CN207899465U - Micro-fluidic chip, drop formation device and microballoon preparation facilities - Google Patents

Abstract

The utility model is related to a kind of micro-fluidic chips, drop formation device and microballoon preparation facilities, wherein, micro-fluidic chip includes matrix (3) and the first flow (1) being located in matrix (3) and second flow channel (2), first flow (1) and second flow channel (2) are crossed to form intersectional region, being sheared phase fluid can flow into from first flow (1), shearing phase fluid can be flowed into from second flow channel (2), to be separated into discrete drop by phase fluid is sheared in intersectional region, the sectional area ranging from 0.1mm of first flow (1) and second flow channel (2)²~1mm².The micro-fluidic chip can increase flow, make to form the raising of the efficiency of drop；Flow velocity can also be reduced, during so that cell is flowed in runner between flow path wall due to caused by friction shearing force reduce, the activity of cell is set to meet the requirements, to increase the efficiency for generating drop on the basis of ensureing cell activity, to meet the needs of 3D biometric prints.

Description

Micro-fluidic chip, drop formation device and microballoon preparation facilities

Technical field

The utility model is related to microsphere preparation technology field more particularly to a kind of micro-fluidic chip, drop formation device and Microballoon preparation facilities.

Background technology

Microballoon has shown that its advantage in numerous applications, includes the structure module simulated for complex organization, is used for Develop co-culture system and the regeneration of three dimensional structure's model.Be loaded with cell microgel re-formed by droplet treatment it is micro- Ball prepares tissue or three dimensional structure for 3D biometric print machines after being cultivated using solidification, is the important original of 3D biometric print machines Material.

When preparing microballoon, it is necessary first to form the drop of separation, there are many kinds of drop technologies of preparing, have emulsification, mixing, The modes such as embedding, extraction, micro- reaction.It is right but due to often being reacted by way of preparing drop Macro Technologies relatively acutely Cell has compared with macrolesion, is not suitable for 3D biometric prints, thus the general liquid prepared using microflow control technique in demand size Drop.

The microgel drop for being loaded with cell at present generally utilizes microflow control technique to synthesize.Microflow control technique is as liquid or gas Body controls more commonly used method, is a kind of to carry out precise manipulation, processing and control to fluid or sample in several nanoscales Technology, the technology for usually sample fluid in fluid channel being operated and being controlled under range scale within 100 μm.Miniflow It is to be based in 100 μm of runners, and used as bioanalysis that control technology, which is used to separation cell liquid, does not propose to limit to cell activity System and requirement.

Micro-fluidic chip microlayer model generating structure is divided into active and passive type, wherein active to pass through electric field force, heat The external force such as energy make liquid stream locally generate energy gradient to be manipulated to microlayer model, include mainly Electrowetting, dielectrophoresis Method, pneumatic process and thermo-capillary method etc., this method can be to the manipulations of single microlayer model.But inevitably active electricity, Magnetic, sound, light, heat etc. can have an adverse effect to cell.Therefore preferably passive in practical applications in order to improve the activity of cell Method manipulates microlayer model by making liquid stream locally generate velocity gradient the design of micro-channel structure, can avoid master Electricity, magnetic, sound, light, heat for being used in dynamic formula microflow control technique etc. can have an adverse effect to cell.

Chip to the research of micro-fluidic chip generally directed to channel size within 100 μm in the prior art, such as 20 μ M, 40 μm, 60 μm, 80 μm, and in terms of the activity for how to ensure to wrap celliferous solution mixture, how to improve yield Or the cutting method etc. for high viscosity raw material, it does not study specifically.

And a bottleneck of 3D biometric prints is raw material (such as the microgel by being loaded with cell formed drop) system Make low yield, it usually needs more biomaterial preparing instruments could meet a 3D biometric print machines job, therefore improve Raw material yield be there is an urgent need to.Micro-assembly robot, or even structure are generated since biometric print raw material can be used in 3D biometric prints Three dimensional structure.But an important premise is that cell activity in biomaterial is needed to be maintained at 60% or more, activity is too low It can cause the tissue printed or three dimensional structure that can not survive.Cell activity in biomaterial is higher, passes through 3D biologies The organ survival printed leads higher.Therefore, it is to compel at present that biological raw material is improved while ensureing cell activity and prepares yield Cut problem to be solved.

Utility model content

The embodiments of the present invention provide a kind of micro-fluidic chip, drop formation device and microballoon preparation facilities, energy It is enough that the efficiency for forming drop is improved on the basis of ensureing to be sheared active needed for cell in phase fluid.

To achieve the above object, the embodiments of the present invention first aspect provides a kind of micro-fluidic chip, including base Body and the first flow being located in described matrix and second flow channel, the first flow and second flow channel intersect and form confluence Domain, being sheared phase fluid can flow into from the first flow, shearing phase fluid can be flowed into from the second flow channel, so as to The phase fluid that is sheared is separated into discrete drop, the sectional area of the first flow and second flow channel by the intersectional region Ranging from 0.1mm²~1mm²。

Further, the first flow is located at the portion size of intersection region upstream and is consistent, or along being cut The flow direction size of cut phase fluid is in increase tendency.

Further, the both sides of the first flow are respectively equipped with a second flow channel, in the intersectional region Form folder stream focus type runner.

Further, the first flow and two second flow channels form criss-cross construction in intersectional region.

Further, each second flow channel is in the L-shaped structure of intersectional region, the transverse part of the L-shaped structure and institute It states first flow connection and perpendicular to first flow, the vertical part of the L-shaped structure is parallel to the first flow.

Further, the distance between the vertical part of the L-shaped structure and the first flow ranging from 0.1mm~20mm.

Further, two second flow channels and the angled setting of the first flow, the second flow channel and first The angle of runner is less than 90 °.

Further, two second flow channels are symmetrical arranged relative to the first flow.

Further, the cross section of the first flow and second flow channel is rectangle, circle or trapezoidal.

Further, the cross section of the first flow and second flow channel is rectangle, the length model of the rectangular cross section It is 0.2mm~0.6mm to enclose for 0.7mm~2mm and/or its width range.

Further, described to be sheared ranging from the 10 of the ratio between phase fluid and the viscosity of the shearing phase fluid:1~30: 1。

Further, the viscosity for being sheared phase fluid is less than 3000cp.

Further, the model for being sheared phase fluid and single channel shearing phase fluid the ratio between flow at the intersectional region Enclose is 1:10~1:20.

Further, it is 100~400 μ L/ that range of flow of the phase fluid at the intersectional region is sheared described in single channel Min, the range of flow of the phase fluid at the intersectional region that be sheared is 10~40 μ L/min.

Further, ranging from 200 μm~400 μm of the diameter dimension of the drop.

Further, the both ends of two second flow channels are passed through the shearing phase fluid by common fluid inlet, Or the both ends of two second flow channels are passed through the shearing phase fluid by independent fluid inlet respectively.

Further, it is equipped with multiple microfluidic cells in described matrix, is all had in each microfluidic cell described Folder stream focus type runner, each microfluidic cell can either simultaneously or alternately work.

Further, the phase fluid that is sheared includes core liquid, covering liquid or curing agent, and the micro-fluidic chip is used for Form core liquid drop, covering liquid drop or curing agent drop.

Further, the core liquid is to wrap celliferous collagen solution, and the shearing phase fluid is oil-based solvent.

To achieve the above object, the embodiments of the present invention second aspect provides a kind of drop formation device, including The micro fluidic device of above-described embodiment.

