CN207862346U - A kind of Microfluidic droplet generation chip - Google Patents
A kind of Microfluidic droplet generation chip Download PDFInfo
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- CN207862346U CN207862346U CN201721697460.XU CN201721697460U CN207862346U CN 207862346 U CN207862346 U CN 207862346U CN 201721697460 U CN201721697460 U CN 201721697460U CN 207862346 U CN207862346 U CN 207862346U
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Abstract
The utility model provides a kind of Microfluidic droplet generation chip, including substrate and multiple drop formation units, drop formation unit includes oil storage pool, tank, oil phase runner, water phase runner, drop runner and droplet transfer pipe, substrate includes the first surface and second surface being oppositely arranged, oil storage pool, tank are located on substrate first surface, and oil phase runner, water phase runner and drop runner are embedded in substrate；The opposite end of drop runner is respectively equipped with mixing entrance and drop outlets；Oil phase runner is intersected in one end of water phase runner and mixes entrance, and the other end of oil phase runner and water phase runner is respectively communicated to oil storage pool and tank；Droplet transfer pipe is located on substrate, and drop outlets are connected with the inner cavity of droplet transfer pipe, and droplet transfer pipe has the extension set on second substrate surface, and extension is for connecting drip collector.The flux of analysis sample can be improved in the chip, and the drop of generation can be more fully hereinafter transferred out.
Description
Technical field
The utility model is related to drop micro fluidic chip technical fields more particularly to a kind of Microfluidic droplet to generate chip.
Background technology
Digital pcr (Digital PCR) technology is the third generation after generation regular-PCR, two generation quantitative fluorescent PCRs
Round pcr.Its principle is that the quantitative fluorescent PCR reaction system containing determined nucleic acid molecule is dispersed to ten hundreds of micro-volumes
Unit, each micro-volume are free of or at most include only 1 determined nucleic acid molecule.Each micro-volume is single as an independent reaction
Member, after the completion of amplification, fluorescence signal could be generated by only including the microbody product unit of determined nucleic acid molecule.Detection is each micro- one by one
The fluorescence signal of elementary volume, volume element, it is 1 to have fluorescence signal interpretation, and unstressed configuration signal interpretation is 0, counts and obtains core to be measured in sample
The copy number of acid molecule.
Currently, digital pcr can be divided into microwell plate chip digital PCR and drop digital pcr according to the generating mode of droplet
(Droplet Digital PCR).And drop number round pcr is the Water-In-Oil drop technique based on micro-fluidic chip, it will be every
Part PCR reaction systems are divided into many drops, each drop to be used as an independent PCR reaction member, therefore, number of drops
Amount of droplets that word PCR is provided is more, high sensitivity, test result are more acurrate, referred to as the higher skill of degree of adopting on the market at present
Art.
However, in actual mechanical process, the flux of the analysis sample of drop digital pcr equipment is relatively low, and drop cannot be real
It is now automatic to collect, the requirement of clinically high throughput analysis can not be met.
Utility model content
In view of this, this application provides a kind of Microfluidic droplets to generate chip, which generates chip and includes
Multiple independent drop formation units, can be improved the flux of analysis sample, and the drop of generation can be more fully hereinafter transferred out.
Specifically, this application provides a kind of Microfluidic droplets to generate chip, including substrate and the setting of multiple spacing side by side
Drop formation unit, each drop formation unit includes oil storage pool, tank, oil phase runner, water phase runner, drop stream
Road and droplet transfer pipe, the substrate include the first surface and second surface being oppositely arranged, and the oil storage pool, tank are located at
On the first surface of the substrate, the oil phase runner, water phase runner and drop runner are embedded in the substrate；It is each described
The opposite end of drop runner is respectively equipped with mixing entrance and drop outlets；One end of the oil phase runner and the water phase runner
Be intersected in the mixing entrance, the other end of the oil phase runner and the water phase runner be respectively communicated to the oil storage pool and
The tank；The droplet transfer pipe is set on the substrate, the inner cavity phase of the drop outlets and the droplet transfer pipe
Connection, the droplet transfer pipe also have the extension of the second surface set on the substrate, and the outlet of the extension is used for
Connect drip collector.
Wherein, the first surface of the substrate is additionally provided with the first trepanning, first trepanning and the droplet transfer pipe
Inner cavity is connected.
Wherein, the substrate includes the first substrate and the second substrate to fit, and the oil storage pool, tank are located at described
First substrate deviates from the surface of second substrate, and the first surface is the table that first substrate deviates from second substrate
Face；The oil phase runner, water phase runner and drop runner are located at second substrate towards the surface of first substrate；It is described
First through hole and the second through-hole are offered on first substrate respectively, the first through hole is located at the oil storage pool and the oil phase stream
Between road, for the oil storage pool to be connected with the oil phase runner；Second through-hole be located at the tank with it is described
Between water phase runner, for the tank to be connected with the water phase runner；
The droplet transfer pipe is arranged on second substrate, and the extension is convexly equipped in second substrate and deviates from
The one side of first substrate；The second surface is the surface that second substrate deviates from first substrate；Described first
Trepanning is located on first substrate.
Wherein, the droplet transfer pipe further includes first pipe, and the first pipe is arranged on the substrate, and part
It is convexly equipped in the first surface of the substrate；It is equipped with buffer stopper in the first pipe, the buffer stopper is by the first pipe
Inner cavity is divided into the first cavity, the second cavity and the channel being connected between first cavity and second cavity；
First cavity is connected with the drop outlets, the extension of second cavity and the droplet transfer pipe
It is connected, so that the drop generated followed by first cavity, the channel, second cavity and passes through the extension
The outlet in portion is transferred out.
