CN104741158B - A kind of method and apparatus generating microlayer model using inertia force - Google Patents
A kind of method and apparatus generating microlayer model using inertia force Download PDFInfo
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Abstract
A kind of device and method that microlayer model is generated by inertia force.Apparatus main body includes acceleration generation device, is used to generate centripetal acceleration；First liquid；Droplet treatment device, has microchannel, and the first liquid generates the drop of 5-300 μ m diameter under the action of acceleration generation device by the microchannel of droplet treatment device；Collection device is used to collect the drop of generation；Wherein, the first liquid is in hydrophobic state on the surface of droplet treatment device exit portion.The production method customer service of this new microlayer model deficiency of conventional method, the residual of no surface liquid, may be implemented it is high-throughput quickly generate microlayer model, and the controllability dispersion of drop may be implemented.
Description
Technical field
The present invention relates to field of biotechnology, are more particularly to the generation device and method of a kind of microlayer model, and its application.
Technical background
In recent years, biotech development proposes increasingly higher demands to droplet treatment technology: in a first aspect, the low loss of sample
Demand.For example unicellular sample (such as fertilized eggs) of microsequencing sample, section sample, the rare sample of cancer (such as CTC cell) sample
In the preparations of product, characterization technique, the integrality of biological sample is kept to be even more important.And for digital PCR, digital
Other digital quantitative technologies such as MDA keep the integrality of sample up to the necessary condition that 99% or more is even more technology, i.e., at sample
It needs to guarantee sample loss few as far as possible in reason, detection process.However, using the droplet treatment skill of traditional microfluidic chip solution
Art inevitably generates droplet treatment medium residual, and nucleic acid, albumen in sample is caused to wait analysis component loss.
Second aspect, uniformity demands.These for micro-example precision system is standby, detection technique, and need to generate
Droplet size is uniform, cannot again excessive difference, cause to bring tendentiousness and uncertainty in subsequent experimental.
The third aspect, high-throughput demand.With being increasing for upstream sample number, the need that extensive sample is prepared simultaneously
Ask continuous growth.Existing micro flow chip technology generates the technology of drop, and every instrument is at most only capable of making 8 samples drop simultaneously
Change, due to its cumbersome pipe design, fluid control design case is no longer satisfied expansion scale, the needs of flux.
Fourth aspect, refrigeration demand.Biological sample, especially DNA, RNA, protein sample are more fragile.Also, some are anti-
It after answering liquid to configure, will react under room temperature (such as MDA), need quick (< 10min) (Celsius less than 10 in low temperature
Degree, preferably at 0-4 degrees Celsius) generate drop.Conventional method cannot easily cool down to micro flow chip, and generate speed
Also not fast enough.
When liquid is very small, the characteristic completely different with macroscopical liquid is shown.Such as face size 10
In × 10 μm of microchannels, fluid is in laminar condition, the macrofluid of heat transfer and mass transfer all with routine, such as common laboratory
It is different in beaker or the rubber tube of 1 centimetre of end face.All the time, quickly the accurate drop for generating micron level is a Xiang Ju great
Engineering challenge.Micro-fluidic chip can quickly generate the drop of controlled diameter, but its device is complicated, higher cost.Ink-jet
Technology can produce the drop of high speed, but its liquid-drop diameter uniformity is bad, and needs ink discharge device, be not suitable for commonly
Biochemistry Experiment room.Therefore, development easily quickly generates uniform droplet, such as 300 microns hereinafter, have very heavy
The Biochemical Significance wanted.
The technology of the drop provided by the invention generated based on high inertia force, meets above-mentioned 4 demands well.1)
Noresidue.Whole drops, completely via droplet treatment mouth, generate drop, will not generate residual in the high centrifugal force field of centrifuge.
