formation area, and drop formation area passes through the connection inspection of drop transport pipeline
Survey unit；The detection unit includes that drop storage detection zone, drop insulated column, oil strain channel and oil mutually export, drop
Insulated column is distributed in drop storage detection zone, and oil strain channel is set to the edge that oil mutually exports, and oil strain channel is Fence structure, is enclosed
Column spacing is less than liquid-drop diameter, and oil strain channel separation drop stores detection zone and mutually exports with oil, oily mutually outlet and drop transporting tube
Road is oppositely arranged.Oily phase sample is the organic solvent containing surfactant；Aqueous sample is to be mixed with amplification template, primer, glimmering
The PCR reaction system of light probe, dNTP and enzyme.
Preferably, the drop formation unit includes two oily phase sample inlets and an aqueous sample pipeline, two
A oil phase sample inlet is symmetrically arranged in an aqueous sample pipeline two sides, two oily phase sample inlet ends, a water phase samples
Product line end and drop transport pipeline beginning are crossed to form criss-cross construction.
Preferably, the oily phase sample inlet and aqueous sample pipeline are equipped with snakelike pipeline knot before line end
Structure.
Preferably, the detection unit further includes oily phase collecting region, oily phase collecting region is set to oil strain channel and detection
Between unit side, the end connection oil of oily phase collecting region is mutually exported.
Preferably, the detection unit is rectangular configuration, mutually outlet is located at rectangle to drop transport pipeline with oil
Two diagonal, and oil strain channel is set to the two sides that oil mutually exports, and drop insulated column is arranged in parallel with oil strain channel.
Preferably, the detection unit includes multiple drop insulated columns, multiple drop insulated columns are in the form of a column array junctions
Structure.
Preferably, the material of the chip substrates layer and chip channel layer be dimethyl silicone polymer, PMMA plastics,
COC plastics, PC plastic, glass or silicon.
A kind of preparation method of the micro-fluidic chip for detection of nucleic acids, method includes the following steps:
1, using graphic design software detail of design, photo etched mask is processed as with printer；
2, the structure of photo etched mask is transferred in chip substrates by lithographic methods, forms the drop formation of chip channel layer
Unit, and be filled the pipeline in drop formation unit with gel；
3, by the detection unit of machine tooling chip channel layer, gel is washed off out of drop formation unit after processing is completed,
Form complete chip channel layer；
4, one is formed by said chip channel layer and as the flat panel substrates encapsulation of chip substrates layer by pressing packaging method
Whole micro-fluidic chip.
A kind of method that the above-mentioned micro-fluidic chip for detection of nucleic acids carries out microlayer model formula PCR reaction, this method include
Following steps:
1, the organic solvent containing surfactant is added from oily phase sample inlet, the mass percentage of surfactant is 1%
~50%；Amplification template, the PCR reaction system of primer, fluorescence probe, dNTP and enzyme are had been mixed with from the addition of aqueous sample entrance；
Oily phase sample sandwiches aqueous sample under external power supply promotion, generates microlayer model in drop formation area；Microlayer model enters drop
Detection zone is stored, is closely arranged by drop insulated column, extra oily phase sample leads to filtered oil passage from oily mutually outlet discharge, directly
Microlayer model is generated completely to all oily phase samples and aqueous sample；
2, PCR amplification is carried out by heating；
3, the light field and fluorescence field signal that drop stores detection zone are recorded by microscope；Respectively to the light field of record and fluorescence field
Signal is analyzed, and microlayer model quantity and whole microlayer model quantity of the metering with fluorescence, proportionally calculating is detected
Nucleic acid concentration.
Preferably, organic solvent is selected from one or more of mineral oil, fluorosilicon oil or edible oil, in organic solvent
Surfactant is selected from one or more of neopelex, polysorbas20 or polyvinylpyrrolidone.
Preferably, the content of surfactant is 5% ~ 10% in organic solvent.
