CN107418872A

CN107418872A - Prepare the device of microballoon and prepare the method for microballoon

Info

Publication number: CN107418872A
Application number: CN201610786492.0A
Authority: CN
Inventors: 张雅雅; 温学敏
Original assignee: Sichuan Revotek Biotechnology Co Ltd
Current assignee: Sichuan Revotek Biotechnology Co Ltd
Priority date: 2016-08-31
Filing date: 2016-08-31
Publication date: 2017-12-01

Abstract

The present invention provides a kind of device for preparing microballoon and the method for preparing microballoon.Preparing the device of microballoon includes：Drop formation module, including first fluid entrance, drop micro-fluidic chip and output port, drop micro-fluidic chip includes runner system, first fluid entrance and output port connect with runner system respectively, and the dispersed phase fluid entered from first fluid entrance in air stream enter runner system forms drop and exports drop from output port；Collect manufacture module, main body is manufactured including collecting, multiple collection holes that manufacture main body includes each having action face are collected, each action face for collecting hole is isolated from each other, collects hole and drop to action face for reception liquid and droplet formation microballoon is based in action face；Motion module, main body drive connection is manufactured with output port and/or collection, so that each drop is accordingly dropped in the action face for collecting hole；Control module, coupled respectively with drop formation module and motion module.The device for preparing microballoon can prepare the microballoon for meeting Particle size requirements.

Description

Prepare the device of microballoon and prepare the method for microballoon

Technical field

The present invention relates to microsphere preparation technology field, more particularly, to the biological prepared Chinese ink preparation field of biometric print, especially It is related to a kind of device for preparing microballoon and the method for preparing microballoon.

Background technology

The biological prepared Chinese ink in biometric print field includes the microballoon with bioactivity.The microballoon is generally celliferous to wrap Collagen solution is as main raw material(s).When making microballoon, first using the main raw material(s) as the constituent for forming core Core liquid be divided into the core liquid drop of predetermined size size, then based on the core liquid droplet formation microballoon, to meet 3D biologies The demand of biological tissue or organ is formed during printing.The microballoon of prior art is typically not stratified single chondritic, now, Single chondritic only solidifies postforming by core liquid drop.

Biological 3D printing field to for biological prepared Chinese ink microballoon prepare shaping after particle diameter and dimensional uniformity have compared with High requirement, and microballoon made from needs has biological function and certain mechanical strength concurrently.

In the prior art, when manufacturing the biological prepared Chinese ink needed for biological 3D printing, mainly core is generated by following two methods Core liquid drop：

First, using vibration or impulse method liquid separation.

Mainly acted on using superpositing vibration, the liquid jet of laminar condition is divided into equal sized drop, generate liquid The particle diameter and quantity of drop are related to the vibration selected or pulse frequency.It is larger using size droplet diameter made from vibration or impulse method, The particle size range of the drop generated is typically 0.15~2mm.

2nd, using micro liquid liquid separating meter liquid separation.

Make liquid liquid separation to micro-scale volume using the principle of air slide.By accurate sample introduction syringe needle and follow-up liquid separation Power set, the liquid measure minimum that can get is in 0.1 μ L, and its obtained size droplet diameter is generally more than 500 μm.Micro liquid point Liquid instrument can be liquid-transfering gun or accurate sample introduction needle etc..

Present applicant also proposed a kind of microballoon with bioactivity for biological prepared Chinese ink.The microballoon is edge The layering chondritic that the radially layered of microballoon is set.

Layering chondritic is usually that the materials such as solid, liquid or gas are coated on into filmogen using filmogen In, its a diameter of 1~1000 μm.Core and two layers of the clad in core radial outside can for example be included by being layered chondritic Structure.Core is formed by core liquid, and clad is then formed by covering liquid.

Because biological tissue and organ caused by biometric print technology are required to have certain biological function, therefore, For biological prepared Chinese ink the foregoing layering chondritic with bioactivity core generally by wrapping celliferous collagen solution shape Into.When preparing layering chondritic, it is necessary to re-form clad outside core.Because the structure of biological tissue and organ is non- Often fine, therefore, the particle diameter of the layering chondritic usually requires control between 10~200 μm, and dimension precision requirement It is very high.

Layering chondritic is prepared using biochemical room laboratory hand preparation technology in the prior art, most common of which The method for preparing microballoon is orifice method.Core liquid and covering liquid are generally mixed to form mixed solution by orifice method, then to containing Have the droppers such as dropper or the syringe of the mixed solution of core liquid and covering liquid apply vibration or voltage pulse will mix it is molten Drop enters in curing agent, and mixed solution is rapid in curing agent to be solidified so as to form layering chondritic.