2) controllable monodisperse.The equilibrium state that whole drops generate drop is all the same, so drop size is accurately identical, and repeatability
Good, controlled range is big, influences without liquid turbulence etc..3) high-throughput.Due to only centrifugal force being needed to can produce drop, it is only necessary to one
Centrifuge (such as thermo PICO17, PICO 21, eppendorf 5430R etc.), is received using 1.5mL centrifuge tube on platform routine table
Collection can make the droplet treatment of 24 samples simultaneously, if further using 8 townhouse pipes, 96 orifice plates, 384 orifice plates, even 1536 holes
The form of plate, and be stacked, it is easy to a desk centrifuge is used, while realizing the liquid of thousands of or even up to ten thousand independent samples
Dropization.
Summary of the invention
In view of the deficiencies of the prior art, the present invention proposes a kind of big aqueous phase droplets such as simple to generate new method.Using used
Property power drive droplet treatment medium, pass through microchannel, be broken after flow out airway mouth, generation drop and is fallen in trapping medium.With
The liquid for generating drop contact can be air or the out-phase of low-density.
Fracture of drop under the conditions of inertia force meets a specific physical process: the terrestrial gravitation suffered by the drop is big
When the surface tension of most weakness, drop fracture.Using determining inertia force constant, this principle is commonly utilized in measurement
On solution surface tension, referred to as drip method, size is by 0.5-2mm etc..And the inertia force and adjustment tension of variation are used, come high
Speed generates small size, and the principle of surface tension is not only utilized, more for wide bioid in the drop of 5-200 μ m diameter
Learn meaning.Uniform fine droplet has huge potentiality in the context of detection of biology or chemistry.
In the present invention, so-called acceleration is referred under the action of extraneous non-natural power, such as centripetal force, tractive force,
So that the power that liquid is contrary by acceleration, so that the oriented trend in contrast to the movement of acceleration direction of liquid.This
In invention, effect of first liquid by inertia force forms drop by droplet treatment device.First liquid is also referred to as droplet treatment
Medium.
A kind of generation device of drop of the present invention, which is characterized in that include acceleration generation device, be used to generate centripetal
Acceleration；Include the first liquid；Comprising droplet treatment device, have microchannel, work of first liquid in acceleration generation device
The drop of 5-300 μ m diameter is generated with the lower microchannel by droplet treatment device；Comprising collection device, it is used to collect generation
Drop；Wherein, the first liquid is in hydrophobic state on the surface of droplet treatment device exit portion.Wherein the internal diameter of the microchannel is 1-
100 μm, length 0.1-10mm.
The present invention provides a kind of production method of drop, which is characterized in that includes acceleration generation device, is used to generate
Centripetal acceleration；Include the first liquid；Comprising droplet treatment device, has microchannel, the first liquid is in acceleration generation device
Under the action of the drop of 5-300 μ m diameter is generated by the microchannel of droplet treatment device；Comprising collection device, it is used to collect production
Raw drop；Wherein, the first liquid is in hydrophobic state on the surface of droplet treatment device exit portion.The wherein internal diameter of the microchannel
It is 1-100 μm, length 0.1-10mm.
Wherein the first liquid refers to the liquid or solution of common low viscosity.Such as first liquid be water, cell culture
It include the combination of cell, DNA, RNA or protein in the solution or liquid of the substances such as liquid, ethyl alcohol.
Droplet treatment device is the device with microchannel.Such as common capillary, narrow meshed film or narrow meshed plate；
The internal diameter of capillary or the diameter of aperture are 1-100 μm；The material of droplet treatment device can be for inorganic material such as: glass, quartz,
Silicon；Or common organic plastic material is such as: polystyrene, polycarbonate, polymethylacrylic acid, polyamide, polyethylene, polychlorostyrene second
Alkene, polypropylene；Fluoro-containing plastic such as polytetrafluoroethylene (PTFE), PVDF etc..
According to further preferred technical solution, the aperture is circular hole or polygonal hole；The internal diameter of the square hole is
Its side length is 1-100 μm.
According to further preferred technical solution, the diameter of the drop is 10-250 μm, preferably 20-200 microns；It is described
The internal diameter of microchannel is 2-90 microns, preferably 5-50 microns；The length of microchannel is 0.5-6mm, preferably 1-5mm.