Wherein, the opposite end of the buffer stopper is respectively connected to the inner wall of the first pipe, the first pipe tool
There are the first end face of the first surface far from the substrate, the buffer stopper that there is the second end face towards the first end face,
The second end face inside contracts in the first pipe.
Wherein, first cavity includes the first open end and the second open end being oppositely arranged, the second cavity packet
Include the third open end and the 4th open end being oppositely arranged, at second open end, the drop outlets with it is described
First cavity is connected；4th open end is connected with the extension；First open end, the equal court in third open end
To the first end face, and the distance of first open end away from the first end face is less than the third open end away from described the
The distance of end face.
Wherein, the substrate includes the first substrate and the second substrate, and the oil storage pool, tank are located at first substrate
Away from the surface of second substrate, the first surface is the surface that first substrate deviates from second substrate；It is described
Oil phase runner, water phase runner and drop runner are located at first substrate towards the surface of second substrate；First base
On piece distinguishes first through hole and the second through-hole, the first through hole are used between the oil storage pool and the oil phase runner
The oil storage pool is connected with the oil phase runner；Second through-hole be located at the tank and the water phase runner it
Between, for the tank to be connected with the water phase runner；
The droplet transfer pipe is arranged on first substrate, and the extension is convexly equipped in the first substrate direction
The surface of second substrate；The first pipe part is convexly equipped in the surface that first substrate deviates from second substrate,
The first surface and two apparent surfaces that second surface is respectively first substrate；The buffer stopper also have with it is described
The third end face that second end face is oppositely arranged, the third end face are bonded with second substrate surface；
Second substrate fits with first substrate, and closes the oil phase runner, water phase runner and drop stream
Road and the first through hole and the second through-hole are close to the open end of bottom plate and the second open end of first cavity.
Wherein, the substrate includes the upper substrate, middle substrate and bottom plate being bonded successively, and the oil storage pool and tank are located at
The upper substrate deviates from the surface of the middle substrate, and the first pipe is located on the upper substrate, and is partly convexly equipped in described
Upper substrate deviates from the surface of the middle substrate；The buffer stopper also has the third end face being oppositely arranged with the second end face,
The third end face is bonded with the middle substrate surface；The extension is convexly equipped in the upper substrate towards the table of the middle substrate
Face, the first surface and two apparent surfaces that second surface is respectively the upper substrate；
The oil phase runner, water phase runner and drop runner are located at the middle substrate towards the surface of the bottom plate；It is described
It is respectively equipped with fourth hole corresponding with the inner cavity of the oil storage pool and fifth hole on upper substrate, middle substrate, the described 4th
Through-hole and fifth hole are for the oil storage pool to be connected with the oil phase runner；It is set respectively on the upper substrate, middle substrate
There are the 6th through-hole corresponding with the inner cavity of the tank and the 7th through-hole, the 6th through-hole and the 7th through-hole to be used for institute
Tank is stated with the water phase runner to be connected；It is logical that the corresponding with first cavity the 8th is additionally provided on the middle substrate
Hole, the 8th through-hole is for first cavity to be connected with the drop runner；
The bottom plate fits with the middle substrate, and close the oil phase runner, water phase runner and drop runner and
The fifth hole, the 7th through-hole and the 8th through-hole are close to an open end of bottom plate.
Wherein, the internal diameter of first cavity is less than the internal diameter of second cavity；The internal diameter of second cavity is equal to
The internal diameter of the extension.
Wherein, along the entrance of the oil storage pool to the direction of the mixing entrance, the runner internal diameter of the oil phase runner exists
It is gradually reduced close to the mixing inlet；Entrance along the tank to the direction of the mixing entrance, draw by the water phase
The runner internal diameter of air stream enter runner is gradually reduced close to the mixing entrance.
Wherein, the width range of the water phase runner is 10-200 μm；The width range of the oil phase runner is 20-200 μ
m；The width of the drop runner is 30-200 μm；The depth bounds of the oil phase runner, water phase runner and drop runner are
10-100μm。
Wherein, the intracavity diameter of the oil storage pool is 0.2-0.6mm, and the height of the oil storage pool is 2-6mm；The water storage
The intracavity diameter in pond is 0.2-0.6mm, and the height of the oil storage pool is 2-6mm.
The Microfluidic droplet provided by the present application generates in chip, includes multiple drop formation lists arranged side by side
Member can simultaneously handle multiple samples, generate multiple independent drops respectively, meet the demand of high throughput analysis,
In addition, the drop generated can be fully transferred to by corresponding droplet transfer pipe in corresponding drip collector, can avoid
Cross contamination between drop realizes the automatic collection of drop.
The advantages of the application, will partly illustrate in the following description, and a part is apparent according to specification
, or can be known by the implementation of the embodiment of the present application.
Description of the drawings
More clearly to illustrate the construction feature and effect of the application, come below in conjunction with the accompanying drawings with specific embodiment to its into
Row is described in detail.
