CN207981204U - Microlayer model generates system - Google Patents
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Abstract
The utility model provides a kind of microlayer model generation system, and the microlayer model generation system includes that the microlayer model generation system includes the first component and second component, and the first component is fixedly connected with second component；The first component is that microlayer model generates chip, is used for the generation of microlayer model；The second component is microlayer model sample pipetting volume and generates microlayer model collection device, is used for the collection of the microlayer model of the oil phase sample of the first component and the sample-adding and generation of aqueous sample；It includes a centre bore that the microlayer model, which generates chip,；It is provided with and the matched microlayer model sample-adding of each microlayer model generation unit and collector unit with the second component.The microlayer model of the utility model generates micron dimension " Water-In-Oil "/" oil-in-water " microlayer model that system can quickly, reliable, parallel generation is uniform, and material and batch machining are of low cost；Sample injection, drop collection process are convenient, and whole process is not likely to produce cross contamination.
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 system.
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.
The committed step of microlayer model digital pcr technology is micron dimension " Water-In-Oil " quick, reliable, that parallel generation is uniform
Microlayer model.A core technology for generating microlayer model is that the microlayer model of design and processing based on microflow control technique generates system.It is micro-
Drop formation system is widely used in clinical detection and needs to have following principle：(1) quickly, reliable, parallel generation is uniform
Micron dimension " Water-In-Oil "/" oil-in-water " microlayer model, the material and processing cost of the micro-fluid chip of (2) based on microflow control technique
Low, (3) simple operation, (4) drop formation does not generate cross contamination during collecting.
Currently, the micro-fluidic chip based on dimethyl silicone polymer (PDMS) has been widely used for generating microlayer model.First,
Researcher has the PDMS microlayer model chips of micron dimension using soft light carving technology (manual operation) processing.When PDMS microlayer models
It after chip is successfully prepared, generates outlet in its sample inlet, microlayer model and is punched using mechanical processing technique, assembly sample feeding pipe goes out
Sample pipe." oil phase " sample, " water phase " sample are drawn by manual mode in syringe.It then, will " oil by external injection pump
Phase " sample, " water phase " sample are by sample feeding pipe injection PDMS microlayer model chips.Finally, the microlayer model of generation passes through out sample tube
It is collected into routine experiment consumptive material, such as EP pipes.Although PDMS microlayer model chip material R＆D costs are low, laboratory processes work
Skill 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.
(3) injection of PDMS microlayer models chip sample, drop are collected as the cumbersome manual operation flow of process, are unsuitable for clinic
Examine application.
(4) cross contamination is easy tod produce during drop formation, collection.
For the deficiency of PDMS microlayer model chips, industrial quarters is for disadvantage mentioned above expansion research and development.The BioRad companies in the U.S.
The microlayer model based on polymer material, which has been developed, with RainDance Technologies companies generates system.Biorad companies
Microlayer model generate system, generation microlayer model needs be transferred in EP pipes from chip manually.The microlayer model of RainDance companies
Generation system, oil phase sample need external instrument sample-adding, and with high costs.These microlayer models generate existing for system itself not
Foot, limits its extensive use in clinical examination field.
Utility model content
The deficiency of system is generated for existing microlayer model, the utility model provides a kind of microlayer model based on polymer material
Generation system.The microlayer model generate system the characteristics of be：(1) micron dimension " Water-In-Oil " quickly, reliable, parallel generation is uniform
Or " oil-in-water " microlayer model, (2) microlayer model chip is using thermoplastic material (such as makrolon material (PC), cyclic olefine copolymer
(COP) or polymethyl methacrylate material (PMMA), polypropylene (PP)), material and batch machining are of low cost, (3) by
In external pressure source, System on Chip/SoC is generated using the microlayer model, sample injection, drop collection process become convenient, (4) integrated form
Microlayer model generates system design, and whole process is not likely to produce cross contamination.