According to further preferred technical solution, droplet treatment device is 1,2 ... ..n, wherein n is greater than 2 integer.
According to further preferred technical solution, collection device is that pipe is collected by centrifugation.
According to further preferred technical solution, it further can also include the storage device of the first liquid, be used for
Store the first liquid.
It can also include further second liquid, be located in collection device, for collecting the liquid of the first liquid generated
Drop, the part of the outlet of the droplet treatment device and second liquid do not contact.First liquid is before being converted to drop and is converted to
It is not contacted with second liquid in drop.
According to further preferred technical solution, the acceleration generation device is centrifuge.
According to further preferred technical solution, the acceleration can be constant or variation.
According to further preferred technical solution, the microchannel is straight or curved.
According to further preferred technical solution, droplet treatment device is the tube or cone that there is opening in front end.
It further include delay medium or deferred mount according to further preferred technical solution.
According to further preferred technical solution, droplet treatment device and storage device are an entirety.
According to further preferred technical solution, droplet treatment device materials are inorganic material, organic material or composite material.
Inorganic material is glass, quartz, ceramics, one of metal.Organic material is polystyrene, polyether-ether-ketone, polyester macromolecule
One of material.Composite material is the mixture of one or more organic materials and/or inorganic material.
According to further preferred technical solution, the whole of the droplet treatment device or only exit portion are by hydrophobic
And/or Hydrophilic Surface Treatment, so that the first liquid is in hydrophobic state on the surface of droplet treatment device exit portion；The side of surface treatment
Method has: directly covering painting, chemical reaction modification, chemical deposition etc..
It according to demand, can not include the storage device of the first liquid, such as using capillary as droplet treatment device, hair
Tubule can inherently store a certain amount of liquid, as shown in Figure 1.It according to demand, can further include the first liquid
Storage device can be the material different with droplet treatment device；It is also possible to material identical with droplet treatment device, and can
To form an entirety with droplet treatment device.
Second liquid is also referred to as trapping medium, mainly there is following effect:
(1) it does not dissolve each other with water phase.
(2) buoyancy is provided, the gravity that drop receives is greatly decreased, keeps the drop generated not because centrifugal force ruptures, fusion.
(3) viscosity is provided, drop decrease speed is reduced, drop is buffered, avoids merging.
Activating agent, stable droplet are provided.
(4) density is less than droplet treatment phase, and aqueous phase droplets can be allowed to be deposited to trapping medium bottom, avoid newly generating with top
Dripping drops collision, generate fusion.
(5) prevent moisture from evaporating.In subsequent experimental, as prevented moisture from evaporating during PCR
(6) image forming medium, subsequent analysis, the mobile phase of fluorescent collecting etc. are used as.
Device, that is, droplet treatment device of drop is generated, simplest droplet treatment device is capillary.Capillary can be by one
Root or a plurality of composition.It can be constituted by a capillary or mostly with capillary, porous capillary or perforated membrane, porous can also be used
Plate, as shown in Figure 2.
The manufacture of tubule can be drawn after machining by being machined, wet etching, and the techniques such as dry etching are configured with
The processes such as cutting, polishing are completed.
Tubule materials can be for inorganic material such as: glass, quartz, silicon；Or common organic plastic material is such as: polystyrene, gathers
Carbonic ester, polymethylacrylic acid, polyamide, polyethylene, polyvinyl chloride, polypropylene；Fluoro-containing plastic such as polytetrafluoroethylene (PTFE), PVDF
Deng.
Tubule or tubule group surface need to modify, and the result of modification should make droplet treatment medium be unlikely to spread in micro-pipe nozzle
It opens.Droplet treatment medium and the contact angle on surface should be greater than 90 degree.
The device overall structure is divided into three parts.Droplet treatment device (on), collecting pipe (under) two parts composition；Droplet treatment pipe
Area and micro-pipe area two parts are held comprising drop.