Fig. 1 is the perspective view that Microfluidic droplet generates chip in one embodiment of the application；
Fig. 2 is the flow passage structure schematic diagram of Fig. 1 chips；
Fig. 3 is the vertical view shaft side figure of Fig. 1 chips；
Fig. 4 is another shaft side figure of Fig. 1 chips；
Fig. 5 is the exploded view (depression angle) of Fig. 1 chips；
Fig. 6 is another exploded view (looking up angle) of Fig. 1 chips；
Fig. 7 be Fig. 1 chips along the directions A-A sectional view (along also cross same drop formation unit oil storage pool and
The directions AA of the symmetry axis of tank)；
Fig. 8 is the perspective view that Microfluidic droplet generates chip in another embodiment of the application；
Fig. 9 is the vertical view shaft side figure of Fig. 8 chips；
Figure 10 is another shaft side figure of Fig. 8 chips；
Figure 11 is the amplification schematic top plan view of first pipe 18 in Fig. 9；
Figure 12 is the sectional view of Fig. 8 chips (along the oil storage pool and tank pair also cross same drop formation unit
Claim the direction of axis)；
Figure 13 is the exploded view (depression angle) of Fig. 8 chips；
Figure 14 is that first substrate 30 of Figure 13 chips looks up shaft side figure；
Figure 15 is the exploded view that Microfluidic droplet generates chip in the another embodiment of the application；
Figure 16 is that the upper substrate 50 of Figure 15 chips and subtegulum 60 look up shaft side figure；
Figure 17 is the sectional view of Figure 15 chips (along the oil storage pool and tank also cross same drop formation unit
The direction of symmetry axis)；
Figure 18 is to generate the drop figure that chip generates using Microfluidic droplet provided by the embodiments of the present application.
Main appended drawing reference is as follows：Substrate 1, the first surface 101 of substrate, second surface 102, drop formation unit 100,
Oil storage pool 11, tank 12, oil phase runner 13, water phase runner 14, drop runner 15, droplet transfer pipe 16, extension 17, first
Pipeline 18, buffer stopper 19, the first cavity 80, the second cavity 90, channel 70, the first end face 181 of first pipe 18, buffer stopper 19
Second end face 191.
Specific implementation mode
Below in conjunction with the embodiment of the present application and respective drawings, technical solutions in the embodiments of the present application carry out it is clear,
It is fully described by.Obviously, described embodiment is a part of the embodiment of the application, rather than whole embodiments.Based on this
Embodiment in application, those of ordinary skill in the art are obtained every other without making creative work
Embodiment should all belong to the range of the application protection.
Also referring to Fig. 1-Fig. 4, one embodiment of the application provides a kind of Microfluidic droplet generation chip, is used for drop
Generation, be particularly suitable for the generation of water-in-oil drop.
Specifically, it includes the multiple independences of substrate 1 and spacing side by side setting on substrate 1 which, which generates chip,
Drop formation unit 100, each drop formation unit 100 include oil storage pool 11, tank 12, oil phase runner 13, aqueous phase stream
Road 14, drop runner 15.Here, the number of drop formation unit 100 can be 8-16 etc., and number can simultaneously be located according to required
The sample size of reason designs.The oil storage pool 11, tank 12 all have the cavity of certain volume, and oil storage pool 11 is to load
The oil phase reagent of certain volume, oil phase runner 13 are the flow channels of oil phase reagent.Tank 12 is to load certain volume
Water phase sample, water phase runner 14 is the flow channel of water phase sample.Water phase sample includes but not limited to PCR reaction solution (polymerization
Enzyme chain reaction liquid), for example, mixed liquor of DNA target fragments, PCR primer, PCR reaction enzymes and substrate.The formation of drop
Journey hereafter will be continuing on.
The substrate 1 includes the first surface 101 being oppositely arranged and second surface 102, the oil storage pool 11, tank 12
It is located on the first surface 101 of the substrate, the oil phase runner 13, water phase runner 14 and drop runner 15 are embedded in the base
In plate 1；The opposite end of each drop runner 15 is respectively equipped with mixing entrance 151 and drop outlets 152；The oil phase stream
Road 13 and one end of the water phase runner 14, which are intersected in, described mixes entrance 151, the other end connection of the oil phase runner 15
To the oil storage pool 11, the other end of the water phase runner 14 is connected to the tank 12.Drop formation unit 100 further includes
Droplet transfer pipe 16, droplet transfer pipe 16 are set on substrate 1, the inner cavity of the drop outlets 152 and the droplet transfer pipe 16
It is connected, there is the droplet transfer pipe 16 extension 17 set on the second substrate surface 102, the extension 17 to have
One outlet, the outlet is for connecting drip collector (not shown).Wherein, the accessible drip collector of extension 17 includes
But eight unions of PCR are not limited to, can also be test tube, reagent bottle etc..Optionally, the extension 17 protrudes the second table of substrate
The length in face 102 is 1-3mm, can be convenient for preferably connecting drip collector in this way.
Oil phase reagent is added through oil storage pool 11 and is flowed in oil phase runner 13, and water phase sample is added simultaneously through tank 12
It is flowed in water phase runner 14, oil phase reagent is intersected at the mixing entrance 151 of drop runner 15 with water phase sample, mixed
(15a in such as Fig. 2), water phase sample generate the liquid of many water-in-oil types under surface tension, the shear action of oil phase reagent
Drop, is equivalent to form multiple micro- reative cells.The drop of generation is transferred out after flowing into drop transfer pipe 16.
To make every part of water phase sample produce the drop of preset quantity (such as 20-100 ten thousand), optionally, oil phase reagent exists
Flow velocity in the oil phase runner 13 is 1-100 μ L/min, preferably 5-50 μ L/min.Water phase sample is in the water phase runner 14
In flow velocity be 1-100 μ L/min, preferably 5-50 μ L/min.The control of flow velocity in each runner, can be by from corresponding oil storage
Gas pressure is passed through to control in pond 11, tank 12.In addition, may be implemented by the pressure difference for adjusting water phase and oil phase reagent
Adjust the size of drop.