Further, drop formation device further includes pumping installations, the pumping installations and the first flow and second Runner is connected to, for controlling the speed and flow for being sheared phase fluid and entering the first flow, and shearing phase fluid entrance Speed and flow in the second flow channel.

Further, drop formation device further includes input part, the input part with the first flow and The inlet communication of two runners, the fluid for being used to form drop to the first flow and second flow channel conveying；Or

The drop formation device further includes output block, the output block and the output block, the output section The outlet of part and the first flow and second flow channel, the drop output for that will be formed.

To achieve the above object, it includes upper that the embodiments of the present invention third aspect, which provides a kind of microballoon preparation facilities, State the drop formation device of embodiment.

Based on the above-mentioned technical proposal, the micro-fluidic chip of the utility model one embodiment, by by first flow and The sectional area range of two runners increases to 0.1mm²~1mm², the percent of pass of fluid can be increased, flow increases, makes to form drop Efficiency improve；And channel size increase can also reduce the flow velocity of fluid, during so that cell is flowed in runner with stream Between road wall due to friction and caused by shearing force accordingly reduce, to reduce damage to cell, ensure the activity of cell, and And still has enough shearing forces during control and will be sheared by finely tuning flow and be separated into discrete drop.Therefore originally The micro-fluidic chip of the utility model embodiment can increase the efficiency for generating drop on the basis of ensureing cell activity, with full The demand of sufficient 3D biometric prints.

Description of the drawings

Attached drawing described herein is used to provide a further understanding of the present invention, and is constituted part of this application, The exemplary embodiment of the utility model and the description thereof are used to explain the utility model, does not constitute to the improper of the utility model It limits.In the accompanying drawings：

Fig. 1 is the structural schematic diagram of one embodiment of the utility model micro-fluidic chip；

Fig. 2 is the structural schematic diagram of another embodiment of the utility model micro-fluidic chip；

Fig. 3 is enlarged drawing at the A in Fig. 1 and Fig. 2；

Fig. 4 is the principle schematic that drop is formed by criss-cross construction runner；

Fig. 5 is the principle schematic that drop is formed by T shape runners；

Fig. 6 is dispersed phase solution during the utility model micro-fluidic chip formation microballoon and the body shared by continuous phase solution Fraction schematic diagram；

Fig. 7 is that the utility model micro-fluidic chip forms the big logotype of shearing force being subject to during microballoon；

Fig. 8 is the schematic diagram of the discrete droplets that are obtained by the utility model micro-fluidic chip under the microscope；

Fig. 9 is the droplets size distribution schematic diagram obtained by the utility model micro-fluidic chip.

Reference sign

1, first flow；2, second flow channel；3, matrix；4, container；N, microfluidic cell；11, first fluid import；21、 Second fluid import；12；Drop outlets.

Specific implementation mode

The utility model described further below.In the following paragraphs, the different aspect of embodiment is defined in more detail. The various aspects so limited can be combined with any other one side or many aspects, can not be combined unless explicitly stated otherwise.Especially It is, it is considered to be preferred or advantageous any feature can be considered as preferred or advantageous spy with other one or more Sign combination.

The terms descriptions merely for convenience such as " first " that occurs in the utility model, " second ", with distinguish have it is identical The different building blocks of title are not offered as priority or primary-slave relation.

In the description of the present invention, it should be understood that the noun of locality such as " front, rear, top, and bottom, left and right ", " laterally, Vertically, vertically, it is horizontal " and " pushing up, bottom " etc. indicated by orientation or positional relationship be normally based on orientation or position shown in the drawings Relationship is set, is merely for convenience of describing the present invention and simplifying the description, in the absence of explanation to the contrary, these nouns of locality Do not indicate that and imply that signified device or element must have a particular orientation or with specific azimuth configuration and operation, because This should not be understood as the limitation to scope of protection of the utility model；The noun of locality " inside and outside " refers to the wheel relative to each component itself Wide is inside and outside.

The micro-fluidic chip of the utility model refers to the micro-fluidic chip for having drop formation function, can be used to form preparation Various drops needed for microballoon, for example, forming core liquid drop, covering liquid drop or curing agent drop.

Runner is equipped in micro-fluidic chip, generating the principle of drop is, two kinds of immiscible fluids are passed through miniflow In the runner for controlling chip, one of which fluid is dispersed phase, and as phase fluid is sheared, one other fluid is continuous phase, as Fluid is sheared, by discrete phase fluid partitioning is discrete drop by continuous phase fluid in the region of two kinds of fluid junctions.

Specifically, continuous phase fluid and dispersed phase fluid respectively enter in micro-fluidic chip after corresponding runner, can be not The interface of continuous phase fluid and dispersed phase fluid is formed with the intersection of runner.Dispersed phase fluid is in the promotion of external force and continuous Under the action of phase fluid shearing force with continuous phase fluid synchronize travel forward.When the interfacial tension of interface is not enough to remain continuous When phase fluid is applied to the shearing force of dispersed phase fluid, dispersed phase fluid fracture generates independent by the micro- of continuous phase fluid encirclement Small volume units, that is, drop.

For example, in the case where continuous phase fluid is oil and dispersed phase fluid is water, oil/water circle is formed in grease intersection Face, water phase under the action of the promotion of external force and oil phase shearing force with oil phase synchronize travel forward, when the boundary of oil/water interface When face tension is not enough to that oil phase is maintained to be applied to the shearing force of water phase, water phase fracture generates the independent drop surrounded by oil phase.

It is mentioned in background technology, general micro-fluidic chip generates the less efficient of drop in the prior art, it is difficult to meet The efficient work requirements of 3D biometric print machines, it is therefore desirable to the efficiency that micro-fluidic chip generates drop is improved, it is more to generate Microballoon meets the needs of 3D biometric prints.

In order to solve this problem, inventor notices a kind of structure using cross type runner in the prior art In, first flow is sheared phase fluid for being passed through, such as contains cell solution, and second flow channel is used to be passed through shearing phase fluid, And the position for being located at intersection region upstream in first flow is equipped with nozzle, and main purpose is to increase the flowing for being sheared phase solution Speed, and increase shearing force, so that cell solution is easier to be sheared out, to suitably increase the efficiency that drop generates.

But during practical biological 3D printing, such micro-fluidic chip compares in the improvement of drop yield aspects to be had Limit, is still difficult to meet the needs of biological 3D printing, and finds that the cell in drop may also will appear different degrees of damage Wound, it is difficult to meet the requirement to cell activity in 3D printing.

For this purpose, inventor to above-mentioned micro-fluidic chip equipped with nozzle generate the restricting relation of each parameter during drop into Research is gone.

It is to improve the flow velocity of dispersed phase, and be found through experiments that the advantages of nozzle in existing scheme, if phase will be sheared Further increased with the flow velocity for being sheared phase, can improve the generation frequency of drop, but the raising of flow velocity bring it is direct after Fruit is exactly that shearing force increases substantially.It is demonstrated experimentally that red blood cell can continue that the shearing force of about 150Pa can only be born in (100s). Therefore, for protection cell activity from the point of view of, existing micro-fluidic chip can not improve the yield of drop.And And since there is nozzle the conical outlet of tapered configuration to be easy to strike cone mouth wall surface, also can when cell is flowed out from cone mouth To cell damage, cell activity is caused to decline.