The effect of droplet treatment device is temporarily to hold droplet treatment medium and generate drop using microcosmic and high inertia force.Its table
Face should have low adsorption or so to held droplet treatment medium (usually water phase) and solute.Droplet treatment pipe bottom is micro-pipe
Area, micro-pipe area and holding are fully sealed between area, can be bonded or be integrated, so that under inertia force effect, all drops
Change medium completely extends across micro-pipe and gets in collecting pipe.
Collecting pipe can be conventional centrifuge tube or orifice plate, or special matched collecting pipe.Trapping medium is held in collecting pipe,
Usually inert organic solvents, and density is less than droplet treatment medium.Trapping medium page height must not be excessively high, cannot contact micro-
Area under control lower end；Trapping medium can not be very few, it is necessary to can effectively collect the drop fallen.Usual trapping medium is that droplet treatment is situated between
10 times or more of matter total amount.
Inertia force is so that the first liquid generates the power of microlayer model by the microchannel of droplet treatment device.Common inertia
There are many kinds of power, such as can be with the droplet treatment device and collecting pipe described in human hand held, and whipping can promote liquid to pass through back and forth
The microchannel of certain size generates drop, but it can not generate uniform drop, not be able to satisfy actual application.It can incite somebody to action
Droplet treatment device is mounted in the bottom of rocking equipment along the centripetal direction of rocking equipment.Rotating device, such as centrifuge can be with
Stable inertia force is provided.
Delay start design.Because inertia force not up to balances in accelerator, the drop of generation is uneven.In order to
Completely make the big drops such as whole droplet treatment media generations, it is necessary to not generate liquid in the accelerated period of acceleration generation device
Body.Implementation has two classes: 1, increase device, the openable organ of, such as seals with wax such as under certain inertia force；Or 2, increase by one
Kind high viscosity high density liquid is being held in pipe, and this liquid is first flowed out from micropore, and the liquid for really needing droplet treatment is protected
Top is stayed in, is blocked and flows out again for a period of time.Residence time is determined by the volume of addition high density liquid.Retardance liquid should have
Following feature: 1, droplet treatment medium of getting along well is miscible or reacts, and has enough chemical inertnesses.2, do not generate drop or generate
Drop cannot merge or generate drop and can distinguish and separate, and be not involved in subsequent reactions.It 3, can be miscible with collection liquid.
The principle that drop generates can be explained by following calculating:
Critical state equation:
2 π r γ=Gm...... (1)
γ: surface tension, unit (mN.m)；R: microchannel diameter.Unit (m)；G: centrifugation force value.Unit (N/m2)；M:
Drop mass.
The density formula of liquid:
V: droplet size.R: liquid-drop diameter.ρ: droplet density.
(2) it brings into (1) and obtains:
However, repeatedly generation etc. is big if under given conditions, the inertia force that adjustable drop is subject to can be continuous
Drop.Also, by adjusting: it γ, G, r, ρ, can adjust droplet size (V), to change the drop of unit liquid volume
Number.
The adjustment of surface tension γ.By adding ion, bioactive agent composition in water phase, γ can be reduced, drop is made to become smaller.
Activating agent can be Span activating agent, Tween activating agent, triton activating agent, fluorine-containing surfactant, such as EA activating agent, perfluor
Octanoic acid, perfluor amide etc..γ is proportional to V
The adjustment of G.The size for adjusting inertia force can adjust the size of G especially by the revolving speed of adjustment centrifuge, and G is logical
Often at 1,000-1,000,000m/s2 (0.1-100krcf).1/G is proportional to V.
The adjustment of r.Adjust microchannel size, thus it is possible to vary droplet size.Smaller microchannel diameter can produce smaller
Drop.R is proportional to V.
The adjustment of ρ fluid density.Such as increase glucose, the solutes such as glycerol, adjustable water density 1.0-1.2g/mL.1/ρ
It is proportional to V.
Drop generate speed be it is adjustable, because of the limitation of revolution.Flow velocity, revolution and flow resistance have following relationship.