The size of each runner is closely related in the size and chip of the drop.It is default to make every part of water phase sample produce
The drop of quantity (such as 20-100 ten thousand), optionally, the depth (or height) of the oil phase runner 13 is 10-100 μm.It is described
The depth of water phase runner 14 is 10-100 μm.The depth of the drop runner 15 is 10-100 μm.The width of the water phase runner 14
Ranging from 10-200 μm of degree；The width range of the oil phase runner 13 is 20-200 μm；The width range of the drop runner 15
It is 30-200 μm.
Further, referring to Fig. 2, the entrance along the oil storage pool 11 is to the direction of the mixing entrance 151, the oil phase
The runner internal diameter of runner 13 is gradually reduced at the mixing entrance 151；Entrance along the tank 12 is mixed to described
It is incorporated into the direction of mouth 151, the runner internal diameter of the water phase runner 14 is gradually reduced at the mixing entrance 151.In this way
Under capillary action, water phase sample will be carried out relatively effective " shearing " by mixing the oil phase reagent at entrance 151 so that water phase sample
One layer of oil phase reagent is wrapped up in sheet.Ultimately form multiple uniform, stable, independent drops of microenvironment.
Optionally, at the mixing entrance 151, most narrow runner (including oil phase runner 13, water phase runner 14,
Drop runner 15) width be 10-100 μm, further preferably 10-50 μm.
To make every part of water phase sample produce the drop of preset quantity (such as 20-100 ten thousand), optionally, the oil storage pool
11 intracavity diameter is 0.2-0.6mm, and the height of the oil storage pool 11 is 2-6mm.The intracavity diameter of the tank 13 is
The height of 0.2-0.6mm, the tank are 2-6mm.
Optionally, along the first surface 101 of the substrate to the direction of second surface 102, the oil storage pool 11 with it is described
The cavity internal diameter of tank 12 is gradually reduced.
In the present embodiment, the runner in drop formation unit 100 is " folder stream aggregation " formula structure.Oil phase runner 13 is close
The exit of oil storage pool 11 branches into two runners, this 2 runners converge at the friendship of oil phase runner 13 and water phase runner 14
At remittance, i.e., at the mixing entrance 151.The shape of each runner and runner mouth is not limited to shown in Fig. 2, can also be T-type,
The drop formations flow passage structure such as Y types, cross type.Here it is no longer illustrated one by one.And section of oil storage pool 11, tank 12
Face is also not necessarily limited to for circle, to be designed to other figures according to actual needs.
In the present embodiment, about the 16 droplet transfer pipe is got through.Specifically, the first surface of the substrate 1 is also
Equipped with the first trepanning 103, first trepanning 103 is correspondingly arranged with about the 16 droplet transfer pipe, and described first
Trepanning 103 is connected (internal structure can be referring specifically to Fig. 7) with the inner cavity of the droplet transfer pipe 16.Such structure design,
It can be passed through a certain amount of gas when the droplet of generation is excessively small from first trepanning 103, make droplet swimmingly from described
Droplet transfer pipe 16 is transferred out, be not because drop than oil it is light to be gathered in the upper surface of channel outlet due to hang over the liquid
It drips in transfer pipe 106.Further, the first trepanning 103 and the coaxial of droplet transfer pipe 16 are arranged, and the two size phase
Together.
Its composition is introduced from the preparation angle of said chip below, also referring to chip as shown in Figure 5 and Figure 6 point
Xie Tu and whole chip sectional view shown in Fig. 7.The substrate 1 includes the first substrate 10 and the second substrate 20 to fit,
The oil storage pool 11,12 projection of tank are on the surface that first substrate 10 deviates from second substrate 20, the oil phase
Runner 13, water phase runner 14 and drop runner 15 it is recessed in second substrate 20 towards the surface of first substrate 10.On
The first surface 101 for the substrate that text refers to refers herein to the surface that first substrate 10 deviates from second substrate 20.
First through hole 110 and the second through-hole 120 are offered on first substrate 10 respectively.The first through hole 110 with
The inner cavity of the oil storage pool 11 is connected, and first through hole 110 is also connected with one end of the oil phase runner 13, in the first substrate
After 10 are bonded with the second about 20 substrate, the first through hole 110 is located in the oil storage pool 11 and the oil phase runner 13
Between, first through hole 110 is for the oil storage pool 11 to be connected with the oil phase runner 13.Second through-hole 120 and institute
The inner cavity for stating tank 12 is connected, and the second through-hole 120 is also connected with one end of the water phase runner 14, in the first substrate 10
After being bonded with the second about 20 substrate, second through-hole 120 be located in the tank 12 and the water phase runner 14 it
Between, the second through-hole 120 is for the tank 12 to be connected with the water phase runner 14.Further, the first through hole
110 are correspondingly arranged with the coaxial of the oil storage pool 11, and the size of the first through hole 110 and the oil storage pool 11 is interior
Chamber size is equal；Second through-hole 120 and the coaxial of the tank 12 are correspondingly arranged, and second through-hole 120
Size and the inner cavity of the tank 12 it is equal sized.
The droplet transfer pipe 16 is arranged on second substrate 20, the drop outlets of the drop runner 15 with it is described
The inner cavity of droplet transfer pipe 16 is connected, and the extension 17 is convexly equipped in second substrate 20 and deviates from first substrate
10 one side.And the second surface 102 of the above-mentioned substrate referred to herein refers to second substrate 20 and deviates from first base
The surface of piece 10；Above-mentioned the first trepanning 103 referred to is located on first substrate 10.