Correspondingly, the existing device for preparing microballoon, layering chondritic is generally also prepared based on orifice method.It is wrapped Include vibration (or pulse) bringing device, dropper and the reaction vessel being arranged on below dropper.Wherein, vibrate (or arteries and veins Punching) bringing device applies the vibration of certain frequency and certain amplitude to the flow channel position of the solution in dropper makes solution Jet breakup forms the drop of predetermined size size.Dropper then will mixing in the presence of (or pulse) bringing device is vibrated Solution is instilled in reaction vessel.Curing agent is contained with reaction vessel, the mixed solution instilled in reaction vessel is in curing agent Layering chondritic is formed by curing under effect.

During the present invention is realized, designer studies discoverys by analysis, the existing method for preparing microballoon with The problem of following several respects be present in the device for preparing microballoon：

1st, manufacturing the core liquid drop needed for the microballoon of biological prepared Chinese ink generally has special performance requirement, using vibrating or The performance of drop made from the easy influence of impulse method liquid separation.If for example, require in core liquid drop containing biologically active cell, The particle diameter of core liquid drop is smaller, hundreds of microns of particle diameter, such as 10~200 μm, using vibration or impulse method liquid separation just It is difficult to the preparation requirement for meeting the core liquid drop.The less particle diameter of core liquid drop is intended to higher vibration frequency Rate, and during the liquid separation using higher vibration frequency would generally to core liquid in the cell that contains cause serious infringement and Influence, realized so as to influence the active and biological sexual function of cell.Similarly, for layering chondritic, by vibration or Impulse method carries out liquid separation, can also influence the performance and layering result of core liquid and covering liquid, such as higher material of viscosity may The shape disunity that each liquid separation amount is uneven and/or liquid separation is formed can be produced.Therefore, liquid separation is carried out by vibration or impulse method The performance of chondritic can be influenceed to be layered, contained carefully particularly with the layering chondritic that can require of having specific characteristics, such as core Born of the same parents and/or require each and be layered the layering chondritic that accurately distinguishes, the adverse effect of vibration or pulse liquid separation method is more prominent.

2nd, the particle diameter for the microballoon being prepared is larger.In the biological prepared Chinese ink manufacture of 3D biometric prints, core is typically required The particle diameter of liquid drop is 5 μm~120 μm, and the particle diameter of microballoon is 10~200 μm.And use micro liquid liquid separating meter liquid separation such as dropper Or syringe is added dropwise, each dripping quantity is more, and drop size is larger, it is difficult to by the size controlling of obtained drop in 500 μ Below m, it is impossible to the Particle size requirements of core liquid drop or microballoon when meeting to manufacture biological prepared Chinese ink.During manufacture layering chondritic, by It is directly related with solution dripping quantity in the particle diameter of layering chondritic, therefore, the particle diameter of preparation-obtained layering chondritic Also it is larger, generally more than 500 μm, it is difficult to meet the Particle size requirements that chondritic is layered in the technical fields such as biometric print.

Scale error is larger when the 3rd, preparing layering chondritic, it is difficult to ensures the dimensional accuracy of layering chondritic.Using When dropper or syringe are to realize the absorption of core liquid and covering liquid and dropwise addition, because dropper and syringe can not be accurately and real When react its amount of solution drawn, required accordingly, it is difficult to ensure that solution that dropper and syringe draw every time meets to prepare, Dropper and syringe are also difficult to control the precision of each dripping quantity.This actual dripping quantity and default dropwise addition when can cause to be added dropwise every time Amount is different, and actual particle size and the predetermined size error for being layered chondritic are larger.Therefore, prior art is difficult to ensure that layering is spherical The dimensional accuracy of structure.Moreover, will also result in the accuracy for being difficult to ensure that repeatedly, repeating component titration process, can not both ensure The uniformity of gradation dripping quantity when repeating to prepare, it is difficult to meet that the structure that different batches are layered with chondritic is consistent with particle diameter Property require, can not realize batch standardization prepare, it is also difficult to ensure not homogeneous dripping quantity be changed according to default difference, meet In some cases to the personalized otherness requirement of microballoon.Also it is difficult to have for example, the prior art for preparing microballoon is combined There are the batch of the layering chondritic of multilayer different-thickness clad, standardization to prepare.

4th, the forming shape of the unmanageable layering chondritic of the existing device for preparing microballoon.Prepared based on prior art When being layered chondritic, nucleocapsid mixed solution, which is directly instilled in curing agent, to be solidified, the shape of core and the shape of clad It is to be formed in the curing process by each chemical reaction of itself, and the forming shape of core and clad is not added With control.Therefore, the forming shape of core and clad is difficult to be effectively controlled, and the forming shape of core and clad is random Property is larger, and the sphericity of core is poor, and the sphericity for the clad being coated in core is also poor, and the layering ultimately formed is spherical The molding effect of structure is unsatisfactory.The shape for being additionally, since core is formed by itself chemical reaction, and this is also required Core liquid itself have is easy to be shaped to the characteristics of spherical so that in the prior art can use core liquid range of choice by Limitation, some, which cannot be easily shaped into spherical material and are difficult by prior art, prepares to form satisfactory layering chondritic. And this also results in the preparation that prior art is difficult to some layering chondritics, the hair of some particular technology areas can be hindered Exhibition, for example, collagen need could be molded under given conditions, based on prior art be difficult by collagen be directly prepared into layering it is spherical Structure.