In collateral security drop from the point of view of cell activity, a kind of optional approach be existing channel size (100 μm with Under) directly cancel nozzle on the basis of micro-fluidic chip, then being sheared the flow velocity of phase will reduce, correspondingly shearing force also can It reduces.But since the viscosity for being sheared phase is usually larger so that it is sheared the difficulty increase for being mutually separated into drop, so as to cause Slowing for drop is generated, moreover, the formation efficiency of drop can be reduced by being sheared reduction of phase flow velocity itself also.

On this basis, in order to improve the formation efficiency of drop, it is necessarily required to the flowing for improving shearing phase with being sheared phase On the one hand speed can consume within the unit interval and more be sheared phase fluid, on the other hand shear the increase of phase velocity Also the shearing force that bigger can be provided, reduces the formation difficulty of drop, and the factor of these two aspects is all conducive to improve the generation of drop Efficiency.

But with the increase of two-phase fluid speed, be sheared when phase fluid flows in runner can with runner inner wall it Between generate larger friction, to increase the shearing force that cell is subject to, solution containing cell is in runner in flow process, shearing The activity that can greatly weaken cell is significantly increased in power.

If directly cancelling nozzle on the basis of existing small flow channels, flow velocity can reduce, and shearing force reduces, due to viscous Spend larger, dispersion difficulty increases, and generates microballoon and slows, and dispersed phase flow velocity reduction itself can also reduce yield.Although carrying The speed that height is sheared phase can improve yield, but be sheared and generate friction when mutually being flowed in runner between meeting and flow path wall And shearing force is brought, shearing force is significantly increased the activity that can greatly weaken cell in flow process.It can be seen that directly taking The thinking of nozzle of disappearing still cannot be satisfied on the basis of ensureing cell activity increase drop yield.

For this purpose, inventor is further considered as increasing the mode of channel size, it is contemplated that general in micro-fluidic chip at present All over the channel size used all within 0.5mm × 0.1mm, the research of microflow control technique is also based in the size range, And the variation of channel size can generate the effect of intercoupling with other control parameters in micro-fluidic chip, to generating drop Yield and cell activity impact.Therefore, in celliferous drop formation technical field, because of the not prior art Guiding and enlightenment, it is difficult to expect improving drop production on the basis of ensureing cell activity by way of increasing cross section of fluid channel product Rate.

Above-mentioned analysis is needed, when forming drop by microflow control technique, the size of runner can be to the yield of drop and thin Cytoactive, which generates, directly to be influenced, thus in order to meet the needs of 3D biometric prints, needs to be lived according to the yield and cell of drop Property require to select suitable channel size, and the viscosity of fluid is combined to choose suitable flow velocity, so that each ginseng to intercouple Number is mutually matched, and finally meets yield and the cell activity requirement of drop.This and pass through microflow control technique realize liquid separation chip There is the difference of essence in principle, a series of runner equipped with bifurcateds shunts liquid in liquid separation chip, Ge Geliu The sectional area in road can be directly designed according to the flow of distribution.As it can be seen that since micro-fluidic target is different, pass through micro-fluidic skill The selection of channel size can not use for reference the size of liquid separation chip runner when art forms drop.

For this purpose, inventor is after proposing such improved though, and theory analysis is carried out.After increasing channel size, In same section allow more fluids pass through, can increase fluid within the unit interval by flow.Wherein, it is sheared Phase fluid can increase the consumption of raw material (such as cell solution) by the raising of flow, shear phase fluid carrying by flow Height can increase the shearing force provided cell solution, and the influence factor of these two aspects is capable of the effect of micro-fluidic chip generation drop Rate.

Moreover, if channel size increases, is conducive to adjust shearing phase and is sheared the flow velocity of phase, be embodied in advantageous In reducing two-phase flow velocity, wherein be sheared phase flow velocity reduce after, during flowing in runner cell and runner inner wall it Between also accordingly decreased due to shearing force caused by friction, advantageously ensure that the work before cell is sheared at intersection region Property；After the reduction for shearing phase flow velocity, it can suitably reduce shearing phase fluid and be applied in different runner intersectional regions and be sheared phase The shearing force of flow velocity reduces be sheared phase fluid separation in being brought when predetermined size drop to wrapping celliferous raw material as possible Damage.

Although the flow velocity of shearing phase fluid decreases, the shearing force to being sheared phase fluid offer also accordingly reduces, It is still can have enough shearing forces since shearing phase fluid is increased within the unit interval by the flow in right-angled intersection region Phase fluid will be sheared to separate.It, can also be by micro- when needing the shearing force of bigger if the viscosity for being sheared phase is larger Two-phase flow velocity is adjusted, so that shearing phase fluid is still had sufficiently large shearing force and cell solution is dispersed into drop.By analysis, increase The thinking of micro-fluidic chip channel size can improve the efficiency for generating drop on the basis of ensureing cell activity.

Currently, for the micro-fluidic chip of big runner, how in order to improve drop formation efficiency, and ensure cell activity Convection current track forces cun is designed, two-phase flow velocity is controlled and how to be chosen two-phase viscosity and material etc. it is micro- Fluidics still lacks correlative study.

The utility model is improved micro-fluidic chip in the prior art according to this thinking.It is schematical at one In embodiment, in conjunction with Fig. 1 to Fig. 3, such micro-fluidic chip includes matrix 3 and the first flow 1 and second that are located in matrix 3 Road 2, first flow 1 and second flow channel 2 are interconnected, and first flow 1 and second flow channel 2 intersect and form intersectional region. Being sheared phase fluid can flow into from first flow 1, and shearing phase fluid can be flowed into from second flow channel 2, so as in intersectional region Phase fluid will be sheared and be separated into discrete drop, the sectional area ranging from 0.1mm of first flow 1 and second flow channel 2²~1mm²。 Preferably, sectional area can select 0.1mm²、0.2mm²、0.3mm²、0.4mm²、0.5mm²、0.6mm²、0.7mm²、0.8mm²、 0.9mm²、1mm²Deng.

Wherein, the second flow channel 2 being connected to specific first flow 1 can be one or more, and 1 side of first flow is every One section of independent part for flowing into shearing phase fluid all may be defined as a second flow channel 2.

Preferably, such as Fig. 1 and Fig. 2, the cross section of first flow 1 and second flow channel 2 is rectangle.The runner of rectangular section has Standby following advantage：

(1) facilitate runner processing in matrix 3, size is easily guaranteed that, can reduce the manufacture difficulty of micro-fluidic chip；

(2) channel size, which is easily guaranteed that, can more accurately ensure micro-fluidic parameters, such as accurately control stream Flow velocity of the body at intersection region；

(3) resistance being subject to during fluid flows in runner is smaller, is conducive to carry out pressure holding, to intersect Flow velocity needed for being kept at region；

(4) in order to weaken adhesion of the runner inner surface to drop, reduce flow resistance, preferably in runner inner surface Hydrophobic material is coated, drop is made to be easier to flow out runner, the runner of rectangular section is more convenient when coating hydrophobic material, Also thickness is uniform after being easily guaranteed that material coating；

(5) be conducive to make the micro-fluidic chip that runner is stacked in the height direction.

Optionally, according to use demand, the cross section of first flow 1 and second flow channel 2 may be designed in it is round or Trapezoidal and other fluids that are conducive to flow, but the shape of damage will not be caused to the cell being sheared in phase fluid.

According to the analysis of front, the micro-fluidic chip of the utility model embodiment can protected by increasing channel size On the basis of demonstrate,proving cell activity, the formation efficiency of drop is improved.After channel size increase, first flow 1 is located at intersection region Upstream position is arranged nozzle and both is within the protection scope of the present invention with the scheme for being not provided with nozzle.

