CN207722815U - Microlayer model generates chip - Google Patents
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- CN207722815U CN207722815U CN201721458103.8U CN201721458103U CN207722815U CN 207722815 U CN207722815 U CN 207722815U CN 201721458103 U CN201721458103 U CN 201721458103U CN 207722815 U CN207722815 U CN 207722815U
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Abstract
The utility model provides a kind of microlayer model generation chip, and it includes a centre bore, transhipment of the centre bore for microlayer model generation chip during injection injection molding material in microlayer model generation chip fabrication process and mass production that the microlayer model, which generates chip,；One or more microlayer model generation units are arranged in the centre bore both sides centered on centre bore, and each microlayer model generation unit has independently produced microlayer model.The CD preparation process of the microlayer model chip combination industrial quarters maturation, uniform micron dimension " Water-In-Oil " or " oil-in-water " microlayer model can quickly and reliably be generated, microlayer model chip uses thermoplastic material, material and batch machining are of low cost, traditional round annular compact disk structure is modified, utilizes the space of CD to greatest extent.
Description
Technical field
The utility model is related to microlayer model digital pcr technical fields, and in particular to a kind of microlayer model generation chip.
Background technology
Microlayer model digital pcr technology (droplet digital PCR, ddPCR) is a kind of nucleic acid based on single-molecule PCR
Absolute quantification analysis technology.Highly sensitive, high accuracy advantage is just next as industry with it for microlayer model digital pcr technology
Revolutionary technology.In recent years, with micro-nano manufacturing technology and micro-fluidic technologies (micro-nanofabrication and
Microfluidics development), microlayer model digital pcr technology encounter the best opportunity of break-through skill bottleneck.The technology by
Micro-fluidic chip generates a diameter of a few micrometers drops for arriving hundreds of microns；Microlayer model wraps up unimolecule or unicellular, reaches reaction
It is totally-enclosed with detecting, it is fully integrated.Microlayer model digital pcr System Working Principle is：Generating instrument by special microlayer model first will
Sample to be tested is assigned in " Water-In-Oil " microlayer model of a large amount of nanoliter levels (a diameter of a few micrometers to hundreds of microns), the number of microlayer model
Amount is in million ranks.It is mutually isolated by oil reservoir between microlayer model since microlayer model quantity is enough, therefore each microlayer model is suitable
The DNA unimolecules of sample to be tested are contained only in one " microreactor ", microlayer model；Then, distinguish for these microlayer models
Pcr amplification reaction is carried out, and the fluorescence signal of drop is detected one by one by microlayer model analyzer, there is the micro- of fluorescence signal
It is 1 to drip interpretation, and the not droplet interpretation of fluorescence signal is 0.Finally, according to Poisson distribution principle and the number of positive droplet with than
Example can obtain the target dna molecule number of sample to be tested, realize the absolute quantitation to sample of nucleic acid.
One typical " Water-In-Oil " microlayer model generating process is：" oil phase " sample is under extraneous gas pressure, from level
Direction flows into micron level pipeline；" water phase " sample flows into micron level pipeline under extraneous gas pressure, from vertical direction.Two
The immiscible liquid of kind crosses at " cross " microfluidic structures.Due to the liquid surface of " oil phase " sample and " water phase " sample
Shearing force caused by force difference and impressed pressure, " water phase " sample are divided by " oil phase " sample from continuous phase at cross structure
Discrete microlayer model.Microlayer model is the form of " Water-In-Oil ", and outside is " oil phase " sample.
One core devices of microlayer model round pcr are that microlayer model generates chip.It is micro- in order to meet the needs of clinical examination
Drop formation chip needs to have following characteristics：(1) micron dimension " Water-In-Oil "/" water quickly, reliable, parallel generation is uniform
Packet oil " microlayer model, the material and processing cost of the micro-fluid chip of (2) based on microflow control technique are low.
Currently, the micro-fluidic chip based on dimethyl silicone polymer (PDMS) has been widely used for generating microlayer model.Research
Personnel have the PDMS microlayer model chips of micron dimension using the processing of soft light carving technology.First, researcher uses thick photoresist
(such as：SU-8 thickness glue) and conventional lithographic techniques process the mold with micron accuracy, high-aspect-ratio on silicon-based substrate surface.
Then, by PDMS precursors and its cast of crosslinking agent mixed solution in this die surface.It is handled by elevated cure, mold separation,
Prepare the elastic PDMS micro-fluidic structures chip of complementary structure.The PDMS micro-fluidic structures chip passes through a step with glass substrate
Reversible keying step, the micro-fluidic chip for ultimately forming encapsulation are used for drop formation.