In one embodiment, the utility model provides a kind of microlayer model generation system, and the microlayer model generates system
Including the first component and second component, the first component is fixedly connected with second component；The first component is that microlayer model generates core
Piece is used for the generation of microlayer model；The second component is microlayer model sample pipetting volume and generates microlayer model collection device, is used for first
The collection of the microlayer model of the oil phase sample of component and the sample-adding and generation of aqueous sample；The microlayer model generates chip
One centre bore, the centre bore generate injection injection molding material and mass production in chip fabrication process for the microlayer model
Microlayer model generates the transhipment of chip in journey；One or more microlayer models are arranged centered on centre bore and are generated for the centre bore both sides
Unit, each microlayer model generation unit have independently produced microlayer model；It is provided with and each microlayer model with the second component
The matched microlayer model sample-adding of generation unit and collector unit, the microlayer model sample-adding of each microlayer model generation unit corresponding thereto
Coordinate sample-adding, generation and the collection for carrying out microlayer model with collector unit.
In one embodiment, the first component and the second component pass through dispensing mode or ultrasonic welding mode
It is sealedly and fixedly connected.
In one embodiment, the first component and the second component are formed by integrated injection molding respectively.
In one embodiment, the first component and the second component are thermoplastic materials, preferably poly- carbonic acid
Ester material, cyclic olefine copolymer or polymethyl methacrylate, polypropylene.
In one embodiment, there are four first component settings, eight or 12 microlayer model generation units；With
The second component is provided with corresponding four, eight or 12 microlayer model generation units.
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, 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 micro-pipe roads and a water phase micro-pipe
Road or an oil phase micro-pipe road and two water phase micro-pipe roads；Oil phase micro-pipe road and water phase micro-pipe road form cross and hand over
Structure is pitched, microlayer model is used to form.
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, oil phase sample pipetting volume slot, oil phase sample-adding through-hole, water are provided with above the second component
Phase sample pipetting volume slot and water phase are loaded through-hole, wherein oil phase sample-adding through-hole and water phase sample-adding through-hole are separately positioned on institute
It states in oil phase sample pipetting volume slot and aqueous sample sample-adding trench bottom, the oil phase sample and the aqueous sample pass through respectively
They enter the first component；Second component lower section is provided with sample collection device.
In one embodiment, the volume of the oil phase sample pipetting volume slot and the aqueous sample loading slot is respectively 1
~900 microlitres, preferably 5~500 microlitres, more preferably 100~200 microlitres.
In one embodiment, the sample collection device is included in the generation microlayer model that its both ends is respectively set and receives
Mouth and microlayer model collection port, and the storage chamber that prestores；The microlayer model that the first component generates by the microlayer model receiving port into
Enter second component, then passes through the storage chamber that prestores, and be finally collected from the microlayer model collection port.
In one embodiment, the microlayer model collection port is set as the outlet with oblique side wall construction, at its end
It is provided with connecting rod, microlayer model is instilled through the connecting rod in microlayer model collection vessel.
In one embodiment, the microlayer model collection vessel is centrifuge tube, and the connecting rod has curved wall；Institute
It states connecting rod to go deep into inside the centrifuge tube, be collected convenient for microlayer model.
In one embodiment, it further includes third member that the microlayer model, which generates system, and the third member seals institute
The oil phase sample and aqueous sample of second component are stated, and external pressure is applied by it.
In one embodiment, it is also respectively provided with convenient for the two fixation on the first component and the second component
Connect the location hole positioned.
In one embodiment, it is arranged on the first component on microlayer model generation observation area and the second component and sets
Observation window is set, for coordinating optical system to monitor the microlayer model of generation in real time.