The beneficial effects of the present invention are:
1, the present invention is integrated with drop formation unit and detection unit on the same chip, simplifies existing digital pcr chip
Structure；
2, the present invention is provided with drop insulated column and oil strain channel near drop storage detection zone, keeps microlayer model more effective
The tiling for concentrating on drop storage detection zone and close rule, facilitate subsequent reaction and detection, and guarantee testing result
Stability；
3, micro-fluidic chip of the invention can do PCR heating reaction to drop storage detection zone simultaneously and detect, and simplify
The reaction process of digital pcr；
4, the invention avoids the losses that common detection methods may cause sample, generate all samples all micro-
Drop guarantees the integrality of test result, reduces the possibility of missing inspection, and realize the quantitative analysis to sample.
Detailed description of the invention
Fig. 1 is schematic perspective view of the invention；
Fig. 2 is schematic view of the front view of the invention；
Fig. 3 is the structural schematic diagram of drop formation unit of the present invention；
Fig. 4 is the structural schematic diagram of detection unit of the present invention；
Fig. 5 is the structural schematic diagram in oil strain channel of the present invention.
In figure: 1, chip substrates layer, 2, chip channel layer, 3, drop formation unit, 4, detection unit, 5, oily phase sample enters
Mouthful, 6, aqueous sample entrance, 7, oily phase sample inlet, 8, aqueous sample pipeline, 9, drop transport pipeline, 10, snakelike pipeline knot
Structure, 11, drop formation area, 12, drop storage detection zone, 13, drop insulated column, 14, oil strain channel, 15, oil mutually outlet, 16,
Oily phase collecting region.
Specific embodiment
Below by specific embodiment, and in conjunction with attached drawing, technical scheme of the present invention will be further explained in detail.It answers
Work as understanding, implementation of the invention is not limited by the following examples, the accommodation in any form done to the present invention and/or
Change falls within the scope of the present invention.
Embodiment:
A kind of micro-fluidic chip for detection of nucleic acids as depicted in figs. 1 and 2,1 He of chip substrates layer including pressing encapsulation
Chip channel layer 2, chip substrates layer are flat panel substrates, and the material of chip substrates layer and chip channel layer is PMMA plastics.Core
Drop formation unit 3 and detection unit 4 are equipped in piece channel layer, chip channel layer is to add chip substrates by micro-processing method
Work keeps its surface band fluted and pipe passage, and for the depth in channel according to the diameter design of required drop, range can be from 0.5 μm
~ 5mm, optimized scope are 10 μm ~ 200 μm.
As shown in figure 3, drop formation unit includes oily phase sample inlet 5, aqueous sample entrance 6, two oily phase sample cells
7, one, road aqueous sample pipeline 8 and drop transport pipeline 9, oily phase sample inlet are set to oily phase sample inlet beginning, water phase sample
Product entrance is set to aqueous sample pipeline beginning, and oily phase sample inlet and aqueous sample entrance are respectively used to inject oily phase sample and water
Phase sample, oily phase sample are the organic solvents containing surfactant, and aqueous sample is to be mixed with amplification template, primer, fluorescence to visit
The PCR reaction system of needle, dNTP and enzyme.
Oily phase sample inlet and aqueous sample pipeline are equipped with snakelike pipeline structure 10 before line end.Two oily phase samples
Quality control road is symmetrically arranged in an aqueous sample pipeline two sides, two oily phase sample inlet ends, an aqueous sample pipeline end
End is crossed to form criss-cross construction, oily phase sample inlet end and aqueous sample line end phase with drop transport pipeline beginning
Friendship forms drop formation area 11, and drop formation area passes through drop transport pipeline connecting detection unit.
As shown in figure 4, detection unit includes drop storage detection zone 12, drop insulated column 13, oil strain channel 14 and oil
Mutually outlet 15.Detection unit is rectangular configuration, and mutually outlet is located at two, rectangle diagonally to drop transport pipeline with oil, and oil strain is logical
Road is set to the two sides that oil mutually exports, and drop insulated column is arranged in parallel with oil strain channel, and drop insulated column is equipped with multiple, multiple liquid
Drop insulated column is in the form of a column array structure and is distributed in drop storage detection zone.As shown in figure 5, oil strain channel is Fence structure, enclose
Column spacing is less than liquid-drop diameter, and oil strain channel separation drop stores detection zone and mutually exports with oil.Detection unit further includes oily mutually receipts
Collect area 16, oily phase collecting region is set between oil strain channel and detection unit side, and the end connection oil of oily phase collecting region mutually exports.