After PDMS microlayer model chips are successfully prepared, outlet is generated using mechanical processing work in its sample inlet, microlayer model
Skill is punched, assembly sample feeding pipe, out sample tube." oil phase " sample, " water phase " sample are drawn by manual mode in syringe.So
Afterwards, " oil phase " sample, " water phase " sample are injected by sample feeding pipe in PDMS microlayer model chips by external injection pump.Finally,
The microlayer model of generation is collected by out sample tube in routine experiment consumptive material, such as EP pipes.Although PDMS microlayer model chip materials
R＆D costs are low, laboratory processing technology is simple, but its existing deficiency includes：
(1) PDMS is thermoelastic polymer material, such material is not suitable for technical grade injection molding, packaging technology.Add by hand
The PDMS microlayer model chip reliabilities of work are poor.
(2) PDMS microlayer models chip batch processing cost is high.
For the deficiency of PDMS microlayer model chip preparing process, researcher is based on using hot moulding, Shooting Technique preparation
The micro-fluidic chip of thermoplastic material.But these chip preparing process Distance Batch metaplasias Cheng Shang has distance, with high costs, limit
Extensive use of the microlayer model chip in clinical examination field is made.
Utility model content
The step of generating chip for existing microlayer model, the utility model proposes one micro- liquid based on polymer material
Drop generates chip.The CD preparation process of the microlayer model chip combination industrial quarters maturation, its main feature is that：(1) it quickly and reliably gives birth to
At uniform micron dimension " Water-In-Oil " or " oil-in-water " microlayer model, (2) microlayer model chip uses thermoplastic material, such as poly- carbonic acid
Ester (PC), cyclic olefine copolymer (COP), polymethyl methacrylate (PMMA), polypropylene (PP), material and batch machining cost
Cheap, (3) are modified traditional round annular compact disk structure, utilize the space of CD, the life of arranged in parallel microlayer model to greatest extent
At runner.
A kind of microlayer model generation chip is provided in the present invention, and it includes a center that the microlayer model, which generates chip,
Hole, the centre bore is for micro- during injection injection molding material in microlayer model generation chip fabrication process and mass production
The transhipment of drop formation chip；One or more microlayer model generation units are arranged in the centre bore both sides centered on centre bore,
Each microlayer model generation unit has independently produced microlayer model.
In one embodiment, the microlayer model generation unit includes an oil phase sample inlet, an aqueous sample
Entrance, oil phase sample inlet, aqueous sample pipeline, a microlayer model generation area and one generate microlayer model outlet.
In one embodiment, it includes that the microlayer model generation chip includes two to 20 that the microlayer model, which generates chip,
Four microlayer model generation units, preferably six to 16 microlayer model generation units.
In one embodiment, four microlayer model generation units of each equidistant arrangement in the centre bore both sides；Eight micro-
Distance is equal between the adjacent oil phase sample inlet of drop formation unit, adjacent aqueous sample of eight microlayer model generation units
The equal distance between the adjacent generation microlayer model outlet of eight microlayer model generation units of distance is equal between entrance.
In one embodiment, each distance be equal to eight channel sample loading gun suction pipette head of standard between away from
From.
In one embodiment, the oil phase sample inlet and/or the aqueous sample pipeline are far from the center
The arc pipe structure in hole.
In one embodiment, the microlayer model generation unit includes two oil phase sample inlets and an aqueous sample
Pipeline generates " Water-In-Oil " microlayer model；Or the microlayer model generation unit includes an oil phase sample inlet and two water phases
Sample inlet generates " oil-in-water " microlayer model.
In one embodiment, hollow flow resistance area, oil phase sample are provided in the pipeline after the oil phase sample inlet
After product flow through hollow flow resistance area, it is divided into two-way and respectively enters oil phase sample inlet, generate " Water-In-Oil " microlayer model；Or institute
It states and is provided with hollow flow resistance area in the pipeline after aqueous sample entrance and is divided into after aqueous sample flows through hollow flow resistance area
Two-way respectively enters aqueous sample pipeline, generates " oil-in-water " microlayer model.
In one embodiment, the oil phase sample inlet is provided with oil phase sample filtering area and/or the water phase sample
Aqueous sample filtering area is provided in quality control road.
In one embodiment, oil phase sample filtering area and/or the aqueous sample filtering area are one group respectively
Columnar arrays structure.
In one embodiment, the microlayer model generation unit further includes in the microlayer model generation area and the generation
Microlayer model between microlayer model outlet generates observation area.