The pressure difference p of its volume flow Q and pipe both ends, the relationship of flow resistance R:
Q=p/R
Pressure difference p is in inertia force G, the relationship of page height h and fluid density ρ:
P=ρ Gh
The flow resistance R of laminar flow round pipe liquid calculates as follows:
In above formula: the coefficient of viscosity η (cst) of the radius r of micro-pipe, length L and fluid.
By adjusting flow resistance R, acceleration G, liquid level.Can adjust drop generate speed, thus change experiment it is total when
Between.
Adjust L capillary pipe length.Design adjustment.It is optional from 10 μm of -10mm.
Adjust r capillary radius.Different size is optional.From 1-100 μm.
Adjust the viscosity of the first liquid of η.Temperature is lower, and viscosity is bigger.
The drop that the method provided by the invention for generating drop generates is uniform, and device is simple, can be with direct combination to centrifugation
It is used in the equipment such as machine.By experiment, we are had surprisingly found that, if the first liquid is on the surface of droplet treatment device exit portion
It cannot be in hydrophobic state, then can not generate monodisperse drop.When the outlet of droplet treatment device does not contact second liquid, generate
Drop have better uniformity.The drop uniformity of generation is good, and can accomplish very high flux.
Detailed description of the invention
Fig. 1, the production principle of drop.
Fig. 2, single dropproducing devices and multiple dropproducing devices schematic diagrames.
Fig. 3, the dropproducing devices and multiple integrated dropproducing devices schematic diagrames individually integrated.
Fig. 4 generates the result figure of drop.
Fig. 5, physics time-delay mechanism schematic diagram.
Specific embodiment:
Specific embodiment in the specific embodiment of the invention, only for further explanation of the invention, and not enough
At limiting factor of the invention.
Embodiment 1
Using eppendorf5430R centrifuge as acceleration generation device, the first liquid is used water as, hair is utilized
Thin glass tube does surface modification with trichlorine perfluoro silane as droplet treatment device, the exit of capillary；In the pipe of centrifuge tube
Pass through processing one and storage device of the matched droplet treatment pipe of centrifuge tube as the first liquid at mouthful.In the outside of droplet treatment pipe
Son is covered for sealing.Droplet treatment pipe is added in first liquid, is packed into centrifuge after being installed on centrifuge tube.It utilizes
Pipe is collected by centrifugation as collection device in eppendorf 2mL.Using 500 μ L mineral oil, (addition tween80 and span80 is as work
Property agent) be used as second liquid.The diameter distribution that the drop under different parameters can be obtained is as shown in table 1.Droplet treatment device such as Fig. 3
Shown in leftmost diagram.
The related table (γ=60mN/m) of 1 revolving speed of table, microchannel size and microlayer model diameter
Embodiment 2.
Select capillary as droplet treatment device, the internal diameter of capillary is 10 microns, and length is 5 millimeters, utilizes thermo
For PICO17 centrifuge as inertia force generating apparatus, collection device is that pipe, the exit trichlorine perfluor of capillary is collected by centrifugation
Surface modification is done for silane.First liquid selects water, passes through processing one and the matched liquid of centrifuge tube at the nozzle of centrifuge tube
Storage device of the dropization pipe as the first liquid.Son is covered for sealing in the outside of droplet treatment pipe.Liquid is added in first liquid
Dropization pipe is packed into centrifuge after being installed on centrifuge tube.The centrifugal force of centrifuge is set as 3KG, and centrifuge generates centripetal force
Direction is identical with the direction of capillary.
Utilize mineral oil as trapping medium.The diameter for the drop being collected into is 48 μm, CV 3%.The part liquid of generation
Drop is as shown in Figure 4.
Embodiment 3.
Other conditions and embodiment 2 are identical, and wherein the surface free of capillary crosses modification.Generate drop diameter be about
145 μm, CV 30%.
Embodiment 4.