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 a kind of microlayer model of embodiment of the utility model generates system global structure schematic diagram；
Fig. 2 is a kind of first component structural schematic diagram of embodiment of the utility model；
Fig. 3 is a kind of hollow flow resistance plot structure figure of the oil phase sample injection of embodiment of the utility model；
Fig. 4 is a kind of filtering section configuration schematic diagram of the oil phase sample injection of embodiment of the utility model；
Fig. 5 is a kind of filtering section configuration schematic diagram of the aqueous sample injection of embodiment of the utility model；
Fig. 6 is a kind of cross generating structure schematic diagram of embodiment of the utility model；
Fig. 7 is a kind of change saltire generating structure schematic diagram of embodiment of the utility model；
Fig. 8 is a kind of observation area structural schematic diagram of embodiment of the utility model；
Fig. 9 is a kind of second component structural schematic diagram of embodiment of the utility model；With
Figure 10 is a kind of collection device structural schematic diagram of the second component of embodiment of the utility model.
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 models generate system structure
As shown in Figure 1, the microlayer model generation system of the utility model includes：The first component 1 and second component 2, first
Part 1 is that microlayer model generates chip, and second component 2 is microlayer model sample pipetting volume and generation droplet collection device.The first component 1 and
Two components 2 are fixedly connected.
In some embodiments, it further includes third member 3 that the microlayer model of the utility model, which generates system, and third member is
Microlayer model oil phase sample pipetting volume slot for sealing second component 2 and aqueous sample loading slot.Such as watertight sealing of third member 3
Pad, such as is prepared with silica gel, the watertight potting pad can on can be provided with stomata, for applying pressure by its, act on
It is the crimping air-tightness ensured between external pressure source and second component, and convenient for applying external pressure.It is pressed by means of outside
Power, two kinds of samples are flowed into the first component from second component, into the fluid channel of the first component.Finally, the microlayer model of generation
It is collected into microlayer model collection vessel, such as centrifuge tube (EP pipes).
1. first component structure
1.1. first component overall structure
It is illustrated in figure 2 microlayer model and generates chip structure schematic diagram.From left to right, it is designed on an octagonal chip
8 microlayer model generation units 11, in the chips the heart have a centre bore 12, which comes from CD processing technology, uses
The transhipment of substrate during injection injection molding material and mass production.Typical round compact disk structure is not easy to position, by chip plus
Work is eight-sided formation, and processes two location holes 13, is convenient for the location fit of microlayer model chip and relevant device.At center
Hole both sides respectively equidistantly arrange 4 identical microlayer model generation units 11, be used for parallel generation microlayer model.
As shown in Fig. 2, each drop formation unit 11 includes from top to bottom：Oil phase sample inlet 111, hollow flow resistance area
112,115, two oil phase sample inlets, 113, two oil phase filtering areas 114, aqueous sample entrance aqueous sample filtering areas
116, an aqueous sample pipeline 117, microlayer model generation area 118, microlayer model generate observation area 119 and generate microlayer model outlet
1110.Microlayer model as shown in Figure 2 generates chip and is corrected to the normal structure of general disc, can utilize light to greatest extent
The space of disk, 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 design, quickly, reliably generate uniform micron dimension " Water-In-Oil " microlayer model.
1.2. oil phase sample pipetting volume structure
As shown in Figure 3 and Figure 4, 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 12.As shown in figure 3, two oil phase samples
Respectively enter an oil phase filtering area 114 in quality control road 113.Oil phase filtering area 114 is one group of columnar arrays structure.Such as Fig. 4 institutes
Show, columnar arrays structure has multiple rows of columnar arrays staggered.Impurity present in oil phase (particle, silk wadding fiber etc.) is blocked
At this group of column structure, the generation of microlayer model is not influenced.
1.3. aqueous sample is loaded structure
As shown in figure 5, first with external air pump or peristaltic pump, aqueous sample is injected into aqueous sample entrance 115.
It is designed similar to oil phase sample feeding, aqueous sample enters an aqueous sample filtering area 116 and an aqueous sample pipeline
117.Filtering area 116 is one group of columnar arrays structure, it is therefore an objective to filter the impurity in aqueous sample, eliminate impurity and drop is given birth to
At influence.