5th, cumbersome, efficiency is low.The device for preparing microballoon of prior art and prepare the method for microballoon and be generally all Core liquid drop and/or covering liquid drop are collected and solidified in a manner of manual or be automanual, the preparation process of microballoon Need largely to intervene manually operated.Also, extraneous sampling device or collection device, driving control system are usually external macroscopical Precise injection pump or compression pump etc., larger there is whole system, wiring is more, it is necessary to the shortcomings of professional operates.

It can be seen that the existing device for preparing microballoon is difficult to meet the microballoon needed for biological prepared Chinese ink with the method for preparing microballoon Prepare require, exist particle diameter is larger, forming shape is bad, unified size and standardization are difficult to ensure that between microballoon and is unfavorable for after Continuous process, it is less efficient the defects of, but also infringement cytoactive be present, hinder cell biological function to realize, can not repeat In batches, standardization prepares or repeated the personalized preparation of difference, can not realize that the microballoon compared with small particle is prepared, to preparing microballoon The problems such as material limitation requires more, and microballoon shaping situation is uncontrollable, less efficient, is particularly difficult to satisfaction and prepares needed for tissue A large amount of biological microspheres repetitive lotses, standardization demand.

The content of the invention

A technical problem to be solved by this invention is：The existing device for preparing microballoon and the method hardly possible for preparing microballoon The problem of to meet Particle size requirements.

In order to solve the above-mentioned technical problem, first aspect present invention provides a kind of device for preparing microballoon, including：Drop Generation module, the drop formation module include first fluid entrance, drop micro-fluidic chip and output port, and the drop is micro- Fluidic chip includes runner system, and the first fluid entrance and the output port connect with the runner system respectively, the liquid Drip micro-fluidic chip be used for will from the first fluid entrance enter the runner system in dispersed phase fluid formed drop and from The output port exports the drop；Manufacture module is collected, the manufacture module of collecting includes collecting manufacture main body, the receipts Collection manufacture main body includes multiple collection holes each with action face, and each action face for collecting hole is isolated from each other, the receipts Collection hole is used to receive the drop to the action face and microballoon described in the droplet formation is based in the action face； Motion module, the motion module manufactures main body drive connection with the output port and/or described collect, for described defeated Relative motion is produced between exit port and the collection manufacture main body so that each drop accordingly drops to the collection hole In the action face；Control module, the control module are coupled with the drop formation module to control the drop formation Module generates the drop, and the control module is coupled with the motion module to control the motion module to act.

In the device for preparing microballoon of the present invention and the method for preparing microballoon, it can be generated using drop formation module i.e. full The drop of sufficient Particle size requirements and accordingly instilling drop in different collection holes can prevent multiple orbicules from completing preparing Before influence each other；Microballoon is formed in action face, is advantageous to control the shapes and sizes of microballoon.Therefore, this prepares microballoon Each part close ties of device, it is fitted to each other, the microballoon for meeting Particle size requirements can be prepared.Further, moreover it is possible to prepare Meet the microballoon of bioactivity.The device for preparing microballoon is adapted to the preparation of various microballoons, the microsize that is particularly suitable for use in and/or The preparation of microballoon for possessing bioactivity is needed, such as is adapted to the microballoon for preparing biological prepared Chinese ink.

Second aspect of the present invention provides a kind of method for preparing microballoon, including：Core liquid drop formation and collection step, Including：Core liquid is passed through into drop micro-fluidic chip to generate core liquid drop by the drop micro-fluidic chip；By institute Core liquid drop is stated accordingly to drop in the action face in the different collection holes for collecting manufacture main body；Microballoon generation step, bag Include：Microballoon described in the core liquid droplet formation is based in the action face in the collection hole.

The method for preparing microballoon of the present invention can produce the similar technology of aforementioned techniques effect of device with preparing microballoon Effect.

By referring to the drawings to the present invention exemplary embodiment be described in detail, further feature of the invention and Its advantage will be made apparent from.

Brief description of the drawings

In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing There is the required accompanying drawing used in technology description to be briefly described, it should be apparent that, drawings in the following description are only this Some embodiments of invention, for those of ordinary skill in the art, without having to pay creative labor, may be used also To obtain other accompanying drawings according to these accompanying drawings.