Other conditions and embodiment 1 are identical, wherein selecting 96 hole PCR plates is that pipe is collected by centrifugation, and is furnished with capillary with self-control
96 orifice plates as droplet treatment pipe,
Embodiment 5.
Other conditions and embodiment 1 are identical, wherein droplet treatment device is the capillary group of 100 capillaries composition.It generates
The diameter of drop is 48 μm, CV 3%
Embodiment 6.
Other conditions and embodiment 1 are identical, wherein it has fluid collection device i.e. collecting pipe, has integrated liquid
Drop makeup is set, i.e., droplet treatment pipe in figure, multiple outlets are arranged at the lower part of droplet treatment pipe.8 droplet treatment devices can form 8 townhouse shapes
Formula can also form 96 well formats, as shown in Figure 3.
Embodiment 7.
Other conditions are identical with embodiment 1, wherein delayed startup device injects as shown in figure 5, will be collected below in pipe
100uL trapping medium mineral oil.Pipe will be held to be inserted in collecting pipe.By high viscosity fluorocarbon oil (such as Dupont GPL100 series and
VPF series fluorocarbon oil) 3uL injection holds pipe, then the injection of 20uL droplet treatment medium is held pipe.It closes the lid.
Embodiment 8.
Other conditions are identical with embodiment 1, wherein and the outlet of droplet treatment device is located under the liquid level of second liquid,
That is the first liquid directly contacts second liquid after leaving outlet.The liquid-drop diameter of generation is about 120 microns, and CV is
15%.
Claims (28)
1. a kind of dropproducing devices, which is characterized in that include acceleration generation device, be used to generate centripetal acceleration；The
One liquid；Droplet treatment device, has microchannel, and the first liquid passes through droplet treatment device under the action of acceleration generation device
Microchannel generate 5-300 μ m diameter drop；Collection device is used to collect the drop of generation；Wherein, the first liquid is in liquid
Drop makeup sets the surface of exit portion in hydrophobic state；Wherein the internal diameter of the microchannel is 1-100 μm, length 0.1-10mm；
Storage device comprising the first liquid is used to store the first liquid；Comprising second liquid, it is located in collection device, for receiving
Collect the drop of the first liquid generated, the part of the outlet of the droplet treatment device and second liquid do not contact；The acceleration
Degree generation device is centrifuge；The inertia force G that the centripetal acceleration generates is in 0.72-100krcf range.
2. dropproducing devices according to claim 1, which is characterized in that
First liquid is in the solution or liquid of water, cell culture fluid, ethyl alcohol comprising cell, DNA, RNA or protein.
3. dropproducing devices according to claim 1, which is characterized in that
Droplet treatment device is the device with microchannel, is selected from capillary, narrow meshed film or narrow meshed plate；Capillary it is interior
The diameter of diameter or aperture is 1-100 μm；The material of droplet treatment device be inorganic material such as: glass, quartz, silicon；Or common have
Machine plastic material is such as: polystyrene, polycarbonate, polymethylacrylic acid, polyamide, polyethylene, polyvinyl chloride, polypropylene；Contain
Fluoroplastics such as polytetrafluoroethylene (PTFE), PVDF.
4. dropproducing devices according to claim 3, which is characterized in that
The aperture is circular hole or polygonal hole；I.e. its side length is 1-100 μm for the internal diameter of the polygonal hole.
5. dropproducing devices according to claim 1, which is characterized in that
The diameter of the drop is 10-250 μm；The internal diameter of the microchannel is 2-90 microns；The length of microchannel is 0.5-
6mm。
6. dropproducing devices according to claim 1, which is characterized in that
Droplet treatment device is 1,2 ... ..n, wherein n is greater than 2 integer.
7. dropproducing devices according to claim 1, which is characterized in that
Collection device is that pipe is collected by centrifugation.
8. dropproducing devices according to claim 1, which is characterized in that
The acceleration is constant or variation.
9. dropproducing devices according to claim 1, which is characterized in that
The microchannel is straight or curved.