1.4. microlayer model generates plot structure
As shown in fig. 6, two oil phase sample inlets 113 and an aqueous sample pipeline 117 are in 118 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 117 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.
In some embodiments, as shown in fig. 7, two oil phase sample inlets 113 (are the systems of 113a/113b/113c
Claim) and an aqueous sample pipeline 117 (being the general designation of 117a/117b/117c) microlayer model generation area 118 formed deformation
" cross " structure is used for the generation of microlayer model.
The size of cross structure determines the size of microlayer model.It is micro- that oil phase sample and aqueous sample respectively enter oil phase
Before drop formation pipeline 113a and aqueous phase droplets generate the cross structure of pipeline 117a compositions, oil phase main pipeline 113c and water phase
The size of main pipeline 117c is more than the size that oil phase microlayer model generates pipeline 113a and aqueous phase droplets generate pipeline 117a.This practicality
It is novel that oil phase buffering pipe 113b, water phase supervisor are set between oil phase main pipeline 113c and oil phase microlayer model generate pipeline 13a
Road 117c and aqueous phase droplets generate the water phase buffering pipe 117b being arranged between pipeline 117a.Oil phase buffering pipe 113b and water phase
It is trapezoidal shape on the sections buffering pipe 117b, the outer wall and oil phase microlayer model of oil phase buffering pipe 113b generate outside pipeline 113a
It is obtuse angle that outer included angle is formed between wall；Equally, water phase buffering pipe 117b outer walls and water phase microlayer model generate pipeline 117a
It is obtuse angle that outer included angle is formed between outer wall.If above-mentioned angle is equal to or less than 90 degree, it might have gas residue and exist
Edge dead volume.The reason is that since gas is compressible, this gas residue can cause drop formation unstable.In addition above-mentioned to be equal to
Or it is less than 90 degree, it is unfavorable for chip demoulding processing.Consider that above-mentioned angle is preferably 120-150 degree from above-mentioned two factor,
This angular range drop formation is more stable and more conducively device demoulding is processed.
1.5. observation area and microlayer model collection opening structure
As shown in figure 8, microlayer model generates 119 purpose of observation area it is easy for that optical system is coordinated to monitor microlayer model in real time.It is micro-
The feature structure of drop formation observation area 119 is to design closed micro-structure on the microchannel left side.Due in the enclosed construction
It is not passed through oil phase/water phase liquid, microlayer model, stable still image is collected convenient for Systems for optical inspection, focuses on microchannel
Plane, to obtain clearly testing result.The microlayer model of generation is by generating 1110 outflow of microlayer model outlet.
1.6. 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 12 comes from CD processing technology, for injecting injection molding material and mass production process
The transhipment of middle substrate.Typical round compact disk structure is not easy to position.Therefore, it is eight-sided formation by chip manufacture, and processes two
A location hole 13 is convenient for the location fit of microlayer model chip and relevant device.
2. second component structure
Second component 2 is to realize that " oil phase " sample, the sample introduction of " water phase " sample and microlayer model are collected.As shown in figure 9,
In the present embodiment, corresponding with 8 microlayer model generation units of the first component, 8 microlayer models are arranged in parallel on second component 2
Sample-adding and collector unit, from left to right, each microlayer model is loaded and the equidistant arranged in parallel of collector unit is on second component 2,
Each microlayer model sample-adding and collector unit are matched with each microlayer model generation unit, be used for the water phase of microlayer model generation unit with
The addition of oil sample sample and the microlayer model after generation are collected.It is set above each microlayer model sample-adding and collector unit of second component 2
It is equipped with oil phase sample pipetting volume slot 21, oil phase sample-adding through-hole 22, aqueous sample loading slot 23 and water phase sample-adding through-hole 24, wherein oil phase
Sample-adding through-hole 22 and water phase sample-adding through-hole 24 are separately positioned in 23 bottom of oil phase sample pipetting volume slot 21 and aqueous sample loading slot
Centre；The each microlayer model sample-adding in 2 lower section of second component and collector unit are provided with sample collection device 25, in sample collection device 25
Both ends, which are respectively arranged with, generates microlayer model receiving port 26 and microlayer model collection outlet 27.