In one embodiment, it further includes at least one location hole that the microlayer model, which generates chip,.
In one embodiment, it is preferably ten that the microlayer model generation chip, which is round or polygon, the polygon,
Hexagon, octagon or quadrangle.
In one embodiment, the microlayer model generates chip and uses thermoplastic material, preferably makrolon, cycloolefin
Copolymer, polymethyl methacrylate and polypropylene.
Description of the drawings
It in order to more clearly explain the technical solutions in the embodiments of the present application, below will be to needed in the embodiment
Attached drawing is briefly described, it should be apparent that, the accompanying drawings in the following description is only some embodiments described in the application, right
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings
Its attached drawing.
Fig. 1 is that the utility model microlayer model generates chip structure schematic diagram；
Fig. 2 is the hollow flow resistance plot structure figure that the utility model microlayer model generates the injection of chip oil phase sample；
Fig. 3 is the filtering section configuration schematic diagram that the utility model microlayer model generates the injection of chip oil phase sample；
Fig. 4 is the filtering section configuration schematic diagram that the utility model microlayer model generates the injection of chip aqueous sample；
Fig. 5 is that the utility model microlayer model generates chip cross generating structure schematic diagram；With
Fig. 6 is that the utility model microlayer model generates chip observation plot structure schematic diagram.
Specific implementation mode
In order to make art technology field personnel more fully understand the technical solution in the application, below in conjunction with following knot
Closing embodiment, the utility model is described in further detail, it is clear that and described embodiments are only a part of embodiments of the present application,
Instead of all the embodiments.Based on the embodiment in the application, those of ordinary skill in the art are not making creative labor
The all other embodiment obtained under the premise of dynamic, shall fall within the protection scope of the present application.Below in conjunction with the accompanying drawings and implement
Example is further described the utility model.
One, microlayer model generates chip overall structure
As shown in Figure 1 chip structure schematic diagram is generated for microlayer model.From left to right, it is designed on an octagonal chip
8 microlayer model generation units 1, in the chips the heart have a centre bore 2, which comes from CD processing technology, for noting
Enter the transhipment of substrate during injection molding material and mass production.Typical round compact disk structure is not easy to position, and is by chip manufacture
Eight-sided formation, and two location holes 3 are processed, it is convenient for the location fit of microlayer model chip and relevant device.In centre bore two
Side respectively equidistantly arrange 4 identical microlayer model generation units 1, be used for parallel generation microlayer model.
As shown in Figure 1, each drop formation unit 1 includes from top to bottom：Oil phase sample inlet 111, hollow flow resistance area
112,121, two oil phase sample inlets, 113, two oil phase filtering areas 114, aqueous sample entrance aqueous sample filtering areas
122, an aqueous sample pipeline 123, microlayer model generation area 13, microlayer model generate observation area 14 and generate microlayer model outlet 15.
Microlayer model as shown in Figure 1 generates chip and is corrected to the normal structure of general disc, can utilize CD to greatest extent
Space, arranged in parallel microlayer model generate runner.Meanwhile the chip processed using precise injection molding technique, in conjunction with hollow flow resistance area and
Filtering area designs, and quickly, reliably generates uniform micron dimension " Water-In-Oil " microlayer model.
Two, oil phase sample pipetting volume structure
As shown in Figures 2 and 3, first with external air pump or peristaltic pump, oil phase sample is injected into oil phase sample and enters
Mouth 111.In order to accurately control oil phase sample injection volume, back-shaped flow resistance area 112 is devised after oil phase sample inlet 111, it should
Back-shaped flow resistance area 112 is made of multiple U-tube roads.Oil phase sample can be infiltrated in surface of polymer material, not apply pressure
Under the conditions of, by capillarity, oil phase sample automatically flows into microchannel.Under extreme case, oil phase sample under capillary action,
Constant flow.The purpose for designing back-shaped flow resistance area 112 is to accurately control oil phase sample injection volume, reduces oil phase sample to the greatest extent in hair
Constant flow under spy's use in microchannel so that oil phase sample injection volume is only controlled by external air pump or peristaltic pump.
Later, oil phase sample passes through an oil phase split entry, is divided into two two oil phase samples into same design
Quality control road 113, the oil phase sample inlet 113 are the arcuate structure pipeline far from centre bore 2.As shown in figure 5, two oil phase samples
Respectively enter an oil phase filtering area 114 in pipeline 113.Oil phase filtering area 114 is one group of columnar arrays structure.As shown in figure 4,
Columnar arrays structure has multiple rows of columnar arrays staggered.Impurity present in oil phase (particle, silk wadding fiber etc.) is blocked in
At this group of column structure, the generation of microlayer model is not influenced.