Since there is nozzle the conical outlet of tapered configuration to be easy to strike cone mouth wall surface when cell is flowed out from cone mouth, Also cell activity can be caused to decline cell damage.In order to further improve cell activity, in the another of the utility model In a embodiment, enlarged drawing as shown in Figure 3 cancels the nozzle that first flow 1 is located at intersection region upstream end, makes first flow 1, which is located at portion size of the intersection region upstream for trandfer fluid, is consistent.Alternatively, first flow 1 is located at the zone of intersection Domain upstream end is in increase tendency along the flow direction size of phase fluid is sheared, as long as first flow 1 is located on intersection region The size of trip is not in tapered configuration, both is within the protection scope of the present invention.

The advantages of embodiment, is that it is possible to reduce to be sheared when phase fluid flows in first flow 1 and be caused to cell Injury, so as under the premise of improving drop yield ensure cell activity.Although after cancelling nozzle, phase fluid is sheared Flow velocity decrease, the shearing force to being sheared phase fluid offer reduces, but be sheared phase flow velocity still has after reduction Enough shearing forces will be sheared phase fluid and separate.If the viscosity for being sheared phase is larger, when needing the shearing force of bigger, By finely tuning two-phase flow velocity shearing phase fluid can be made still to have sufficiently large shearing force, cell solution is dispersed into drop.

The utility model micro-fluidic chip specifically adoptable structure type is given below.Optionally, micro-fluidic chip can Using folder stream focus type runner or T-type runner.Folder stream focus type runner or T-type runner are conducive to adjust the size of drop, generate Rate also helps the damage for reducing and generating drop in the process to the active material in drop.

In a type of embodiment, the both sides of first flow 1 are respectively equipped with a second flow channel 2, the two second Shearing phase fluid can be each led into runner 2, to form folder stream focus type runner in intersectional region.Being sheared phase fluid can be from One end of first flow 1 is passed through, and shearing phase fluid is passed through from two second flow channels 2 respectively, utilizes the flowing speed of shearing phase fluid Degree can provide certain shearing force to phase fluid is sheared, while using the unstability of fluid, be sheared phase fluid and being divided From at discrete drop.Folder stream focus type runner can not only generate the better microlayer model of monodisperse, can preferably control drop ruler It is very little, and shearing force compare T-type runner shearing force it is small, be conducive to keep cell activity.

Preferably, as shown in figure 3, first flow 1 and two second flow channels 2 form criss-cross construction in intersectional region, Angle i.e. between first flow 1 and two second flow channels 2 is 90 °.

With reference to figure 4, and the operation principle of right-angled intersection runner micro-fluidic chip is described with the orientation of Fig. 4.It is sheared phase Fluid is flowed into from the upper end of first flow 1 in the direction of the arrow, and shearing phase fluid is respectively in the direction of the arrow from 1 both sides of first flow Second flow channel 2 flows into, and in the region that first flow 1 and two second flow channels 2 cross, shearing phase fluid is to being sheared phase fluid production The effect that raw folder stream focuses is sheared phase fluid and is separated into discrete by the effect of the symmetrical shearing force of both sides shearing phase fluid Drop.

Preferably, as shown in figure 4, two second flow channels 2 are in the L-shaped structure of intersectional region, the transverse part of L-shaped structure and One runner 1 is connected to and perpendicular to first flow 1, and the vertical part of L-shaped structure is parallel to first flow 1, and the extending direction of vertical part can To be passed through with first flow 1, to be sheared the direction of phase fluid consistent.

By setting second flow channel 2 to L-shaped structure, as shown in Fig. 2, can reduce single micro-fluidic in micro-fluidic chip The width of unit N is conducive in the case where 3 area of matrix is certain, is arranged more along the width direction interval of microfluidic cell N More microfluidic cell N, to improve the yield of drop.In addition, when needing to prepare different types of drop, it is also easier to ensure The yield of each drop demand.

Preferably, the distance between the vertical part of L-shaped structure and first flow 1 ranging from 0.1mm~20mm, the distance is with two It is calculated on the basis of the center line of a runner.For example, the distance between the vertical part of L-shaped structure and first flow 1 can be 0.1mm, 0.5mm, 1mm, 3mm, 5mm, 8mm, 10mm, 12mm, 15mm, 18mm, 20mm etc..

When the shearing phase fluid flowed into from L-shaped vertical part passes through bending place, the flow direction of element of fluid and flow velocity otherness It is larger, if the distance between the vertical part of L-shaped structure and first flow 1 are too small, the shearing of L-shaped structure transverse part is entered from bending place Phase fluid also has little time to form stable flow velocity and flow direction, just has begun to shear to being sheared phase fluid, unstable Shearing force be easy to cause cellular damage, can not also ensure the size for ultimately forming drop.If the vertical part of L-shaped structure with it is first-class The distance between road 1 is excessive, is sheared phase fluid after the transverse part for entering L-shaped structure, due to being hindered by 2 inner wall of second channel The effect of power, be easy to cause flow rate attenuation, the final shearing force influenced to being sheared phase fluid offer.

Therefore, the embodiment by the distance between the vertical part of L-shaped structure and first flow 1 by being chosen above range It is interior, form stable flow regime when shearing phase fluid can either be made to be flowed in L-shaped structure transverse part, using in intersectional region as quilt Shear phase fluid and stable shearing force be provided, advantageously ensure that cell activity, be also beneficial to improve the uniformity of drop size and Controllability.It can also enough decaying for reducing flow velocity when shearing phase fluid flows in L-shaped structure transverse part, with to being sheared phase Fluid provides enough shearing forces.

In addition to using right-angled intersection runner, in other embodiments, two second flow channels 2 and first flow 1 also can be in angle Degree setting, and second flow channel 2 and the angle of first flow 1 are less than 90 °.Preferably, the inclined direction phase of two second flow channels 2 Together, it tilts or is downwardly inclined upward.

More preferably, two second flow channels 2 are symmetrical arranged relative to first flow 1.It includes two second flow channels 2 to be symmetrical arranged Angle of inclination relative to first flow 1 is identical, and more into once, the length of two second flow channels 2 is also identical.Angle of inclination pair Claim the shearing force that setting can be such that both sides shearing phase fluid provides consistent, advantageously ensures that the uniformity and activity of drop size； Length, which is symmetrical arranged, to be still maintained in the case where both sides shearing phase fluid is passed through speed unanimous circumstances when reaching intersectional region Speed is consistent, so that the shearing force that both sides shearing phase fluid provides is consistent.

In another alternative embodiment, micro-fluidic chip uses T-type runner.T-type runner include third flow channel and The 4th runner of third flow channel is intersected at third flow channel.Third flow channel is for being passed through shearing phase fluid, and the 4th runner is for leading to Enter and be sheared phase fluid, shearing phase fluid will be sheared phase fluid and be divided into liquid in the intersection of third flow channel and the 4th runner Drop.

Referring to Fig. 5, solid arrow represents shearing phase fluid in Fig. 5, and dotted arrow representative is sheared phase fluid.With T-type The operation principle that the micro-fluidic chip of runner generates drop is as follows：Shearing phase fluid, horizontal run (corresponds to the from Fig. 5 respectively Three runners) it flows into, it is sheared phase fluid and is flowed into from vertical run (corresponding to the 4th runner).(correspond to the at two-phase interface The intersection of three runners and the 4th runner), it is sheared phase fluid and is acted on by the shearing force for shearing phase fluid, work as two-phase interface The interfacial tension at place is insufficiently resistant to shearing phase fluid when being applied to the shearing force for being sheared phase fluid, is sheared phase fluid fracture Generate the independent micro volume unit i.e. drop for being sheared phase fluid cladding.