This for detection of nucleic acids micro-fluidic chip preparation method the following steps are included:
1, using graphic design software detail of design, photo etched mask is processed as with printer；
2, the structure of photo etched mask is transferred in chip substrates by lithographic methods, forms the drop formation of chip channel layer
Unit, and be filled the pipeline in drop formation unit with gel；
3, by the detection unit of machine tooling chip channel layer, gel is washed off out of drop formation unit after processing is completed,
Form complete chip channel layer；
4, one is formed by said chip channel layer and as the flat panel substrates encapsulation of chip substrates layer by pressing packaging method
Whole micro-fluidic chip.
The processing difficulties of micro-fluidic chip for detection of nucleic acids are, the size of drop formation unit and detection unit
Differ greatly, wherein the pipeline size of drop formation unit in the micron-scale (can be processed for from 10 microns to 1000 micron), usually
It can only be manufactured using the method for photoengraving；And detection unit is to guarantee that amount of droplets, size are larger, in tens centimetres of ranks,
It is excessively high using the cost of photoengraving, usually processed with injection molding or lathe；The bound fraction of the two needs to be maintained at same
In plane, difficulty of processing is very big.It, then will with gel using first photoengraving drop formation unit in order to overcome the problems, such as this
The pipe passage filling of drop formation unit protects, then carries out machine tooling, finally washes off gel from pipe passage,
To realize the structure processing of two kinds of different scales, while small scale structures will not be damaged while processing coarse scale structures
Wound.
This for detection of nucleic acids micro-fluidic chip carry out microlayer model formula PCR reaction method the following steps are included:
1, the organic solvent containing surfactant is added from oily phase sample inlet, the mass percentage of surfactant exists
8%, organic solvent is mineral oil, and the surfactant in organic solvent is polyvinylpyrrolidone；It is added from aqueous sample entrance
Have been mixed with amplification template, the PCR reaction system of primer, fluorescence probe, dNTP and enzyme；Oily phase sample is pushed in external power supply
Under from both sides sandwich aqueous sample, generate microlayer model in drop formation area, the external power supply way of propelling pressure injection that can be positive is penetrated
The modes such as pump injection or negative pressure absorbing；Microlayer model enters drop storage detection zone, is closely arranged by drop insulated column, extra
Oily phase sample leads to filtered oil passage from oily mutually outlet discharge, until all oily phase samples and aqueous sample generate microlayer model completely；
2, PCR amplification is carried out by heating；Heating method can be infrared heating, microwave heating, Ohmic contact heating, hot plate
The modes such as heating, Hot-blast Heating；
3, the light field and fluorescence field signal that drop stores detection zone are recorded by microscope；Respectively to the light field of record and fluorescence field
Signal is analyzed, and microlayer model quantity and whole microlayer model quantity of the metering with fluorescence, proportionally calculating is detected
Nucleic acid concentration.
The conventional die of microlayer model PCR reaction is carried out, what drop formation position and detection position were separate from, in liquid
Drop is taken out drop with pipettor after generating from the collection device of generation area, is added dropwise in detection zone, while it is single for requiring drop
Layer is spread out, and cannot be overlapped, just be can be carried out digital measuring in this way.This method has loss to sample, and the drop of generation cannot be complete
Portion is detected, and has missing inspection may.Simultaneously when injecting detection zone, due to being mixed with a large amount of drop formation oil in drop, cause
Drop also has an impact to the interpretation of result in irregular dispersion in detection zone.When being drawn simultaneously with pipettor, due to injection
Be drop and oil mixture, it cannot be guaranteed that the amount of sample is all fixed every time, so the qualitative analysis of result can only be carried out.And
The method of progress microlayer model formula PCR reaction of the invention avoids the loss that common detection methods may cause sample, makes institute
Some samples can all generate microlayer model, guarantee the integrality of test result, reduce the possibility of missing inspection, and realize to sample
Quantitative analysis.
Above-mentioned embodiment is only a preferred solution of the present invention, not the present invention is made in any form
Limitation, there are also other variations and modifications on the premise of not exceeding the technical scheme recorded in the claims.