10. dropproducing devices according to claim 1, which is characterized in that
Droplet treatment device is the tube or cone that there is opening in front end.
11. dropproducing devices according to claim 1, which is characterized in that
It further include delay medium or deferred mount.
12. dropproducing devices according to claim 1, which is characterized in that
Droplet treatment device and storage device are an entirety.
13. dropproducing devices according to claim 1, which is characterized in that
Droplet treatment device materials are inorganic material, organic material or composite material；Inorganic material is glass, quartz, ceramics, metal
One of；Organic material is polystyrene, polyether-ether-ketone, one of polyester macromolecule material；Composite material be it is a kind of or
The mixture of a variety of organic materials and/or inorganic material.
14. dropproducing devices according to claim 1, which is characterized in that
The whole of the droplet treatment device or only exit portion pass through hydrophobic and/or Hydrophilic Surface Treatment, so that the first liquid
It is in hydrophobic state on the surface of droplet treatment device exit portion；The method of surface treatment has: directly covering painting, chemical reaction modification is changed
Learn deposition.
15. a kind of drop forming method, which is characterized in that include acceleration generation device, be used to generate centripetal acceleration；The
One liquid；Droplet treatment device, has microchannel, and the first liquid passes through droplet treatment device under the action of acceleration generation device
Microchannel generate 5-300 μ m diameter drop；Collection device is used to collect the drop of generation；Wherein, the first liquid is in liquid
Drop makeup sets the surface of exit portion in hydrophobic state；The internal diameter of the microchannel is 1-100 μm, length 0.1-10mm；Include
The storage device of first liquid is used to store the first liquid；Comprising second liquid, it is located in collection device, is produced for collecting
The drop of the first raw liquid, the part of the outlet of the droplet treatment device and second liquid do not contact；The acceleration produces
Generating apparatus is centrifuge；The inertia force G that the centripetal acceleration generates is in 0.72-100krcf range.
16. drop forming method according to claim 15, which is characterized in that
First liquid is in the solution or liquid of water, cell culture fluid, ethyl alcohol comprising cell, DNA, RNA or protein.
17. drop forming method according to claim 15, which is characterized in that
Droplet treatment device is the device with microchannel, is selected from capillary, narrow meshed film or narrow meshed plate；Capillary it is interior
The diameter of diameter or aperture is 1-100 μm；The material of droplet treatment device be inorganic material such as: glass, quartz, silicon；Or common have
Machine plastic material is such as: polystyrene, polycarbonate, polymethylacrylic acid, polyamide, polyethylene, polyvinyl chloride, polypropylene；Contain
Fluoroplastics such as polytetrafluoroethylene (PTFE), PVDF.
18. drop forming method according to claim 17, which is characterized in that
The aperture is circular hole or polygonal hole；I.e. its side length is 1-100 μm for the internal diameter of the polygonal hole.
19. drop forming method according to claim 15, which is characterized in that
The diameter of the drop is 10-250 μm；The internal diameter of the microchannel is 2-90 microns；The length of microchannel is 0.5-
6mm。
20. drop forming method according to claim 15, which is characterized in that
Droplet treatment device is 1,2 ... ..n, wherein n is greater than 2 integer.
21. drop forming method according to claim 15, which is characterized in that
Collection device is that pipe is collected by centrifugation.
22. drop forming method according to claim 15, which is characterized in that
The acceleration is constant or variation.
23. drop forming method according to claim 15, which is characterized in that
The microchannel is straight or curved.
24. drop forming method according to claim 15, which is characterized in that
Droplet treatment device is the tube or cone that there is opening in front end.
25. drop forming method according to claim 15, which is characterized in that
It further include delay medium or deferred mount.
26. drop forming method according to claim 15, which is characterized in that
Droplet treatment device and storage device are an entirety.
27. drop forming method according to claim 15, which is characterized in that
Droplet treatment device materials are inorganic material, organic material or composite material；Inorganic material is glass, quartz, ceramics, metal
One of；Organic material is polystyrene, polyether-ether-ketone, one of polyester macromolecule material；Composite material be it is a kind of or
The mixture of a variety of organic materials and/or inorganic material.