On the basis of above-mentioned micro-fluidic chip, the inner surface of first flow 1 and second flow channel 2 is hydrophobic surface, tool There is hydrophobicity, can be realized by coating hydrophobic material.Preferably, first flow 1 and the inner surface of second flow channel 2 are super-hydrophobic Surface.The setting can weaken adhesion of the runner inner surface to drop when generating water-containing drop, reduce flow resistance.

Preferably, such micro-fluidic chip may be used using dimethyl silicone polymer (PDMS, Polydimethylsiloxane it) makes, and carry out hydrophobic treatment to the inner surface of the runner of drop micro-fluidic chip to make drop Hydrophobicity is presented in the inner surface of the runner of micro-fluidic chip.Glass (Glass) or polymethyl methacrylate can also be used (PMMA, polymethyl methacrylate) makes drop micro-fluidic chip, and makes to runner inner surface progress hydrophobic treatment Hydrophobicity is presented in the inner surface of the runner of drop micro-fluidic chip.The mode that hydrophobic treatment is carried out to runner inner surface is, for example, logical Octadecyl trichlorosilane alkane (OTS, octadecyltrichlorosilane) is crossed to be surface-treated.

Since the sectional dimension of first flow 1 and second flow channel 2 has a major impact the yield and activity of drop, Below by taking the micro-fluidic runner of rectangular section as an example, to illustrate the selection of channel size for cell activity in drop and yield It influences.

Preferably, the cross section of first flow 1 and second flow channel 2 is rectangle, and the length range of rectangular cross section is 0.7mm ~2mm and/or its width range are 0.2mm~0.6mm.The length and width range of rectangular cross section can meet therein one Or two all meet.

Preferably, the length value of rectangular cross section is：0.7mm、0.8mm、0.9mm、1.0mm、1.1mm、1.2mm、 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2mm etc.；The width value of rectangular section is：0.2mm、 0.25mm, 0.3mm, 0.35mm, 0.4mm, 0.45mm, 0.5mm, 0.55mm, 0.6mm etc..

For the cross type passive type micro-fluidic chip of the prior art, although drop formation can be improved by improving flow velocity An important factor for yield, flow velocity is restriction drop size, and improving flow velocity can cause shearing force to increase, although improving production Rate, but cell activity requirement cannot be met.For this purpose, the micro-fluidic chip of the utility model increases runner compared with the existing technology Size, including individually increase the length of rectangular cross section, individually increase width or increase length and width simultaneously.Below to this Several forms are analyzed respectively.

If the length increase of flow channel cross-section is individually formed very flat runner, due to the increase of cross section of fluid channel product, energy Enough increase the yield of micro-fluidic chip.But in the case where flow velocity is constant, since cross section of fluid channel is very flat, it can make to be sheared mutually to flow The shearing force that speed is subject in flow process is larger, cell may be made to be damaged, and to reduce shearing force and mean that reduction Flow velocity, to bring the reduction of yield.As it can be seen that there is the relationships mutually restricted for the yield and cell activity of drop.

During micro-fluidic chip works, two-phase flow velocity can be suitably reduced, shearing force is reduced to and disclosure satisfy that On the basis of essential biologically active, the increase accumulated by cross section of fluid channel makes up the reduction of flow velocity, to have ensured the yield of drop Increase, this just needs yield increasing increment caused by cross section of fluid channel product increase to reduce the negative effect to yield more than flow velocity.

If individually increased the width of flow channel cross-section, very flat runner is also formed, and it is individually that flow channel cross-section is wide The case where degree increases is similar.

If simultaneously increased the length and width of flow channel cross-section, such as the length of cross runner is increased into 1mm, it is wide Degree increases to 0.2mm, since cross section of fluid channel size integrally increases, is increased by the flow of cross section of fluid channel within the unit interval, can Significantly improve the yield of drop.Find that cell activity compares the prior art in the case where yield improves predetermined value by experiment It increases.For example, the size of rectangularl runner can be designed as：1.5mm×0.2mm、1mm×0.2mm、1mm×0.3mm、 0.75mm × 0.3mm, 0.75mm × 0.5mm etc..

Preferably, ranging from 200~400 μm of the diameter dimension of drop is generated by the utility model micro fluidic device. In practical operation, shearing phase fluid can be relied on and be sheared the variation control drop size of the sample introduction flow rate of phase fluid. The flow velocity for being sheared phase fluid is bigger, and the drop size of generation is bigger.The flow velocity for shearing phase fluid is bigger, generates drop size and gets over It is small.The micro-fluidic chip has the characteristics that easy to operate, repeatability is high when controlling drop size as a result,.

In a specific embodiment, use channel size for the micro-fluidic chip of 0.75mm × 0.3mm, in dispersed phase Under conditions of viscosity 1200cp, dispersion phase flow rate 15 μ L/min, 150 μ L/min of continuous phase flow rate, can obtain mean size is 300 μm of cell drop.Droplet diameter distribution figure as shown in Figure 9, cell liquid of the droplet diameter distribution at 280 μm~290 μm Drop accounts for the 40% of sum, and droplet diameter distribution accounts for the 50% of sum in 290 μm~300 μm of cell drop, cell drop it is straight Diameter average value is 291 μm.

The raw material that 3D biometric prints use is usually microballoon, and the microgel for being loaded with cell is the main raw material(s) of microballoon, is led to It crosses and microballoon is re-formed to the microgel progress droplet treatment for being loaded with cell.The microgel of cell is loaded with as phase is sheared, is sheared The viscosity of phase is usually higher, is split using the interaction of shearing force, viscous force and surface tension in liquid stream holder and generates micro- liquid Drop, therefore in the case where being sheared phase fluid viscosity far above shearing phase fluid, needing to apply larger shearing force could will Starting material solution cuts into the drop of predetermined size, this just gives the celliferous starting material solution of packet to bring damage.

The utility model is improved by convection current track forces cun, is controlled two-phase flow velocity, can be met to high viscosity The shearing force demand sheared of starting material solution, and generate the uniform drop of dispersion degree, while cell activity can be kept, It can solve the problems, such as that the micro-fluidic shearing of high viscosity starting material solution is difficult.

The micro-fluidic chip of the utility model embodiment is applicable to, in following situation, be sheared phase fluid and mutually flow with shearing Ranging from the 10 of the ratio between the viscosity of body:1~30:1, such as：10:1、12:1、14：1、15:1、17:1、18:1、20:1、22:1、 24:1、26:1、28:1、30:1。

Preferably, it is sheared ranging from 500cp~3000cp of the viscosity of phase fluid, for example, 500cp, 700cp, 1000cp、1200cp、1500cp、1800cp、2000cp、2200cp、2400cp、2600cp、2800cp、3000cp.It is more suitable The case where viscosity >=2000cp for being sheared phase fluid, the viscosity for shearing phase is smaller, is generally no more than 100cp.

In each embodiment of the utility model, cutting when first flow 1 and 2 intersectional region of second flow channel form drop Shear force is less than 100Pa.Shearing force is related to shear rate and the two influence factors of viscosity, and the flow velocity for shearing phase fluid is bigger, The shearing force being capable of providing is bigger, and the viscosity for being sheared phase fluid is bigger, and the shearing force needed is also bigger.