Fig. 1 is the schematic diagram of the device for preparing microballoon of first embodiment of the invention.

Fig. 2 is the company of drop formation module and reagent memory module in the device for preparing microballoon of first embodiment of the invention Connect schematic diagram.

Fig. 3 is the drop micro-fluidic chip of drop formation module in the device for preparing microballoon of first embodiment of the invention Schematic diagram.

Fig. 4 is the drop micro-fluidic chip of drop formation module in the device for preparing microballoon of first embodiment of the invention Principle schematic.

Fig. 5 be first embodiment of the invention an alternate embodiment in drop micro-fluidic chip principle schematic.

Fig. 6 is that the collection that manufacture module is collected in the device for preparing microballoon of first embodiment of the invention manufactures showing for main body It is intended to.

Fig. 7 is that one kind that manufacture module is collected in the device for preparing microballoon of first embodiment of the invention optionally collects system Make the cross section structure diagram of main body.

To be collected in the device for preparing microballoon of invention first embodiment, the another kind of manufacture module is optional to be collected Fig. 8 sheets Manufacture the cross section structure diagram of main body.

Fig. 9 is another optional collection that manufacture module is collected in the device for preparing microballoon of first embodiment of the invention Manufacture the cross section structure diagram of main body.

Figure 10 is the schematic diagram of the device for preparing microballoon of second embodiment of the invention.

Figure 11 is the structure for the drainage structure that manufacture module is collected in the device for preparing microballoon of second embodiment of the invention Schematic diagram.

Embodiment

Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, rather than whole embodiments.Below Description only actually at least one exemplary embodiment is illustrative, is never used as to the present invention and its application or makes Any restrictions.Based on the embodiment in the present invention, those of ordinary skill in the art are in no development creative work premise Lower obtained every other embodiment, belongs to the scope of protection of the invention.

It may be not discussed in detail for technology, method and apparatus known to person of ordinary skill in the relevant, but suitable In the case of, the technology, method and apparatus should be considered as authorizing part for specification.

In the description of the invention, it is to be understood that the noun of locality such as " forward and backward, upper and lower, left and right ", " laterally, vertical, Vertically, orientation or position relationship indicated by level " and " top, bottom " etc. are normally based on orientation or position shown in the drawings and closed System, it is for only for ease of the description present invention and simplifies description, in the case where not making opposite explanation, these nouns of locality do not indicate that There must be specific orientation with the device or element for implying meaning or with specific azimuth configuration and operation, therefore can not manage Solve as limiting the scope of the invention；The noun of locality " inside and outside " refers to relative to inside and outside each part profile in itself.

In the description of the invention, it is to be understood that limit parts using the word such as " first ", " second ", only It is for only for ease of and corresponding parts is distinguished, does not such as have Stated otherwise, above-mentioned word does not have particular meaning, therefore not It is understood that as limiting the scope of the invention.

The present invention provides a kind of device for preparing microballoon.The device for preparing microballoon includes drop formation module, collects system Modeling block, motion module and control module.Drop formation module includes first fluid entrance, drop micro-fluidic chip and output end Mouthful, drop micro-fluidic chip includes runner system, and first fluid entrance and output port connect with runner system respectively, and drop is micro-fluidic Chip is used to the dispersed phase fluid from first fluid entrance entered in air stream enter runner system forming drop and exports drop from output port； Collecting manufacture module includes collecting manufacture main body, collects multiple collection holes that manufacture main body includes each having action face, respectively The action face for collecting hole is isolated from each other, and collects hole and drops to action face for reception liquid and drop shape is based in action face Into microballoon；Motion module and output port and/or collection manufacture main body drive connection, for being led in output port and collection manufacture Relative motion is produced between body so that each drop is accordingly dropped in the action face for collecting hole；Control module and drop formation mould Block coupling is to control drop formation module to generate drop, and control module is coupled with motion module to control motion module to act.

The drop for meeting Particle size requirements can be generated using drop formation module, and drop is accordingly instilled to different receipts It can prevent multiple orbicules from being influenced each other before microballoon prepares completion in collection hole；Microballoon is formed in action face, is advantageous to Control the shapes and sizes of microballoon.Therefore, each part of the device for preparing microballoon is maintained close ties with, is fitted to each other, and can make The standby microballoon for meeting Particle size requirements.The microballoon for meeting bioactivity requirement can also further be prepared.This prepares the device of microballoon It is adapted to the preparation of various microballoons, the microsize that is particularly suitable for use in and/or needs the preparation of microballoon for possessing bioactivity, for example, it is suitable Close the microballoon for preparing biological prepared Chinese ink.

Further, drop formation module and motion module are controlled by control module, this is prepared microballoon Device has higher automatization level, and control accuracy and preparation efficiency are higher so that each drop of micro-fluidic module generation It can be added drop-wise in different collection holes, have very high operation horizontal without operating personnel.