Claims (10)
1. a kind of micro-fluidic chip for detection of nucleic acids, it is characterised in that: the micro-fluidic chip for being used for detection of nucleic acids includes
The chip substrates layer and chip channel layer of encapsulation are pressed, the chip substrates layer is flat panel substrates, the chip channel layer
It is interior to be equipped with drop formation unit and detection unit, the drop formation unit include oily phase sample inlet, aqueous sample entrance,
Oily phase sample inlet, aqueous sample pipeline and drop transport pipeline, oily phase sample inlet are set to oily phase sample inlet beginning, water phase
Sample inlet is set to aqueous sample pipeline beginning, and it is raw that oily phase sample inlet end and aqueous sample line end are crossed to form drop
At area, drop formation area passes through drop transport pipeline connecting detection unit；The detection unit include drop storage detection zone,
Drop insulated column, oil strain channel and oil mutually export, and drop insulated column is distributed in drop storage detection zone, and oil strain channel is set to
The edge of oily mutually outlet, oil strain channel are Fence structure, and fence spacing is less than liquid-drop diameter, the storage inspection of oil strain channel separation drop
It surveys area and is mutually exported with oil, mutually outlet is oppositely arranged oil with drop transport pipeline.
2. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the drop is raw
It include two oily phase sample inlets and an aqueous sample pipeline at unit, two oily phase sample inlets are symmetrically arranged in a water
Phase sample inlet two sides, two oily phase sample inlet ends, an aqueous sample line end and drop transport pipeline beginning phase
Friendship forms criss-cross construction.
3. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the oily phase sample
Quality control road and aqueous sample pipeline are equipped with snakelike pipeline structure before line end.
4. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the detection list
Member further includes oily phase collecting region, and oily phase collecting region is set between oil strain channel and detection unit side, the end of oily phase collecting region
Connection oil mutually exports.
5. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the detection list
Member is rectangular configuration, and mutually outlet is located at two, rectangle diagonally to drop transport pipeline with oil, and oil strain channel is set to oil and mutually exports
Two sides, drop insulated column is arranged in parallel with oil strain channel.
6. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the detection list
Member includes multiple drop insulated columns, and multiple drop insulated columns are in the form of a column array structure.
7. a kind of micro-fluidic chip for detection of nucleic acids according to claim 1, it is characterised in that: the chip base
The material of material layer and chip channel layer is dimethyl silicone polymer, PMMA plastics, COC plastics, PC plastic, glass or silicon.
8. a kind of preparation method of such as described in any item micro-fluidic chips for detection of nucleic acids of claim 1-7, feature
It is: method includes the following steps:
(1), using graphic design software detail of design, photo etched mask is processed as with printer；
(2), the structure of photo etched mask is transferred in chip substrates by lithographic methods, the drop for forming chip channel layer is raw
The pipeline in drop formation unit is filled at unit, and with gel；
(3), by the detection unit of machine tooling chip channel layer, after processing is completed by gel from drop formation unit wash-in
Fall, forms complete chip channel layer；
(4), one is formed by said chip channel layer and as the flat panel substrates encapsulation of chip substrates layer by pressing packaging method
A whole micro-fluidic chip.
9. a kind of as the described in any item micro-fluidic chips progress microlayer model formula PCR for detection of nucleic acids of claim 1-7 are anti-
The method answered, it is characterised in that: method includes the following steps:
(1), the organic solvent containing surfactant is added from oily phase sample inlet, the mass percentage of surfactant exists
1%~50%；From aqueous sample entrance be added have been mixed with amplification template, primer, fluorescence probe, dNTP and enzyme PCR reactant
System；Oily phase sample sandwiches aqueous sample under external power supply promotion, generates microlayer model in drop formation area；Microlayer model enters liquid
Drop stores detection zone, is closely arranged by drop insulated column, and extra oily phase sample leads to filtered oil passage and is discharged from oily mutually outlet,
Until thering is oily phase sample and aqueous sample to generate microlayer model completely more；
(2), PCR amplification is carried out by heating；
(3), the light field and fluorescence field signal that drop stores detection zone are recorded by microscope；Respectively to the light field of record and fluorescence
Field signal is analyzed, and microlayer model quantity and whole microlayer model quantity of the metering with fluorescence are proportionally calculated and is detected
Nucleic acid concentration.