The phase fluid that is sheared in above-described embodiment may include core liquid, covering liquid or curing agent etc., continuous phase fluid with It is immiscible as the dispersed phase fluid for being sheared phase, it can be liquid, can also be gas.The drop for generating different materials can be with Using identical continuous phase fluid, different dispersed phase fluids can also be used.Correspondingly, micro-fluidic chip is for generating core Liquid drop, covering liquid drop or curing agent drop.

The raw material for forming drop can be the microgel for being loaded with cell, can also be the celliferous any solution of packet.Such as Can be it is naturally occurring, it is artificial synthesized, what abundance generated, it is modified or it arbitrary is combined.Wherein, it naturally deposits Raw material can be derived from the naturally occurring biodegradable materials of animals and plants, such as collagen, fibrin, Chitosan, alginate, starch, hyaluronic acid, laminin, agarose, gelatin, glucan and its arbitrary combination.

Preferably, core liquid is to wrap celliferous collagen solution, for example, collagen mixture solution.It is specific at one Embodiment in, ox type i collagen and adipose-derived mescenchymal stem cell (ADSCs) will can be mixed as being loaded with cell The core material of microgel.

Preferably, shearing phase fluid is mineral oil, edible oil, corn oil or peanut oil etc. with certain biocompatibility Oily solution.Alternatively, shearing phase fluid may be air.

For example, cell-collagen mixture and mineral oil to be injected separately into 1 He of first flow of chip by force (forcing) pump In second flow channel 2, droplet is formed since collagen-cell mixture is squeezed by two-way mineral oil stream.As shown in Figure 8 is micro- Microphoto of the discharge orifice chip at intersectional region, collagen mixture solution can passively quickly generate be dispersed in oil it is molten Collagen droplet in liquid.Further, drop is used for gelation caused by being collected by outlet.

The adoptable specific embodiment of the utility model micro-fluidic chip is given below.As shown in Figure 1, matrix 3 includes two Laminate, runner are formed between two-ply.First flow 1 is in linear type runner, has first fluid import 11 and drop outlets 12, two second flow channels 2 respectively symmetrically are located at 1 both sides of first flow, and two 2 respective one end of second flow channel are respectively equipped with solely Vertical second fluid import 21, the respective other end are connected to first flow 1, and right-angled intersection knot is formed at intersectional region Structure.

When needing to generate drop, dispersed phase fluid is passed through first flow 1 from first fluid import 11, by continuous phase stream Body is passed through corresponding second flow channel 2 from two second fluid imports 21 respectively, and both sides continuous phase fluid is in cross confluence Dispersed phase fluid is cut into discrete drop by domain, and drop is again from right-angled intersection region along the downstream flow of first flow 1, finally It is flowed out from drop outlets 12, the drop of outflow collects in container 4.

In another embodiment, as shown in Fig. 2, being equipped with multiple microfluidic cell N in matrix 3, such as 8 independent micro- Folder stream focus type runner, such as criss-cross construction, each micro-fluidic list are all had in flow control unit N, each microfluidic cell N First N can either simultaneously or alternately work.Preferably, multiple microfluidic cell N can arrange according to identical direction, or can also make Each microfluidic cell N is arranged at equal intervals.

Such micro-fluidic chip can either simultaneously or alternately generate drop to increase efficiency, or also can be by different miniflows Different raw material are passed through in control unit N, to generate different types of drop, for example, part microfluidic cell N is for generating core Core liquid drop, part microfluidic cell N is for generating covering liquid drop or part microfluidic cell N for generating curing agent Drop.

For each microfluidic cell N, first flow 1 is connected to second flow channel 2, and cross is formed at intersectional region Chi structure.First flow 1 is at linear type structure, and second flow channel 2 includes enclosing rectangularl runner, and first flow 1 is located at rectangle In the region that runner surrounds, the first end of first flow 1 and rectangularl runner short side cross and extend outward to form confession Another short side of the runner of drop discharge, the second end and rectangularl runner separates, for being passed through dispersed phase stream from the second end Body.Short side of the rectangularl runner far from right-angled intersection region, which is equipped with, extends runner, for being passed through continuous phase stream into rectangularl runner The both ends of body, i.e., two second flow channels 2 are passed through shearing phase fluid by common fluid inlet.

The drop obtained by micro-fluidic chip, is all that many kinds of parameters is coefficient in terms of yield and cell activity As a result, such as flow channel shape, channel size, fluid viscosity, shearing phase fluid and the flow control for being sheared phase fluid.Passing through When specific micro-fluidic chip makes certain raw material form drop, the performance in terms of yield and cell activity depends primarily on two-phase Flow control.

Based on above-described embodiment micro-fluidic chip, in order to obtain suitable drop size, and ensure the yield of drop and thin Cytoactive, it is also necessary to which shearing phase fluid and the flow velocity for being sheared phase fluid are controlled.The flowing velocity of two-phase can pass through Flow parameter reflects, in a preferred embodiment, is sheared phase fluid and shears phase fluid at the intersectional region with single channel Ranging from the 1 of the ratio between flow:10~1:20.For example, 1:10、1:11、1:12、1:13、1:14、1:15、1:16、1:17、1:18、 1:19、1:20。

More preferably, range of flow of the single channel shearing phase fluid at intersectional region is the 100 μ L/min of μ L/min~400, example Such as, 100 μ L/min, 150 μ L/min, 200 μ L/min, 250 μ L/min, 300 μ L/min, 350 μ L/min, 400 μ L/min.It is cut Range of flow of the cut phase fluid at intersectional region is the 10 μ L/min of μ L/min~40, for example, 10 μ L/min, 15 μ L/min, 20 μ L/min、25μL/min、30μL/min、35μL/min、40μL/min。

For example, for the runner of criss-cross construction, the second flow channel 2 of 1 both sides of first flow is passed through shearing phase fluid Range of flow may each be 100 μ of μ L/min~400 L/min, it is preferable that being sheared mutually in confluence in both sides second flow channel 2 The flow velocity in domain is consistent, uniform force when ensureing to form drop.

In a specific embodiment, the cross section of first flow 1 and second flow channel 2 is rectangle, rectangular cross section Length range is 0.7mm~2mm, and width range is 0.2mm~0.6mm.For example, first passage 1 and second channel 2 form ten Word chi structure.It is sheared phase fluid to flow into from first flow 1, two of shearing phase fluid from 1 both sides of first flow are first-class Road 2 separately flows into.Preferably, ranging from the 10 of the ratio between phase fluid and the viscosity of shearing phase fluid are sheared:1~30:1.Into one Step ground, is sheared ranging from 500cp~3000cp of the viscosity of phase fluid.It, can be to the flow of two-phase fluid when preparing drop It is controlled.For example, be sheared phase fluid and single channel shear phase fluid at intersectional region the ratio between flow ranging from 1:10~ 1:20.More preferably, it is 10 μ of μ L/min~40 L/ that range of flow of the phase fluid at intersectional region is sheared in first passage 1 Min, range of flow of the shearing phase fluid at intersectional region all can be 100 μ of μ L/min~400 L/ in each second channel 2 min.By carrying out flow control to the micro-fluidic chip in the specific embodiment, the diameter dimension of drop can get ranging from 200 μm~400 μm.

The utility model also runner based on criss-cross construction, two-phase mixture integrates during sunykatuib analysis drop generates Number and suffered shearing force.