Because the action face in each collection hole for collecting manufacture main body is isolated from each other, it can ensure prepared by each microballoon The independence of journey.Relative to preparing the situations of multiple microballoons in same collection hole simultaneously, due to each microballoon preparation no longer Interfere, therefore can ensure that the performance of each microballoon is not influenceed by other microballoons.Collecting manufacture main body specifically can be with Orifice plate is manufactured to collect.

Wherein, the orbicule alleged by the present invention, it is in the transition structure of microballoon of collecting each stage in hole and micro- The general name of ball in itself, the wherein transition structure of microballoon for example including core liquid drop, core liquid drop solidification after formed microballon, The uncured of random layer clad or the chondritic by solidified forming are coated with core liquid drop or microballon.Separately Outside, for the shape of orbicule, orbicule refers not only to spheroid, also including spheroid, can also include close to spheroid or ellipsoid Other globoids of body.

Alternatively, runner system includes folder stream focus type runner or T-shaped runner.Folder stream focus type runner or T-shaped runner are beneficial to The size of drop, the regulation of generating rate, it is additionally favorable for the damage to the active material in drop during reduction generation drop.

Alternatively, micro-fluidic chip includes two or more runner system；And/or drop formation module includes two or more the One fluid intake；And/or drop formation module includes two or more output port；And/or drop formation module is including multiple Micro-fluidic chip.

The setting can improve the preparation efficiency of microballoon.For example, multigroup drop can be generated simultaneously by multiple runner systems To improve drop formation efficiency；Drip in multiple collection holes that main body can be manufactured to collecting simultaneously by multiple output ports Note.

The setting also improves the flexibility of microballoon preparation.Because each microballoon preparation process is separate, it is easy to pass through The difference to dripping quantity in each collection hole is controlled to be prepared while realizing that different-grain diameter is layered chondritic.Such as it can lead to Cross the different differences for realizing the dripping quantity to each collection hole of particle diameter for the drop for exporting different output ports.Even, may be used With by making the material of drop that drop caused by different runner systems and different output ports export different, or can lead to It is different to cross the material for the drop for exporting different drop micro-fluidic chips, different core liquid liquid is added dropwise in each collection hole Drop or covering liquid drop are prepared to realize while variety classes microballoon.Can also be by multiple micro-fluidic chips in generation core Covering liquid drop or curing agent drop are generated during core liquid drop simultaneously to improve preparation efficiency of layering chondritic etc..So as to So that the device for preparing microballoon of the present invention disclosure satisfy that preparation demand with a greater variety.

Alternatively, drop micro-fluidic chip is removably disposed.The drop that the setting is beneficial to change different model is micro-fluidic Chip is to change the particle diameter of microballoon and thickness of each layer etc. when microballoon is layering chondritic, beneficial to each portion of control microballoon The size and overall dimensions divided.

Alternatively, drop formation module also includes input block, and the runner system of input block and drop micro-fluidic chip connects Pass to the fluid conveyed to the runner system of drop micro-fluidic chip for forming drop.Input block for example connects including input Pipe, input preferably include input capillary communicating pipe.

Input block can be specifically divided into input block for inputting dispersed phase fluid and for inputting continuous phase fluid Input block.Dispersed phase fluid can be core liquid, covering liquid or curing agent etc..Continuous phase fluid and dispersed phase fluid not phase It is molten, can be liquid or gas.The drop of generation different materials can use identical continuous phase fluid, can also Using different dispersed phase fluids.

Drop formation module also includes pumping installations, and pumping installations connects with the runner system of drop micro-fluidic chip, pumping Device is used to pump the fluid for forming drop to the runner system of drop micro-fluidic chip.

Control module is coupled with pumping installations to control pumping device action.Control module couples with pumping installations to lead to Cross the generating rate and size droplet diameter of the control control drop to pumping installations.

Pumping installations can become one with drop micro-fluidic chip can also be with drop micro-fluidic chip split settings. Pumping installations becomes one with drop micro-fluidic chip can reduce the space hold for the device for preparing microballoon, and reduce outside Wiring etc..Pumping installations and drop micro-fluidic chip split settings are then more beneficial for replacing and the pumping dress of drop micro-fluidic chip The maintenance put.

Alternatively, the inner surface of the runner system in drop micro-fluidic chip is hydrophobic surface, it is therefore preferable to super-hydrophobicity Surface.