Each structure (such as oil storage pool 11, tank 12) on first substrate 10 can be added by way of injection molding
Work；Each structure (droplet transfer pipe 16) on second substrate 20 can also be processed by way of injection molding.In addition, right
Laser engraving method or circuit board engraving may be used in each runner (oil phase runner, water phase runner and drop runner) of said chip
Machine (mainly using rotary milling tools) processes.
Mode by the fitting sealing-in of first substrate, 10 and second substrate 20 is UV ozone low-temperature sealing.By institute
It states the first substrate 10 and after the second substrate 20 carries out fitting sealing-in, oil phase runner 13, the water phase runner in the second substrate 20 can be made
14 and drop runner 15 by first substrate 10 closing form closed flow.Meanwhile also by the first through hole 110 close to oil
The open end of phase runner 13, second through-hole 120 are closed close to the open end of water phase runner 14, so also indirectly
Realize the closing of oil storage pool 11 and 12 bottom of tank.
Optionally, in the present embodiment, the area equation of second substrate, 20 and first substrate 10.Optionally, described
The thickness of one substrate 10 is 1-4mm；The thickness of second substrate 20 is 1-4mm.Optionally, the first substrate 10, the second substrate
20 material can be glass or hard high molecular polymer (such as PMMA, PC, COC, PS etc.).
Preferably, after carrying out being bonded sealing-in with second substrate 20 by first substrate 10, further include：To institute
Oil phase runner 13, water phase runner 14, drop runner 15 is stated to be surface-treated.The surface treatment includes hydrophilicity-imparting treatment or dredges
Hydration process.It is to carry out silicic acid anhydride, and be then progress for oil phase runner 13 and drop runner 15 for water phase runner 14
Hydrophilicity-imparting treatment.Specifically, oxygen plasma can be used to handle in the hydrophilicity-imparting treatment, but not limited to this.It is described hydrophobic
Hydrophobic silanization reagent (such as fluoroalkyl silanes) can be used to carry out in change processing, but not limited to this.
Next it introduces the Microfluidic droplet that another embodiment of the application provides and generates chip, also referring to Fig. 8-figure
12, it includes the multiple independent drop formation lists of substrate 1 and spacing side by side setting on substrate 1 which, which generates chip,
Member, each drop formation unit include oil storage pool 11, tank 12, oil phase runner 13, water phase runner 14, drop runner 15.Institute
It includes that the first surface 101 being oppositely arranged and second surface 102, the oil storage pool 11, tank 12 are located at the base to state substrate 1
On the first surface 101 of plate, the oil phase runner 13, water phase runner 14 and drop runner 15 are embedded in the substrate 1；Each
The opposite end of the drop runner 15 is respectively equipped with mixing entrance 151 and drop outlets 152；The oil phase runner 13 with it is described
One end of water phase runner 14 is intersected in the mixing entrance 151, and the other end of the oil phase runner 15 is connected to the oil storage
The other end in pond 11, the water phase runner 14 is connected to the tank 12.Drop formation unit further includes droplet transfer pipe
16 ', droplet transfer pipe 16 ' is located on substrate 1, and the drop outlets 152 are connected with the inner cavity of the droplet transfer pipe 16 ',
The droplet transfer pipe 16 ' includes the extension 17 for the second surface 102 for being convexly equipped in the substrate, the outlet of the extension 17
For connecting drip collector (not shown).The construction and structure of each component of the above have carried out in Fig. 1-Fig. 7 in detail
Thin to introduce, which is not described herein again.
The difference is that, the drop in the present embodiment turns with the generation chip of Microfluidic droplet shown in Fig. 1-Fig. 7
It further includes first pipe 18 to move pipe 16 ', and the first pipe 18 is arranged on the substrate 1, and part is convexly equipped in the substrate
First surface 101.Referring to Figure 10-Figure 12, it is equipped with buffer stopper 19 in the first pipe 18, the buffer stopper 19 is by described the
The inner cavity of one pipeline 18 is divided into the first cavity 80, the second cavity 90 and connection in first cavity 80 and second cavity
Channel 70 between 90.Channel 70 is located at the top of the first cavity 80 and second cavity 90.First cavity 80 and institute
It states drop outlets 152 to be connected, second cavity 90 is connected with the extension 17 of the droplet transfer pipe 16, generates in this way
Drop from drop runner 15 to flow into the first cavity after 80s, can be followed by first cavity 80, the channel 70, the
Two cavitys 90 are simultaneously transferred out by the outlet of the extension 17.In addition, the design of the first pipe 18 of above structure, can subtract
Impact of the drop generated less to 16 inner wall of droplet transfer pipe, improves the service life of chip.
Further, the opposite end of the buffer stopper 19 is respectively connected to the inner wall of the first pipe 18；Described
There is one pipeline 18 first end face 181 of the first surface 101 far from the substrate, the buffer stopper 19 to have towards described the
The second end face 191 of end face 181, the second end face 181 inside contract in the first pipe 18.It is apparent that described second
Distance of the end face 191 away from second substrate surface 102 is less than distance of the first end face 181 away from second substrate surface 102.This
Sample, drop are the interior intracavitary progress in entire first pipe 18 reaching the flowing before extending step 17.
Further, first cavity 80 includes the first open end 801 (figure does not put on label) being oppositely arranged and the
Two open ends 802, at close second open end 802, the drop outlets 152 of the drop runner 15 and first chamber
Body 80 is connected.Second cavity 90 includes that (figure is to put on for the third open end 901 that is oppositely arranged and the 4th open end 902
Label), the 4th open end 902 is connected with the extension 17.First open end 801, third open end 901 are equal
Towards the first end face 181, and first open end, 801 distance away from the first end face 181 is opened less than the third
Distance of the mouth end 901 away from the first end face 181.That is, the second end face 191 of buffer stopper 19 is not parallel to substrate surface, from
For first cavity 80 to the direction of the second cavity 90, the buffer stopper 19 tilts down setting, the drop generated can be convenient for borrow in this way
Gravity is helped swimmingly to flow to the second cavity 90 from the first cavity 80 via the channel 70 above the buffer stopper 19.