Fig. 6 illustrates two-phase volume fraction simulation drawing.Dispersed phase fluid is flowed into from one end of first flow 1, continuous phase Fluid is flowed into from the second flow channel 2 of both sides, and in cross intersectional region, continuous phase fluid gradually wraps up discrete phase fluid, makes friendship The dispersed phase fluid converged in region becomes reverse taper portion, under the pressure effect of dispersed phase fluid, the part in intersectional region Continue flow forward, so that reverse taper portion is progressively disengaged mainstream beam under the shear action of continuous phase fluid, ultimately form drop Intersect the downstream flow in region.The outside of drop is still enclosed with a certain amount of continuous phase fluid at this time, while in first flow 1 It is full of continuous phase fluid in the runner in intersection region downstream, discrete drop is driven to flow outward.

Fig. 7 illustrates the simulation drawing to form suffered shearing force during drop.In the right-angled intersection region for generating drop Place, for continuous phase fluid in the lower part of reverse taper portion, since size becomes smaller under the squeezing action of continuous phase fluid, herein The shearing force being subject to is more than other positions.And in the both sides of reverse taper portion and the junction of dispersed phase fluid mainstream beam, by In also by the squeezing action of continuous phase fluid, with the movement of discrete phase fluid, reverse taper portion and dispersed phase fluid mainstream Beam will be disengaged from, thus the region is also by larger shearing force.

Illustrate that the micro-fluidic chip of the utility model is improving cell activity and raising below by specific embodiment The contribution of yield aspects.It is tested by taking the micro-fluidic chip of criss-cross construction as an example, and mentioned in following embodiments Continuous phase flow rate refers to the sum of the flow of continuous phase fluid in two second flow channels 2.Each embodiment is as follows：

Experiment 1 uses channel size for the device of 1mm × 0.3mm, in dispersed phase viscosity 2400cp, 20 μ of dispersion phase flow rate Under conditions of L/min, 300 μ L/min of continuous phase flow rate, the cell drop that mean size is 220 μm, average cell can be obtained Activity is not less than 88%.

Experiment 2 uses channel size for the device of 1mm × 0.3mm, in dispersed phase viscosity 2400cp, 20 μ of dispersion phase flow rate Under conditions of L/min, 200 μ L/min of continuous phase flow rate, the cell drop that mean size is 350 μm, average cell can be obtained Activity is not less than 90%.

Experiment 3 uses channel size for the device of 0.75mm × 0.3mm, in dispersed phase viscosity 1200cp, disperses phase flow rate Under conditions of 15 μ L/min, 150 μ L/min of continuous phase flow rate, the cell drop that mean size is 300 μm can be obtained, it is average thin Cytoactive is not less than 95%；

Experiment 4 uses channel size for the device of 0.75mm × 0.3mm, in dispersed phase viscosity 1200cp, disperses phase flow rate Under conditions of 40 μ L/min, 800 μ L/min of continuous phase flow rate, the cell drop that mean size is 200 μm can be obtained, it is average thin Cytoactive is not less than 80%.

As a comparison, the micro-fluidic chip that channel size is 0.5mm × 0.1mm in the prior art, for conveying dispersed phase It is 60 μm of nozzle arrangements that the runner of fluid is equipped with outlet in right-angled intersection region, is only capable of in dispersed phase viscosity 1200cp, dispersed phase Under conditions of flow 2 μ L/min, 30 μ L/min of continuous phase flow rate, the cell drop of 180 μm of average-size, and average cell are generated Activity is not higher than 85%.

Four groups of experiments are carried out by the micro-fluidic chip to the utility model, and are compared with the prior art.

(1) it is sheared phase viscosity：

For the prior art when dispersed phase viscosity is 1200cp, dispersion phase flow rate is 2 μ L/min, if dispersed phase viscosity continues Increase, continuous phase fluid increases the shearing difficulty of dispersed phase fluid, understands the yield that basic mountain herein further decreases drop.And For the embodiments of the present invention when dispersed phase viscosity is 2400cp, dispersion phase flow rate can still reach 20 μ L/min, therefore right In highly viscous dispersed phase fluid the yield of drop can be also improved while ensureing cell activity.

(2) drop size：

The average-size for the cell drop that prior art runner generates is 180 μm, and what the utility model embodiment generated The average-size of cell drop is 200 μm, 220 μm, 300 μm and 350 μm, and it is 200 μ to meet the aforementioned drop size range provided M~400 μm can preferably meet the needs of biological 3D printing.Moreover, dispersion phase flow rate is bigger, the drop size of generation is got over Greatly, the drop size of the bigger generation of continuous phase flow rate is smaller, by the Comprehensive Control of two phase flow, can steadily obtain required The drop size wanted.

(3) cell activity：Experiment 1 and experiment 2 are compared, the two channel size is identical, dispersed phase viscosity is identical In the case of identical with dispersion phase flow rate, discrete phase flow rate is bigger, and the shearing force for generating the generation at intersectional region is bigger, to thin The activity influence of born of the same parents is bigger, but disclosure satisfy that demand of the 3D biometric prints to cell activity.

Experiment 3 and experiment 4 are compared, it is identical identical with dispersed phase viscosity in the two channel size, it is real 4 are tested than experiment 3 while increasing dispersion phase flow rate and continuous phase flow rate.The increase of dispersion phase flow rate can make fluid and first flow The frictional force of 1 inner wall increases, and the shearing force being subject in flow process so as to cause dispersed phase fluid increases；Continuous phase flow rate Increasing can make continuous phase fluid increase the shearing force of dispersed phase fluid, the two factors all can generate shadow to the activity of cell It rings.As it can be seen that the increase of channel size helps to reduce the shearing force that dispersed phase fluid is subject in flow process.

Meanwhile the limit flow of two-phase is also obtained by experiment 4, under limit flow, cell activity still is able to meet The requirement of 3D biometric prints.

(4) drop yield：

Since dispersed phase fluid is basically used for generating drop, waste of material is less, thus the yield of drop can use dispersion The consumption of phase fluid is evaluated.In being tested at four, 20 μ L/min of dispersion phase flow rate, 20 μ L/min, 15 μ L/min and 40 μ L/ Min, and it is only 2 μ L/min to disperse phase flow rate in the prior art, it is seen that the dispersion phase flow rate of the utility model is the prior art 7.5 times, even up to 20 times, substantially increase the yield of drop.

It is described by above-described embodiment to micro-fluidic chip, the utility model is increased by designing cross section of fluid channel size Big fluid course, and be located at the partial cancellation nozzle arrangements of intersection region upstream in first flow 1, and by flow control, It can be finally so that high viscosity cell solution generates the efficiency of drop and cell activity is promoted, to meet the needs of 3D printing.No Only can be that 3D printing equipment supplies microballoon at faster speed, additionally it is possible to meet the cell activity needed for 3D biometric prints.

Thus, such micro-fluidic chip can solve high viscosity (referring generally to be sheared phase viscosity much larger than shearing phase viscosity) Wrap the drop that celliferous hydrogel generates large scale (200 μm~400 μm of diameter), ensure cell activity (60%-80% with On) while need at least improve 30% or more yield.

In addition, the utility model additionally provides a kind of drop formation device, including the micro-fluidic core described in above-described embodiment Piece.

Preferably, micro-fluidic chip is removably disposed.This is provided with to replace the micro-fluidic core of drop of different model Piece is to change the diameter of drop, to prepare various sizes of microballoon.

Further, it is successfully passed into corresponding runner in order to shear phase fluid and be sheared phase fluid, The micro fluidic device of the utility model further includes pumping installations, and pumping installations is connected to first flow 1 and second flow channel 2, is used for Control is sheared the speed and flow that phase fluid enters first flow 1, and shearing phase fluid enters the speed in second flow channel 2 And flow.Pumping installations can control flow by controlling the pressure of fluid, convenient for accurately controlling two phase flow.