Three, aqueous sample is loaded structure
As shown in figure 4, first with external air pump or peristaltic pump, aqueous sample is injected into aqueous sample entrance 121.
It is designed similar to oil phase sample feeding, aqueous sample enters an aqueous sample filtering area 122 and an aqueous sample pipeline
123.Filtering area is one group of columnar arrays structure, it is therefore an objective to filter the impurity in aqueous sample, eliminate impurity for drop formation
Influence.
Four, microlayer model generates plot structure
As shown in figure 5, two oil phase sample inlets 113 and an aqueous sample pipeline 123 are in 13 shape of microlayer model generation area
At " cross " structure, it to be used for the generation of microlayer model.Two-way " oil phase " sample is by two oil phase sample inlets 113 in extraneous gas
Under pressure effect, micron level pipeline is flowed into from horizontal direction；" water phase " sample passes through aqueous sample pipeline 123 in extraneous gas all the way
Under pressure effect, micron level pipeline is flowed into from vertical direction.Two kinds of immiscible liquid cross at " cross " microfluidic structures.
Shearing force caused by surface tension of liquid difference and impressed pressure due to " oil phase " sample and " water phase " sample, " water phase " sample
Discrete microlayer model is divided into from continuous phase by " oil phase " sample at cross structure.
Five, observation area and microlayer model collection opening structure
As shown in fig. 6, microlayer model generates 14 purpose of observation area it is easy for that optical system is coordinated to monitor microlayer model in real time.Micro- liquid
The feature structure that drop generates observation area 14 is to design closed micro-structure on the microchannel left side.Due in the enclosed construction not
Oil phase/water phase liquid, microlayer model are flowed through, stable still image is collected convenient for Systems for optical inspection, it is flat to focus on microchannel
Face, to obtain clearly testing result.The microlayer model of generation is by generating 15 outflow of microlayer model outlet.
Six, chip positioning structure-centre bore, octagon borderline structure, location hole
It is modified for the normal structure of general disc, utilizes the space of CD to greatest extent, and existed convenient for chip
Positioning during use.Centre bore 2 comes from CD processing technology, for injecting during injection molding material and mass production
The transhipment of substrate.Typical round compact disk structure is not easy to position.Therefore, it is eight-sided formation by chip manufacture, and processes two
Location hole 3 is convenient for the location fit of microlayer model chip and relevant device.
It should be understood that the utility model disclosed is not limited only to specific method, scheme and the substance of description, because
These are alterable.It will also be understood that purpose of the terminology used here just for the sake of the specific embodiment scheme of description, and
It is not intended to limit the scope of the utility model, the scope of the utility model is limited solely by the attached claims.
Those skilled in the art, which will also be appreciated that or be able to confirm that, uses no more than routine experiment, institute herein
Many equivalents of the specific embodiment of the utility model stated.These equivalents are also contained in the attached claims
In.
Claims (17)
1. a kind of microlayer model generates chip, it is characterised in that：It includes a centre bore, the center that the microlayer model, which generates chip,
Hole generates core for microlayer model during injection injection molding material in microlayer model generation chip fabrication process and mass production
The transhipment of piece；One or more microlayer model generation units, each microlayer model is arranged in the centre bore both sides centered on centre bore
Generation unit has independently produced microlayer model.
2. microlayer model according to claim 1 generates chip, it is characterised in that：The microlayer model generation unit includes one
Oil phase sample inlet, an aqueous sample entrance, oil phase sample inlet, aqueous sample pipeline, a microlayer model generation area and one
A generation microlayer model outlet.
3. microlayer model according to claim 2 generates chip, it is characterised in that：The microlayer model generate chip include two to
24 microlayer model generation units.
4. microlayer model according to claim 3 generates chip, it is characterised in that：The microlayer model generate chip include six to
16 microlayer model generation units.
5. microlayer model according to claim 3 generates chip, it is characterised in that：Each equidistant arrangement in centre bore both sides
Four microlayer model generation units；Between the adjacent oil phase sample inlet of eight microlayer model generation units distance it is equal, eight it is micro-
Distance is equal between the adjacent aqueous sample entrance of drop formation unit and the micro- liquid of adjacent generation of eight microlayer model generation units
Distance is equal between oozing mouth.
6. microlayer model according to claim 5 generates chip, it is characterised in that：Each distance is equal to eight channel of standard
The distance between sample loading gun suction pipette head.