After drop contacts with the surface of solids, tangent line and the solid-liquid of the liquid-vapor interface by solid-liquid-gas three-phase point of intersection are handed over Angle between boundary line is contact angle, and contact angle is bigger, then the hydrophobicity of the surface of solids is stronger, and drop also is easier to form ball Body.According to the difference of contact angle, the surface of solids can be divided into hydrophilic surface and hydrophobic surface, hydrophobic surface includes super Hydrophobic surface.Wherein, hydrophilic surface refers to that contact angle is less than 90 ° of the surface of solids, when liquid instills hydrophilic surface, It can not be shaped to spherical, but " lying prone " is on a solid surface, in flat.Hydrophobic surface refers to that contact angle is more than 90 ° The surface of solids.Super hydrophobic surface then refers to that contact angle is more than 150 ° and the surface of solids of the roll angle less than 10 °.

It can be seen that when the surface of solids uses hydrophobic surface or super hydrophobic surface, the liquid, aqueous of the surface of solids is flowed through The resistance for the surface of solids being subject to is by less than the resistance of the surface of solids with non-hydrophobic property surface.Therefore, by runner system Surface is arranged to hydrophobic surface, it is therefore preferable to which super hydrophobic surface is beneficial to the resistance for reducing drop conveying.

It is preferably carried out at one in mode, the inner surface of the output port of drop formation module is hydrophobic surface, excellent Selection of land is super hydrophobic surface.

It can be seen from description more than to hydrophobic surface and super hydrophobic surface, the setting is it is possible to prevente effectively from drop pair Output port inner surface sticks so that titration process is easier to realize, improves titration efficiency and ooze effect, can prevent shape Into drop material in the unnecessary residual of output port and retardance.In addition, the setting smoothly exports beneficial to drop, and defeated Drop is closer to spherical when going out.

Alternatively, the flow area size adjustable of at least part runner of the runner system of drop micro-fluidic chip, which saves land, sets Put.

Pass through the regulation of the channel size of runner system, thus it is possible to vary the particle diameter of the drop of drop micro-fluidic chip generation.Can To prepare the drop compared with small particle by the way that channel size is diminished, such as available for generation meet that volume is less than tens pL levels Drop；The drop of greater particle size can also be prepared by the way that channel size is become into big, such as can be used for generating particle diameter and be more than 500 μm drop.

It is preferably carried out at one in mode, the action face collected in the collection hole of manufacture main body is hydrophobic surface, Preferably super hydrophobic surface.

It can be seen from description more than to hydrophobic surface and super hydrophobic surface, hydrophobic surface is dropped to when liquid, aqueous When upper, it was more easy to be shaped to orbicule.Therefore, the action face for collecting hole is arranged to hydrophobic surface, it is therefore preferable to super-hydrophobicity Surface be beneficial to control microballoon global shape be orbicule and layering chondritic each Rotating fields be orbicule.

Specifically, carried out using the hydrophobicity feature of action face to instilling the core liquid drop in collection hole at shaping Reason, makes core liquid drop be shaped to orbicule, when preparing single chondritic, can guarantee that the sphericity of microballoon.Divide preparing The sphericity of each layer such as core can then be ensured during layer chondritic；When preparing layering chondritic, covering liquid liquid is also allowed for Drop more uniformly coats to collecting orbicule molded in hole, and enables covering liquid spherical in hole to collecting Body is intactly coated, so as to ensure that each position of final obtained layering chondritic has more preferable sphericity in the lump.

It can be seen that relative in the prior art directly by the mixed solution of core liquid and covering liquid instill curing agent in and rely on Spontaneous in solidification process to chemically react to be molded the mode of microballoon, the present invention can realize forming shape and the shaping to microballoon Effective control of effect, ensure that microballoon has the standard between preferable sphericity and batch unified.

Collecting manufacture module also includes drainage structure, and drainage structure is used to discharge the residual liquid collected in hole.

Discharging residual liquid can be carried out after a certain transition structure of microballoon is completed, such as be solidified in core liquid drop And formed after core or certain layer of clad formed after carry out, can also microballoon prepare complete after carry out.

Drainage structure can be arranged in collection manufacture main body.Now, it is compact to collect manufacture modular structure, structurally and operationally It is relatively easy.

Drainage structure can also include discharge opeing main body, and discharge opeing main body includes multiple collection holes, multiple collections of discharge opeing main body Residual liquid is discharged after receiving the material in the multiple collection holes for collecting manufacture main body in hole.Discharge opeing, row are carried out using discharge opeing main body Except preparation of the process on microballoon of residual liquid influence it is relatively small.Discharge opeing main body is, for example, discharge opeing orifice plate.

Drainage structure includes being arranged on the bottom wall in the collection hole for collecting manufacture main body or discharge opeing main body and/or in side wall Outage.Residual liquid is excluded using outage, draining mode is relatively simple, and outage is easy to process.

In one embodiment, drainage structure also includes the closeouts blocked to outage, closeouts and discharge opeing Hole is detachably connected.Closeouts are set to prevent that having in hole will be collected when being not required to discharge and collecting the residual liquid in hole Misprinted out with material.