Further, the drop formation device of the utility model further includes input part, input part with first flow 1 With the inlet communication of second flow channel 2, the fluid for being used to form drop to first flow 1 and the conveying of second flow channel 2.Or liquid Drop generating means further include output block, output block and output block, output block and first flow 1 and second flow channel 2 Outlet, the drop output for that will be formed.

Wherein, for input part for example including inputting communicating pipe, input preferably includes input capillary communicating pipe.Input unit Part can be specifically divided into the input part for inputting dispersed phase fluid and the input part for inputting continuous phase fluid.Output For component for example including exporting communicating pipe, output preferably includes output capillary communicating pipe.

Finally, the utility model additionally provides a kind of microballoon preparation facilities, including the drop formation described in above-described embodiment Device.By microballoon preparation facilities generate microballoon substantially method be：Core liquid is passed through into micro-fluidic chip first to pass through Generate core liquid drop；Core liquid drop is then accordingly dropped to the action face in the different collection holes for collecting manufacture main body On；Then core liquid droplet formation microballoon is based in the action face for collecting hole.

Preferably, microballoon is the material of the biological prepared Chinese ink for biological 3D printing, and microballoon includes cell.

The microballoon preparation facilities of the utility model can produce not stratified single chondritic or layering chondritic.

For example, microballoon can be layering chondritic, composition may include at least the one of one layer of core and encapsulation core Layer clad.Core includes cell, and cell can be grown, be proliferated, broken up or be migrated, the substance in core liquid other than cell It is made of biodegradable material, and required substance is provided for the vital movement of cell.Clad can be by biodegradable Material is made, and provides mechanics protection for internal core and cell, and the layering chondritic of this preferred structure can be made For the core component of biological prepared Chinese ink, the i.e. base unit as 3D biometric prints.

The microballoon prepared by the utility model can be used for multiple fields, such as biometric print (such as 3D biometric prints), group The fields such as weaver's journey, regenerative medicine.

A kind of micro-fluidic chip provided by the utility model, drop formation device and microballoon preparation facilities are carried out above It is discussed in detail.Specific embodiment used herein is expounded the principles of the present invention and embodiment, with The explanation of upper embodiment is merely used to help understand the method and its core concept of the utility model.It should be pointed out that for this skill For the those of ordinary skill in art field, without departing from the principle of this utility model, can also to the utility model into Row some improvements and modifications, modifications and modifications also fall within the protection scope of the claims of the utility model.

Claims (23)

1. a kind of micro-fluidic chip, which is characterized in that including matrix (3) and the first flow (1) being located in described matrix (3) and Second flow channel (2), the first flow (1) and second flow channel (2) intersection and form intersectional region, being sheared phase fluid can be from The first flow (1) flows into, and shearing phase fluid can be flowed into from the second flow channel (2), to be incited somebody to action in the intersectional region The phase fluid that is sheared is separated into discrete drop, and the sectional area of the first flow (1) and second flow channel (2) is ranging from 0.1mm²~1mm²。

2. micro-fluidic chip according to claim 1, which is characterized in that the first flow (1) is located on intersection region The portion size of trip is consistent, or along be sheared phase fluid flow direction size be in increase tendency.

3. micro-fluidic chip according to claim 1, which is characterized in that the both sides of the first flow (1) are respectively equipped with One second flow channel (2), to form folder stream focus type runner in the intersectional region.

4. micro-fluidic chip according to claim 3, which is characterized in that the first flow (1) and two described second Runner (2) forms criss-cross construction in intersectional region.

5. micro-fluidic chip according to claim 4, which is characterized in that each second flow channel (2) is in intersectional region L-shaped structure, the transverse part of the L-shaped structure are connected to the first flow (1) and perpendicular to first flow (1), the L-shaped The vertical part of structure is parallel to the first flow (1).

6. micro-fluidic chip according to claim 5, which is characterized in that the vertical part of the L-shaped structure with it is described first-class The distance between road (1) ranging from 0.1mm~20mm.

7. micro-fluidic chip according to claim 3, which is characterized in that two second flow channels (2) and described first Runner (1) angled setting, the second flow channel (2) and the angle of first flow (1) are less than 90 °.

8. micro-fluidic chip according to claim 3, which is characterized in that two second flow channels (2) are relative to described First flow (1) is symmetrical arranged.

9. micro-fluidic chip according to claim 1, which is characterized in that the first flow (1) and second flow channel (2) Cross section is rectangle, circle or trapezoidal.

10. micro-fluidic chip according to claim 1, which is characterized in that the first flow (1) and second flow channel (2) Cross section be rectangle, the length range of the rectangular cross section be 0.7mm~2mm and/or its width range be 0.2mm~ 0.6mm。

11. micro-fluidic chip according to claim 1, which is characterized in that described to be sheared phase fluid and the shearing phase Ranging from the 10 of the ratio between the viscosity of fluid:1~30:1.

12. micro-fluidic chip according to claim 11, which is characterized in that the range of the viscosity for being sheared phase fluid For 500cp~3000cp.

13. micro-fluidic chip according to claim 1, which is characterized in that the phase fluid that is sheared shears phase with single channel Fluid at the intersectional region the ratio between flow ranging from 1:10~1:20.

14. micro-fluidic chip according to claim 13, which is characterized in that shear phase fluid described in single channel and cross described Range of flow at region is 100~400 μ L/min, and the range of flow for being sheared phase fluid at the intersectional region is 10~40 μ L/min.

15. micro-fluidic chip according to claim 1, which is characterized in that ranging from 200 μm of the diameter dimension of the drop ~400 μm.

16. micro-fluidic chip according to claim 3, which is characterized in that the both ends of two second flow channels (2) pass through Common fluid inlet is passed through the both ends of the shearing phase fluid or two second flow channels (2) respectively by independent Fluid inlet is passed through the shearing phase fluid.

17. micro-fluidic chip according to claim 1, which is characterized in that be equipped with multiple micro-fluidic lists in described matrix (3) First (N) each all has folder stream focus type runner in the microfluidic cell (N), each microfluidic cell (N) can be same When or alternation.

18. micro-fluidic chip according to claim 1, which is characterized in that the phase fluid that is sheared includes core liquid, packet Covering liquid or curing agent, the micro-fluidic chip are used to form core liquid drop, covering liquid drop or curing agent drop.

19. micro-fluidic chip according to claim 18, which is characterized in that the core liquid is that the celliferous collagen of packet is molten Liquid, the shearing phase fluid are oil-based solvent.

20. a kind of drop formation device, which is characterized in that including any micro-fluidic chip of claim 1~19.

21. drop formation device according to claim 20, which is characterized in that further include pumping installations, the pumping dress It sets and is connected to the first flow (1) and second flow channel (2), phase fluid is sheared into the first flow (1) for controlling Speed and flow, and shearing phase fluid enter the second flow channel (2) in speed and flow.

22. drop formation device according to claim 20, which is characterized in that further include input part, the input unit Inlet communication of the part with the first flow (1) and second flow channel (2) is used for the first flow (1) and second flow channel (2) conveying is used to form the fluid of drop；Or

The drop formation device further includes output block, the output block and the output block, the output block with The outlet of the first flow (1) and second flow channel (2), the drop output for that will be formed.

23. a kind of microballoon preparation facilities, which is characterized in that including any drop formation device of claim 20~22.