In some embodiments, observation window 210 is set on second component 2, for coordinating optical system to monitor life in real time
At microlayer model.Observation window 210 is hollow design, and observation window 210 is located at before generating microlayer model receiving port 26, is able to observe that
The microlayer model that the first component 1 generates.
As shown in Figures 9 and 10, the generation microlayer model receiving port 26 of sample collection device 25 be with generated in the first component 1 it is micro-
1110 corresponding through-hole of drop outlets；It is provided with the storage chamber 28 that prestores after generating microlayer model receiving port 26, after the storage chamber 28 that prestores
Microlayer model collects outlet 27 and is set as the outlet with oblique side wall construction, is provided with the connection for being connect with EP pipes at its end
Bar 29, connecting rod 29 have curved wall.Connecting rod 29 is goed deep into inside EP pipes, is collected convenient for microlayer model.
The microlayer model that is generated in the first component 1 is under pressure by generating microlayer model outlet 1110 and second component
Droplet inlet 26 is generated, into the storage chamber 28 that prestores, the density of microlayer model is less than oil phase sample, the top of oil can be floated on, with micro-
The continuous inflow of drop and oil, the oblique side wall that microlayer model can collect outlet 27 along microlayer model slide into EP pipes.
In some embodiments, the first component 1 and second component 2 are loaded through-hole in oil phase sample inlet 111 and oil phase
22, aqueous sample entrance 115 and water phase are loaded through-hole 24, generate microlayer model 1110 through-holes of outlet and generation droplet inlet 26 is respective
Glue of around punctuating seals.
Two, microlayer model generates working-flow
Entire workflow is divided into three steps：(1) sample feeding step, (2) microlayer model generation step, and (3) micro- liquid
Drip collection step.First, " oil phase " sample and " water phase " sample are added into 21 He of oil phase sample pipetting volume slot of second component 2
Aqueous sample loading slot 23.By means of external pressure, two kinds of samples pass through oil phase sample-adding through-hole 22 respectively and water phase is loaded through-hole
24, have respectively entered the oil phase sample inlet 111 and aqueous sample entrance 115 of the first component 1.
After oil phase sample enters oil phase sample inlet 111, in order to accurately control oil phase sample injection volume, in oil phase sample
Back-shaped flow resistance area 112 is devised after entrance 111, which is made of multiple U-tube roads.Oil phase sample meeting
Infiltration is in surface of polymer material, and in the case where not applying pressure condition, by capillarity, oil phase sample automatically flows into microchannel
In.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 constant flow of the oil phase sample under capillary action in microchannel to the greatest extent so that oil phase sample
Sample size 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 12.In two oil phase sample inlets 113
Respectively enter an oil phase filtering area 114.Oil phase filtering area 114 is one group of columnar arrays structure, and columnar arrays structure has multiple rows of
Columnar arrays staggered.Impurity present in oil phase (particle, silk wadding fiber etc.) is blocked at this group of column structure, not shadow
Ring the generation of microlayer model.
After aqueous sample is injected into aqueous sample entrance 115, it is similar to oil phase sample feeding and designs, aqueous sample enters
One aqueous sample filtering area 116 and an aqueous sample pipeline 117.Filtering area is one group of columnar arrays structure, it is therefore an objective to mistake
The impurity in aqueous sample is filtered, influence of the impurity for drop formation is eliminated.
Oil phase and water phase form uniform microlayer model in the microlayer model generation area 118 of the first component 1.The microlayer model of generation
By the generation droplet inlet 26 for generating microlayer model outlet 1110 and second component of the first component 1, into the pre- of second component
The microlayer model of storage chamber 28, the storage chamber 28 that prestores enters the EP being connected on sample collection device pipes by collecting outlet 27, completes
The generation and collection of microlayer model.