Optionally, the internal diameter of first cavity 80 is less than the internal diameter of second cavity 90.Second cavity 90 leans on
Internal diameter at nearly extension 17 is equal to the internal diameter of the extension 17.It can be convenient for the drop generated in the first cavity 80 in this way
Liquid level is high, and drop less stops in the first cavity 80, flows to droplet transfer pipe via the second cavity 90 quickly
16 extension.
Its decomposition texture composition is introduced from the preparation angle of Fig. 8-chips illustrated in fig. 12 below, also referring to upper
State Fig. 8-Figure 12 and Figure 13-14 figures.The substrate 1 includes the first substrate 30 and the second substrate 40, the oil storage pool 11, storage
Pond 12 is located at the surface that first substrate 30 deviates from second substrate 40, the oil phase runner 13,14 and of water phase runner
Drop runner 15 it is recessed in first substrate 30 towards the surface of second substrate 40；First table of substrate mentioned above
Face 101 herein refers to the surface that first substrate 30 deviates from second substrate 40.
Offer first through hole 310 and the second through-hole 320 on first substrate 30 respectively, the first through hole 310 with
The inner cavity of the oil storage pool 11 is connected, and first through hole 310 is also connected with one end of the oil phase runner 13, in the first substrate
After 30 are bonded with the second about 40 substrate, the first through hole 310 is located at the lower section of 11 inner cavity of oil storage pool, first through hole 310
Between the oil storage pool 11 and the oil phase runner 13, first through hole 310 is used for the oil storage pool 11 and the oil phase
Runner 13 is connected.Second through-hole 320 is connected with the inner cavity of the tank 12, the second through-hole 120 also with the water
One end of phase runner 14 is connected, and after the first substrate 30 is bonded with the second about 40 substrate, second through-hole 320 is just
Lower section positioned at 12 inner cavity of tank, the second through-hole 320 are located between the tank 12 and the water phase runner 14, and second
Through-hole 320 is for the tank 12 to be connected with the water phase runner 14.
The droplet transfer pipe 16 is arranged on first substrate 30, and first pipe 18 is also disposed at the first substrate 30
On, and 18 part of first pipe is convexly equipped in the surface that first substrate 30 deviates from second substrate 40, extension 17 is convex
Set on first substrate 30 towards the surface of second substrate 40；The first surface 101 and second of the above-mentioned substrate referred to
Surface 102 is respectively two apparent surfaces of first substrate 30.The buffer stopper 19 also has and the second end face 191
The third end face 192 being oppositely arranged, the third end face 192 are bonded with the upper surface of second substrate 40.
After second substrate 40 and first substrate 30 are fitted, the oil phase runner 13, water phase can be closed
Runner 14 and drop runner 15 and the first through hole 310 are close to the open end of oil phase runner 13, second through-hole 320
Close to the open end of water phase runner 14 and the second open end 802 of first cavity 80.Also realize oil storage pool indirectly in this way
11 with the closing of 12 bottom of tank.
It should be noted that in this embodiment, second substrate 40 and the area of the first substrate 30 differ, and first
The area of substrate 30 is more than the area of the second substrate 40, and there is no closed the outlet of extension 17 for the second substrate 40.The
Two substrates 40 are a complete tablet, do not carry out any processing.Optionally, the thickness of second substrate 40 is 1-4mm, into one
Step is chosen as 0.5-2mm.The thickness of first substrate 30 is 1-4mm.The processing side of each structure on first substrate 30
The sealing-in mode of formula, the first substrate 30 and the second substrate 40 is same as above, and which is not described herein again.Optionally, first substrate
The first pipe 18 and extension 17 of droplet transfer pipe 16 on 30 can be integrally formed.
Be described below with the decomposition texture of the slightly different another chip of Figure 12-chips illustrated in fig. 14, please together
5- Figure 17 refering to fig. 1.
The substrate that the Microfluidic droplet generates chip includes the upper substrate 50, middle substrate 60 and bottom plate 200 being bonded successively.
Wherein, each structure on upper substrate 50 (including extension 17, first pipe 18 etc.) is complete with the structure of above-mentioned first substrate 30
Equally, it is not further described herein.Bottom plate 200 is also a complete tablet, does not carry out any processing.In addition, the buffer stopper
Third end face 192 be to be bonded with the upper surface of the middle substrate.
The difference is that the oil phase runner 13, water phase runner 14 and drop runner 15 are recessed in the middle substrate
60 towards the surface of the bottom plate 200；The inner cavity phase with the oil storage pool 11 is respectively equipped on the upper substrate 50, middle substrate 60
Corresponding fourth hole 501 and fifth hole 601, wherein the fourth hole 501 and fifth hole 601 are used for the oil storage
Pond 11 is connected with the oil phase runner 13.Be respectively equipped on the upper substrate 50, middle substrate 60 in the tank 12
Corresponding 6th through-hole 502 of chamber and the 7th through-hole 602, the 6th through-hole 502 and the 7th through-hole 602 are used for the storage
Pond 12 is connected with the water phase runner 14.Corresponding with first cavity 80 is additionally provided on the middle substrate 60
Eight through-holes 603, the 8th through-hole 603 is for first cavity 80 to be connected with the drop runner 15.Here
" corresponding " setting refers to coaxial arrangement, for example, the fourth hole 501 and fifth hole 601 and the oil storage pool 11
Inner cavity be coaxially to be arranged up and down, it is preferable that the size of fourth hole 501 and fifth hole 601 with the oil storage pool
11 inner cavity is equal sized.