10. the method that the micro-fluidic chip according to claim 9 for detection of nucleic acids carries out microlayer model formula PCR reaction,
It is characterized by: the organic solvent is selected from one or more of mineral oil, fluorosilicon oil or edible oil, in organic solvent
Surfactant is selected from one or more of neopelex, polysorbas20 or polyvinylpyrrolidone.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811224801.0A CN109182092A (en) | 2018-10-19 | 2018-10-19 | A kind of micro-fluidic chip and its application for detection of nucleic acids |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811224801.0A CN109182092A (en) | 2018-10-19 | 2018-10-19 | A kind of micro-fluidic chip and its application for detection of nucleic acids |
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| CN109182092A true CN109182092A (en) | 2019-01-11 |
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| CN109797096A (en) * | 2019-01-25 | 2019-05-24 | 中国科学院苏州生物医学工程技术研究所 | Digital pcr chip and preparation method thereof, preparation facilities, application method |
| CN109825426A (en) * | 2019-02-21 | 2019-05-31 | 中国科学院苏州生物医学工程技术研究所 | Integral type drop microfluidic chip structure and preparation method, micro-fluidic chip component |
| CN110305941A (en) * | 2019-06-21 | 2019-10-08 | 苏州锐讯生物科技有限公司 | A method of single sample hereditary information is obtained based on microflow control technique |
| CN112280663A (en) * | 2020-10-29 | 2021-01-29 | 王晓冬 | Droplet single-layer tiled nucleic acid detection chip packaging part and chip packaging method |
| CN113042121A (en) * | 2021-03-26 | 2021-06-29 | 中国科学院上海微系统与信息技术研究所 | Integrated chip for exosome nucleic acid detection, detection method and application |
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| CN113969232A (en) * | 2021-11-12 | 2022-01-25 | 南通大学 | Digital micro-fluidic chip device for nucleic acid detection and use method |
| CN113980796A (en) * | 2021-10-25 | 2022-01-28 | 苏州缔因安生物科技有限公司 | Micro-droplet bearing chip, application thereof, nucleic acid detection module and method |
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| CN110305941A (en) * | 2019-06-21 | 2019-10-08 | 苏州锐讯生物科技有限公司 | A method of single sample hereditary information is obtained based on microflow control technique |
| CN114829627A (en) * | 2020-05-18 | 2022-07-29 | 深圳华大生命科学研究院 | Method for enriching nucleic acid and constructing sequencing library based on digital microfluidic platform |
| CN114829627B (en) * | 2020-05-18 | 2024-04-30 | 深圳华大生命科学研究院 | Method for enriching nucleic acid and constructing sequencing library based on digital microfluidic platform |
| WO2021232186A1 (en) * | 2020-05-18 | 2021-11-25 | 深圳华大生命科学研究院 | Digital micro-fluidic platform-based nucleic acid enrichment and sequencing library construction methods |
| CN112280663A (en) * | 2020-10-29 | 2021-01-29 | 王晓冬 | Droplet single-layer tiled nucleic acid detection chip packaging part and chip packaging method |
| CN113042121A (en) * | 2021-03-26 | 2021-06-29 | 中国科学院上海微系统与信息技术研究所 | Integrated chip for exosome nucleic acid detection, detection method and application |
| CN113789259A (en) * | 2021-09-09 | 2021-12-14 | 哈尔滨工业大学 | Machine learning-assisted microdroplet digital nucleic acid detection device and detection method |
| CN113980796A (en) * | 2021-10-25 | 2022-01-28 | 苏州缔因安生物科技有限公司 | Micro-droplet bearing chip, application thereof, nucleic acid detection module and method |
| CN113980796B (en) * | 2021-10-25 | 2023-12-26 | 苏州缔因安生物科技有限公司 | Micro-droplet bearing chip, application thereof, nucleic acid detection module and method |
| CN113969232A (en) * | 2021-11-12 | 2022-01-25 | 南通大学 | Digital micro-fluidic chip device for nucleic acid detection and use method |
| CN115807061A (en) * | 2022-08-19 | 2023-03-17 | 国科温州研究院(温州生物材料与工程研究所) | Real-time digital LAMP nucleic acid detection method based on micro-droplets |
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