(1) sample feeding step
Oil phase sample and aqueous sample are previously placed in the oil phase sample pipetting volume slot 21 and aqueous sample sample-adding of second component 2
In slot 23.External pressure effect under, two kinds of samples respectively pass through oil phase sample-adding through-hole 22 and water phase be loaded through-hole 24, respectively into
Enter the oil phase sample inlet 111 and aqueous sample entrance 115 to the first component 1；Oil phase enters two-way oil phase sample inlet later
113, water phase enters aqueous sample pipeline 117 all the way.
(2) microlayer model generation step
" oil phase " sample flows into micron level pipeline from horizontal direction under extraneous gas pressure；" water phase " sample is outside
Under boundary's gas pressure, micron level pipeline is flowed into from vertical direction.Two kinds of immiscible liquid are at " cross " microfluidic structures
It crosses.Shearing force caused by surface tension of liquid difference and impressed pressure due to " oil phase " sample and " water phase " sample, " water
Phase " sample is divided into discrete microlayer model from continuous phase at cross structure by " oil phase " sample.Microlayer model is " Water-In-Oil "
Form, outside are " oil phase " samples.
(3) microlayer model collection step
The microlayer model of generation is by the generation microlayer model outlet 1110 of the first component 1 and the generation droplet inlet of second component
26, into the storage chamber 28 that prestores of second component, the microlayer model for the storage chamber 28 that prestores is received by collecting outlet 27 into sample is connected to
EP pipes on acquisition means, complete the generation and collection of microlayer model.
Microlayer model flows to the microlayer model outlet of the first component 1 as seen from Figure 5 after being generated in first component microchannel
15 and second component generation droplet inlet 26, drop floats to the storage chamber 28 that prestores of second component 2, micro- liquid under pressure
The density of drop is less than oil phase sample, can float on the top of oil, and with the continuous inflow of microlayer model and oil, microlayer model can be along collection
The oblique side wall of outlet 27 slides into EP pipes, and connecting rod 29 is goed deep into inside EP pipes, is collected convenient for microlayer model.
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 (23)
1. a kind of microlayer model generates system, it is characterised in that：
It includes the first component and second component that the microlayer model, which generates system, and the first component is fixedly connected with second component；It is described
The first component is that microlayer model generates chip, is used for the generation of microlayer model；The second component is microlayer model sample pipetting volume and generation
Microlayer model collection device, the collection of the microlayer model of the sample-adding and generation of the oil phase sample and aqueous sample for the first component；
It includes a centre bore that the microlayer model, which generates chip, and the centre bore generates chip fabrication process for the microlayer model
Microlayer model generates the transhipment of chip during middle injection injection molding material and mass production；The centre bore both sides are with centre bore
Centrally disposed one or more microlayer model generation unit, each microlayer model generation unit have independently produced microlayer model；With
The second component is provided with and each matched microlayer model of microlayer model generation unit is loaded and collector unit, often
Sample-adding, generation and the receipts of the microlayer model sample-adding and collector unit cooperation progress microlayer model of a microlayer model generation unit corresponding thereto
Collection.
2. microlayer model according to claim 1 generates system, it is characterised in that：The first component and the second component
It is sealedly and fixedly connected by dispensing mode or ultrasonic welding mode.
3. microlayer model according to claim 1 generates system, it is characterised in that：The first component and the second component
It is formed respectively by integrated injection molding.
4. microlayer model according to claim 1 generates system, it is characterised in that：The first component and the second component
It is thermoplastic material.
5. microlayer model according to claim 4 generates system, it is characterised in that：The thermoplastic material is makrolon material
Material, cyclic olefine copolymer or polymethyl methacrylate, polypropylene.
6. microlayer model according to claim 1 generates system, it is characterised in that：There are four first component settings, eight
A or 12 microlayer model generation units；The second component is provided with corresponding four, eight or 12 microlayer model lifes
At unit.
7. microlayer model according to claim 1 generates system, 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.