After the bottom plate 200 and the middle substrate 60 are fitted, the oil phase runner 13, water phase runner 14 can be closed
With the drop runner 15 and fifth hole 601, the 7th through-hole 602 and the 8th through-hole 603 close to bottom plate 200 an opening
End.Also realize the closing of oil storage pool 11 and 12 bottom of tank indirectly in this way.
In such cases, the area of the upper substrate 50 is more than the middle substrate 60, more than the area of bottom plate 200, and in
Substrate 60, bottom plate 200 are not closed the outlet of extension 17 on upper substrate 50.Optionally, 60 He of middle substrate
The area of bottom plate 200 is identical.
Optionally, the thickness of the upper substrate 50 is 1-4mm；The thickness of the middle substrate 60 is 1-4mm；The bottom plate
200 thickness is 0.5-2mm.
It should be noted that the Microfluidic droplet that each decomposition texture assembling of Figure 15-Figure 17 chips obtains later is given birth to
At chip, overall structure and drop micro-fluidic chip shown in Fig. 8-Figure 12 are extremely similar.
When generating the generation of chip progress drop using Microfluidic droplet shown in any figures of the application Fig. 1-Figure 17, gained
The homogeneity of drop is higher (referring to Figure 18), can make CV (coefficient of variation)≤5%.The size of drop can reach 50-100 μm.This
Outside, the 99% of the drop of generation is transferred away.
It should be noted that according to the above description the announcement of book and with illustrate, the application those skilled in the art also
The above embodiment can be changed and be changed.Therefore, the application is not limited to specific reality disclosed and described above
Mode is applied, some equivalent modifications and change to the application should also be as within the protection domain of claims hereof.This
Outside, although having used some specific terms in this specification, these terms are merely for convenience of description, not to the application
Constitute any restrictions.
Claims (10)
1. a kind of Microfluidic droplet generates chip, which is characterized in that the drop formation being arranged including substrate and multiple spacing side by side
Unit, the drop formation unit include oil storage pool, tank, oil phase runner, water phase runner, drop runner and droplet transfer
Pipe, the substrate include the first surface and second surface being oppositely arranged, and the oil storage pool, tank are located at the of the substrate
On one surface, the oil phase runner, water phase runner and drop runner are embedded in the substrate；Opposite the two of the drop runner
End is respectively equipped with mixing entrance and drop outlets；The oil phase runner is intersected in described mix with one end of the water phase runner
The other end of entrance, the oil phase runner and the water phase runner is respectively communicated to the oil storage pool and the tank；It is described
Droplet transfer pipe is set on the substrate, and the drop outlets are connected with the inner cavity of the droplet transfer pipe, and the drop turns
The extension for the second surface that pipe has set on the substrate is moved, the outlet of the extension is for connecting drip collector.
2. Microfluidic droplet according to claim 1 generates chip, which is characterized in that the first surface of the substrate is also set
There are the first trepanning, first trepanning to be connected with the inner cavity of the droplet transfer pipe.
3. Microfluidic droplet according to claim 2 generates chip, which is characterized in that the substrate includes the to fit
One substrate and the second substrate, the oil storage pool, tank are located at the surface that first substrate deviates from second substrate, described
First surface is the surface that first substrate deviates from second substrate；The oil phase runner, water phase runner and drop runner
Second substrate is located at towards the surface of first substrate；First through hole and second are offered respectively on first substrate
Through-hole, the first through hole are used between the oil storage pool and the oil phase runner by the oil storage pool and the oil phase
Runner is connected；Second through-hole is used between the tank and the water phase runner by the tank and institute
Water phase runner is stated to be connected；
The droplet transfer pipe is arranged on second substrate, and the extension is convexly equipped in second substrate away from described
The one side of first substrate；The second surface is the surface that second substrate deviates from first substrate；First trepanning
It is located on first substrate.
4. Microfluidic droplet according to claim 1 generates chip, which is characterized in that the droplet transfer pipe further includes the
One pipeline, the first pipe setting on the substrate, and are partly convexly equipped in the first surface of the substrate；First pipe
Buffer stopper is equipped in road, the inner cavity of the first pipe is divided into the first cavity, the second cavity and connection and existed by the buffer stopper
Channel between first cavity and second cavity；
First cavity is connected with the drop outlets, and second cavity is connected with the extension of the droplet transfer pipe
It is logical, so that the drop generated followed by first cavity, the channel, the second cavity and passes through the outlet of the extension
It is transferred out.
5. Microfluidic droplet according to claim 4 generates chip, which is characterized in that the opposite end of the buffer stopper point
It is not connected to the inner wall of the first pipe；The first pipe has the first end face of the first surface far from the substrate,
There is the buffer stopper second end face towards the first end face, the second end face to inside contract in the first pipe；
First cavity includes the first open end and the second open end being oppositely arranged, and second cavity includes being oppositely arranged
Third open end and the 4th open end, at second open end, the drop outlets and the first cavity phase
Connection；4th open end is connected with the extension；First open end, third open end are towards described first
End face, and the distance of first open end away from the first end face be less than the third open end away from the first end face away from
From.