Alternatively, in the case where outage is arranged at the side wall for collecting hole, drainage structure also includes tilting gearing, tilts Device collects hole towards the side wall side inclination provided with outage when the residual liquid in hole is collected in discharge for controlling.Tilt The residual liquid discharge that the setting of device is beneficial to collect in hole.

Control module is coupled with tilting gearing to control tilting gearing to act.The automatic, smart of tilting gearing is realized in the setting Really control.

It is preferably carried out at one in mode, drainage structure can also include vacuum suction apparatus, and vacuum suction apparatus is used Residual liquid in by outage collected at suction hole.

Vacuum collection device can with collect manufacture main body on outage be used cooperatively, can also with discharge opeing main body Outage is used cooperatively.Can be in favor of the residual liquid emptying in collection hole using vacuum suction apparatus.

Alternatively, collecting manufacture module can also include rocking generation device, rock generation device and be used to manufacture collection Main body generation makes rocking for the material balling-up in collection hole.

Generation device is rocked in setting can improve the shape of microballoon, when microballoon is is layered chondritic, beneficial to each layer bag The uniform cladding of coating；Further, since the shaping of orbicule can be accelerated, the preparation efficiency of microballoon can be improved.

Control module with rock generation device couple with control rock generation device action.The setting, which is realized, rocks generation dress Automatic, the accurate control put.

Additionally preferably, manufacture main body is collected to be removably disposed.The setting, which is beneficial to change, collects manufacture main body, Ke Yi Drop is instiled and collected and the collection manufacture main body of completing corresponding drop will have been collected when completing moves at it the other preparations of continuation Step, new collection manufacture main body is replaced with, starts the preparation work of the orbicule of a new round, improves the preparation efficiency of microballoon； Furthermore it is also possible to according to the quantity and particle diameter of the microballoon of required preparation, selection is with the suitable receipts for collecting hole number and size Collection manufacture main body.

Motion module can include chip motion device, and chip motion device is used to control drop micro-fluidic chip to move, The output port of drop formation module is synchronized with the movement with micro-fluidic chip, and control module is coupled with chip motion device to control core Piece telecontrol equipment acts.For example, chip motion device includes being used to control the core that drop micro-fluidic chip moves in the horizontal plane Piece horizontal movement component and/or the Chip Vertical moving parts for controlling drop micro-fluidic chip to move along the vertical direction.

Motion module can also include bulk motion device, and bulk motion device, which is used to control, collects manufacture bulk motion, Control module is coupled with bulk motion device to control bulk motion device action.For example, bulk motion device includes being used to control The main body horizontal movement component and/or collect manufacture main body vertically for controlling that system collection manufacture main body is moved in the horizontal plane The body normal moving parts of direction motion.

Drop formation module also includes output block, and the entrance of output block connects with the runner system of drop micro-fluidic chip Logical, the outlet of output block forms the output port of drop formation module.For example including exporting communicating pipe, output connects output block Siphunculus preferably includes output capillary.

Motion module can also include the output block telecontrol equipment for being used to control the position of the outlet of output block.Pass through Output block telecontrol equipment can realize that drop instills in different collection holes one by one.

Certainly, drive the motion for collecting manufacture main body progress that drop can be met in multiple collection holes in bulk motion device In distribution requirements in the case of, the outlet of output block can be fixedly installed.

Additionally preferably, preparing the device of microballoon also includes reagent memory module, and reagent memory module is used for for storage Form the material of microballoon.Material for forming microballoon can both include such as core liquid or covering liquid main material, can also include Such as curing agent, continuous phase fluid or cleaning fluid auxiliary material.

For example, reagent memory module can include：Core liquid memory space；And/or covering liquid memory space；And/or Curing agent memory space；And/or cleaning fluid memory space；And/or continuous phase fluid memory space.

Wherein, core liquid memory space is used to store core liquid, and core liquid is the constituent of the core of composition microballoon Material；Covering liquid memory space is used to store covering liquid, and covering liquid is coated on the bag on the outside of the orbicule collected in hole for composition The material of coating；Curing agent memory space is used to store curing agent, and curing agent collects the material of the orbicule in hole for solidification；Clearly Washing lotion memory space is used to store cleaning fluid, and cleaning fluid collects the material of the orbicule in hole for cleaning；Continuous phase fluid stores Space is used to store continuous phase fluid, and continuous phase fluid is that dispersed phase fluid is divided into drop in drop micro-fluidic chip Material.

Wherein, the quantity of various memory spaces is not limited to one, and the quantity of every kind of memory space is equal in case of need There can be two or more.

For example, if the quantity demand of certain material is larger, two or more memory space can be used to store material of the same race Material.