28. drop forming method according to claim 15, which is characterized in that
The whole of the droplet treatment device or only exit portion pass through hydrophobic and/or Hydrophilic Surface Treatment, so that the first liquid
It is in hydrophobic state on the surface of droplet treatment device exit portion；The method of surface treatment has: directly covering painting, chemical reaction modification is changed
Learn deposition.
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|---|---|---|---|---|
| CN106076443B (en) * | 2016-06-12 | 2019-05-24 | 北京天天极因科技有限公司 | A kind of preparation method of micro channel array plate, the device and drop forming method for using it to obtain drop |
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| CN108587859B (en) * | 2018-04-20 | 2022-03-29 | 杭州兴浩晖生物科技有限公司 | Sample droplet generation system and method |
| CN108587862B (en) * | 2018-04-20 | 2022-02-22 | 杭州兴浩晖生物科技有限公司 | Sample droplet generator |
| CN110760571A (en) * | 2018-08-27 | 2020-02-07 | 浙江达普生物科技有限公司 | Digital quantitative multi-target joint biological detection |
| US11130120B2 (en) * | 2018-10-01 | 2021-09-28 | Lifeng XIAO | Micro-pipette tip for forming micro-droplets |
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| CN111330660B (en) * | 2020-03-10 | 2022-01-25 | 中国科学院苏州生物医学工程技术研究所 | Centrifugal high-flux micro-droplet preparation chip |
| CN112571718B (en) * | 2020-11-13 | 2023-06-20 | 深圳先进技术研究院 | Preparation method of nested structure of micro-channel array plate and liquid drop generating device |
| CN113025478B (en) * | 2021-02-25 | 2021-09-21 | 中食安泓(广东)健康产业有限公司 | Micro-fluidic device, detection system and detection method for POCT quantitative nucleic acid detection |
| EP4351788A1 (en) | 2021-06-04 | 2024-04-17 | Enumerix, Inc. | Compositions, methods, and systems for single cell barcoding and sequencing |
| CN114029500B (en) * | 2021-11-09 | 2023-01-06 | 南京大学 | Production device and production method of silver nanowires suitable for hundred kilogram level |
| US11834714B2 (en) | 2021-12-20 | 2023-12-05 | Enumerix, Inc. | Detection and digital quantitation of multiple targets |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1362634A1 (en) * | 2001-02-23 | 2003-11-19 | Japan Science and Technology Corporation | Process for producing emulsion and microcapsules and apparatus therefor |
| CN103394380A (en) * | 2013-07-31 | 2013-11-20 | 中国科学院上海微系统与信息技术研究所 | High-flux trace liquid sample distribution device and use method |
| CN103454126A (en) * | 2013-07-20 | 2013-12-18 | 中国科学技术大学 | Adjustable liquid droplet generating device |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104450891B (en) * | 2014-11-17 | 2017-06-06 | 中国科学院微生物研究所 | Digital nucleic acid amplification quantitative analysis method and system based on microlayer model |
-
2015
- 2015-04-03 CN CN201510155219.3A patent/CN104741158B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1362634A1 (en) * | 2001-02-23 | 2003-11-19 | Japan Science and Technology Corporation | Process for producing emulsion and microcapsules and apparatus therefor |
| CN103454126A (en) * | 2013-07-20 | 2013-12-18 | 中国科学技术大学 | Adjustable liquid droplet generating device |
| CN103394380A (en) * | 2013-07-31 | 2013-11-20 | 中国科学院上海微系统与信息技术研究所 | High-flux trace liquid sample distribution device and use method |
Non-Patent Citations (1)
| Title |
|---|
| Alginate bead fabrication and encapsulation of living cells under centrifugally induced artificial gravity conditions;HAEBERLE et al.;《Journal of Microencapsulation》;20080625;第25卷(第4期);268-271 |
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