6. Microfluidic droplet according to claim 5 generates chip, which is characterized in that the substrate include the first substrate and
Second substrate, the oil storage pool, tank are located at the surface that first substrate deviates from second substrate, the first surface
Deviate from the surface of second substrate for first substrate；The oil phase runner, water phase runner and drop runner are located at described
First substrate is towards the surface of second substrate；First through hole and the second through-hole, institute are offered on first substrate respectively
First through hole is stated between the oil storage pool and the oil phase runner, for the oil storage pool to be connected with the oil phase runner
It is logical；Second through-hole is used between the tank and the water phase runner by the tank and the aqueous phase stream
Road is connected；
The droplet transfer pipe is arranged on first substrate, and the extension is convexly equipped in first substrate described in
The surface of second substrate；The first pipe part is convexly equipped in the surface that first substrate deviates from second substrate, described
First surface and two apparent surfaces that second surface is respectively first substrate；The buffer stopper also has and described second
The third end face that end face is oppositely arranged, the third end face are bonded with second substrate surface；
Second substrate fits with first substrate, and closes the oil phase runner, water phase runner and drop runner, with
And the first through hole and second through-hole are close to the open end of bottom plate and the second open end of first cavity.
7. Microfluidic droplet according to claim 5 generates chip, which is characterized in that the substrate includes being bonded successively
Upper substrate, middle substrate and bottom plate, the oil storage pool and tank are located at the surface that the upper substrate deviates from the middle substrate, described
First pipe is located on the upper substrate, and part is convexly equipped in the surface that the upper substrate deviates from the middle substrate；The buffering
Block also has the third end face being oppositely arranged with the second end face, and the third end face is bonded with the middle substrate surface；Institute
It states extension and is convexly equipped in the upper substrate towards the surface of the middle substrate, the first surface is respectively described with second surface
Two apparent surfaces of upper substrate；
The oil phase runner, water phase runner and drop runner are located at the middle substrate towards the surface of the bottom plate；The upper base
Fourth hole corresponding with the inner cavity of the oil storage pool and fifth hole, the fourth hole are respectively equipped on piece, middle substrate
It is used to the oil storage pool with the oil phase runner being connected with fifth hole；Be respectively equipped on the upper substrate, middle substrate with
Corresponding 6th through-hole in inner cavity of the tank and the 7th through-hole, the 6th through-hole and the 7th through-hole are used for the storage
Pond is connected with the water phase runner；The 8th through-hole corresponding with first cavity, institute are additionally provided on the middle substrate
The 8th through-hole is stated for first cavity to be connected with the drop runner；
The bottom plate fits with the middle substrate, and closes the oil phase runner, water phase runner and drop runner and described
Fifth hole, the 7th through-hole and the 8th through-hole are close to the open end of bottom plate.
8. generating chip according to claim 4-7 any one of them Microfluidic droplets, which is characterized in that first cavity
Internal diameter is less than the internal diameter of second cavity；The internal diameter of second cavity is equal to the internal diameter of the extension.
9. generating chip according to claim 1-7 any one of them Microfluidic droplets, which is characterized in that along the oil storage pool
Entrance is gradually reduced to the direction of the mixing entrance, the runner internal diameter of the oil phase runner close to the mixing inlet；
For entrance along the tank to the direction of the mixing entrance, the water phase introduces the runner internal diameter of runner close to described mixed
Mouth is incorporated into be gradually reduced.
10. Microfluidic droplet according to claim 9 generates chip, which is characterized in that the width model of the water phase runner
Enclose is 10-200 μm；The width range of the oil phase runner is 20-200 μm；The width of the drop runner is 30-200 μm；Institute
The depth bounds for stating oil phase runner, water phase runner and drop runner are 10-100 μm；
The intracavity diameter of the oil storage pool is 0.2-0.6mm, and the height of the oil storage pool is 2-6mm；The inner cavity of the tank
The height of a diameter of 0.2-0.6mm, the tank are 2-6mm.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201721697460.XU CN207862346U (en) | 2017-12-07 | 2017-12-07 | A kind of Microfluidic droplet generation chip |
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| CN201721697460.XU CN207862346U (en) | 2017-12-07 | 2017-12-07 | A kind of Microfluidic droplet generation chip |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108004136A (en) * | 2017-12-07 | 2018-05-08 | 深圳市博瑞生物科技有限公司 | A kind of Microfluidic droplet generates chip |
| CN109679842A (en) * | 2019-03-01 | 2019-04-26 | 深圳市博瑞生物科技有限公司 | Micro-fluidic chip |
| CN112657565A (en) * | 2020-12-17 | 2021-04-16 | 京东方科技集团股份有限公司 | Microfluidic channel, control method thereof, microfluidic chip and analysis device |
-
2017
- 2017-12-07 CN CN201721697460.XU patent/CN207862346U/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108004136A (en) * | 2017-12-07 | 2018-05-08 | 深圳市博瑞生物科技有限公司 | A kind of Microfluidic droplet generates chip |
| CN109679842A (en) * | 2019-03-01 | 2019-04-26 | 深圳市博瑞生物科技有限公司 | Micro-fluidic chip |
| WO2020177088A1 (en) * | 2019-03-01 | 2020-09-10 | 深圳市博瑞生物科技有限公司 | Microfluidic chip |
| CN112657565A (en) * | 2020-12-17 | 2021-04-16 | 京东方科技集团股份有限公司 | Microfluidic channel, control method thereof, microfluidic chip and analysis device |
| CN112657565B (en) * | 2020-12-17 | 2022-08-19 | 京东方科技集团股份有限公司 | Microfluidic channel, control method thereof, microfluidic chip and analysis device |
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