7. microlayer model according to claim 2 generates chip, it is characterised in that：The oil phase sample inlet and/or described
Aqueous sample pipeline is the arc pipe structure far from the centre bore.
8. microlayer model according to claim 2 generates chip, it is characterised in that：The microlayer model generation unit includes two
Oil phase sample inlet and an aqueous sample pipeline generate " Water-In-Oil " microlayer model；Or the microlayer model generation unit includes
One oil phase sample inlet and two aqueous sample pipelines generate " oil-in-water " microlayer model.
9. microlayer model according to claim 2 generates chip, it is characterised in that：Pipeline after the oil phase sample inlet
In be provided with hollow flow resistance area, after oil phase sample flows through hollow flow resistance area, be divided into two-way and respectively enter oil phase sample inlet,
Generate " Water-In-Oil " microlayer model；Or hollow flow resistance area, aqueous sample are provided in the pipeline after the aqueous sample entrance
After flowing through hollow flow resistance area, it is divided into two-way and respectively enters aqueous sample pipeline, generate " oil-in-water " microlayer model.
10. microlayer model according to claim 2 generates chip, it is characterised in that：The oil phase sample inlet is provided with oil
It is provided with aqueous sample filtering area in phase sample filtering area and/or the aqueous sample pipeline.
11. microlayer model according to claim 10 generates chip, it is characterised in that：Oil phase sample filtering area and/or
The aqueous sample filtering area is one group of columnar arrays structure respectively.
12. microlayer model according to claim 2 generates chip, it is characterised in that：The microlayer model generation unit further includes
In the microlayer model generation area and the microlayer model generation observation area generated between microlayer model outlet.
13. generating chip according to any microlayer models of claim 1-12, it is characterised in that：The microlayer model generates chip
It further include at least one location hole.
14. generating chip according to any microlayer models of claim 1-12, it is characterised in that：The microlayer model generates chip
It is round or polygon.
15. microlayer model according to claim 14 generates chip, it is characterised in that：The polygon is ten hexagons, eight
Side shape or quadrangle.
16. generating chip according to any microlayer models of claim 1-12, it is characterised in that：The microlayer model generates chip
Using thermoplastic material.
17. microlayer model according to claim 16 generates chip, it is characterised in that：The thermoplastic material be makrolon,
Cyclic olefine copolymer, polymethyl methacrylate or polypropylene.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201721458103.8U CN207722815U (en) | 2017-11-06 | 2017-11-06 | Microlayer model generates chip |
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| CN201721458103.8U CN207722815U (en) | 2017-11-06 | 2017-11-06 | Microlayer model generates chip |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109746060A (en) * | 2017-11-06 | 2019-05-14 | 北京新羿生物科技有限公司 | Microlayer model generates chip |
| CN110193387A (en) * | 2018-10-16 | 2019-09-03 | 长春技特生物技术有限公司 | A kind of totally-enclosed micro-fluidic chip and lotion droplet preparation system |
| CN110813395A (en) * | 2019-11-29 | 2020-02-21 | 南通大学 | Suction head droplet generating device for rapidly preparing micro droplets |
| CN109746060B (en) * | 2017-11-06 | 2024-05-24 | 北京新羿生物科技有限公司 | Micro-droplet generation chip |
-
2017
- 2017-11-06 CN CN201721458103.8U patent/CN207722815U/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109746060A (en) * | 2017-11-06 | 2019-05-14 | 北京新羿生物科技有限公司 | Microlayer model generates chip |
| CN109746060B (en) * | 2017-11-06 | 2024-05-24 | 北京新羿生物科技有限公司 | Micro-droplet generation chip |
| CN110193387A (en) * | 2018-10-16 | 2019-09-03 | 长春技特生物技术有限公司 | A kind of totally-enclosed micro-fluidic chip and lotion droplet preparation system |
| CN110813395A (en) * | 2019-11-29 | 2020-02-21 | 南通大学 | Suction head droplet generating device for rapidly preparing micro droplets |
| CN110813395B (en) * | 2019-11-29 | 2022-02-08 | 南通大学 | Suction head droplet generating device for rapidly preparing micro droplets |
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Address after: Room 310, 44 Block No. 13, North Second Article, Zhongguancun, Haidian District, Beijing, 100190 Co-patentee after: Tsinghua University Patentee after: Beijing Xinyi Biotechnology Co., Ltd. Address before: Room 310, 44 Block No. 13, North Second Article, Zhongguancun, Haidian District, Beijing, 100190 Co-patentee before: Tsinghua University Patentee before: Beijing Tianjian Wellcome Biotechnology Co. Ltd. |
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