8. microlayer model according to claim 7 generates system, 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.
9. microlayer model according to claim 7 generates system, it is characterised in that：The microlayer model generation unit includes two
Oil phase micro-pipe road and a water phase micro-pipe road or an oil phase micro-pipe road and two water phase micro-pipe roads；Oil phase micro-pipe road and
Water phase micro-pipe road forms criss-cross construction, is used to form microlayer model.
10. microlayer model according to claim 9 generates system, it is characterised in that：Pipe after the oil phase sample inlet
It is provided with hollow flow resistance area in road, after oil phase sample flows through hollow flow resistance area, is divided into two-way and respectively enters oil phase sample cell
Road generates " Water-In-Oil " microlayer model；Or hollow flow resistance area, water phase sample are provided in the pipeline after the aqueous sample entrance
After product flow through hollow flow resistance area, it is divided into two-way and respectively enters aqueous sample pipeline, generate " oil-in-water " microlayer model.
11. microlayer model according to claim 7 generates system, 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.
12. microlayer model according to claim 11 generates system, 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.
13. microlayer model according to claim 7 generates system, 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.
14. microlayer model according to claim 1 generates system, it is characterised in that：It is provided with oil above the second component
Phase sample pipetting volume slot, oil phase sample-adding through-hole, aqueous sample loading slot and water phase are loaded through-hole, wherein oil phase sample-adding through-hole and
The water phase sample-adding through-hole is separately positioned in the oil phase sample pipetting volume slot and aqueous sample sample-adding trench bottom, the oil
Phase sample and the aqueous sample enter the first component by them respectively；Second component lower section is provided with sample
Collection device.
15. microlayer model according to claim 14 generates system, it is characterised in that：The oil phase sample pipetting volume slot and described
The volume of aqueous sample loading slot is respectively 1~900 microlitre.
16. microlayer model according to claim 15 generates system, it is characterised in that：The oil phase sample pipetting volume slot and described
The volume of aqueous sample loading slot is respectively 5~500 microlitres.
17. microlayer model according to claim 16 generates system, it is characterised in that：The oil phase sample pipetting volume slot and described
The volume of aqueous sample loading slot is respectively 100~200 microlitres.
18. microlayer model according to claim 14 generates system, it is characterised in that：The sample collection device is included in it
The generation microlayer model receiving port and microlayer model collection port that both ends are respectively set, and the storage chamber that prestores；What the first component generated
Microlayer model enters second component by the microlayer model receiving port, then passes through the storage chamber that prestores, and finally from micro- liquid
Drop collection port is collected.
19. microlayer model according to claim 18 generates system, it is characterised in that：The microlayer model collection port is set as having
The outlet for having oblique side wall construction, is provided with connecting rod at its end, and microlayer model instills microlayer model collection vessel through the connecting rod
In.
20. microlayer model according to claim 19 generates system, it is characterised in that：The microlayer model collection vessel is centrifugation
Pipe, the connecting rod have curved wall；The connecting rod is goed deep into inside the centrifuge tube, is collected convenient for microlayer model.
21. generating system according to any microlayer models of claim 1-20, it is characterised in that：The microlayer model generates system
Further include third member, the third member seals the oil phase sample and aqueous sample of the second component, and passes through its application
External pressure.
22. generating system according to any microlayer models of claim 1-20, it is characterised in that：The first component and described
It is also respectively provided on second component and is fixedly connected with the location hole positioned convenient for the two.
23. generating system according to any microlayer models of claim 1-20, it is characterised in that：It is arranged on the first component
Microlayer model generates is arranged observation window on observation area and the second component, for coordinating optical system to monitor micro- liquid of generation in real time
Drop.
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| CN201721460417.1U CN207981204U (en) | 2017-11-06 | 2017-11-06 | Microlayer model generates system |
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| CN201721460417.1U CN207981204U (en) | 2017-11-06 | 2017-11-06 | Microlayer model generates system |
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ID=63804642
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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. |