For another example in layering chondritic of the manufacture with more than two layers clad, the material of more than two layers clad Can be with identical, can also be different.If the material of more than two layers clad is formed by two or more covering liquids, covering liquid storage The quantity in space can be two or more, and each covering liquid memory space can store different types of covering liquid.

For another example when core has more than two layers core layer, if more than two layers core layer is by two or more core liquid Formed, then the quantity of core liquid memory space can be two or more, and each core liquid memory space can store different types of Core liquid.

For another example when being solidified to core and clad using curing agent, if necessary to use different curing agent, solidification The quantity of agent memory space can be two or more, and each curing agent memory space can store different types of curing agent.

For another example if at least both are micro-fluidic using drop in core liquid drop, covering liquid drop or curing agent drop Chip is generated or every kind of drop is formed using different materials, when using different continuous phase fluids if desired, continuous phase Fluid reservoir is it can also be provided that two or more, each continuous phase fluid memory space store different types of continuous phase stream Body.

First fluid entrance with core liquid memory space there is connected state to make drop micro-fluidic chip be used to generate core Liquid drop, control module control each core liquid drop accordingly to drop in the action face for collecting hole；And/or first fluid enters Mouth with covering liquid memory space there is connected state to make drop micro-fluidic chip runner system be used to generate covering liquid drop, control mould Block also controls each covering liquid drop accordingly to drop in the action face for collecting hole；And/or first fluid entrance is deposited with curing agent There is connected state to make drop micro-fluidic chip runner system be used to generate curing agent drop in storage space, and control module controls each solidification Agent drop is accordingly dropped in the action face for collecting hole.

The setting of connected relation between first fluid entrance and different memory spaces, the micro-fluidic core of drop can be passed through Piece can generate core liquid drop, and can generation covering liquid drop and/or curing agent drop, and microballoon is prepared so as to reduce The core component of device.

Certainly, can also be micro-fluidic with the different drop of the drop micro-fluidic chip from generating core liquid drop in the present invention Chip generates covering liquid drop and/or curing agent drop, or using liquid relief module generation covering liquid drop and/or curing agent liquid Drop.

Preparing the device of microballoon also includes the first temperature control module, and the first temperature control module is used to control core liquid, covering liquid, consolidated The temperature of at least one of agent, cleaning fluid and continuous phase fluid.The setting be beneficial to the physicochemical property for ensureing each material and The physical behavior, chemical property etc. of each material is adjusted using temperature change, is particularly advantageous for ensureing the bioactivity of microballoon.

Preferably, the first temperature control module includes multiple material structure of controlling temperature independent of each other, multiple material structure of controlling temperature bags Include for control the temperature of core liquid core liquid structure of controlling temperature, the covering liquid structure of controlling temperature of temperature for controlling covering liquid, The cleaning fluid structure of controlling temperature and use of curing agent structure of controlling temperature for the temperature that controls curing agent, the temperature for controlling cleaning fluid In at least one continuous phase fluid structure of controlling temperature of temperature of control continuous phase fluid.The setting can realize various material temperatures Independent control.

Control module is coupled with the first temperature control module to control the first temperature control module to act.Each material temperature is realized in the setting Automatic, accurate control.

Additionally optionally, preparing the device of microballoon also includes the second temperature control module, and the second temperature control module, which is used to control, to be collected The temperature of material in hole.The temperature that the material in hole is collected in control is beneficial to the physicochemical property that the material in hole is collected in control, The orbicule collected in hole can also be solidified by collecting when the orbicule in hole includes temperature sensing material.

The second temperature control module is set to solidify without using curing agent to some structure sheafs of microballoon or microballoon, and Solidification is directly realized by way of the temperature for controlling orbicule.The curing mode is simple and easy, can reduce and use curing agent band The adverse effect come, such as the influence to the bioactivity of microballoon can be reduced.

Control module is coupled with the second temperature control module to control the second temperature control module to act.Solidification temperature is realized in the setting Automatically, accurate control.

Alternatively, liquid relief module can also be included by preparing the device of microballoon, and liquid relief module is used for instil covering liquid, curing agent At least one of with cleaning fluid.The preparation efficiency of microballoon can be improved using liquid relief module.

Additionally preferably, in order that core liquid and/or covering liquid are preferably coated on orbicule, of the invention preparing is micro- The device of ball can also include pretreatment module, and the pretreatment module is used to carry out core liquid and/or covering liquid The pretreatment that core liquid and/or covering liquid can be made to be combined with collecting orbicule molded in hole.

By the pretreatment of pretreatment module, core liquid and/or covering liquid can preferably be incorporated into and collect in hole Molded vesicle surface, clad is formed beneficial to cladding is carried out to orbicule.The knot of core liquid or covering liquid and orbicule Close, can be by making core liquid or covering liquid be realized with the mode such as opposite charges on orbicule band.

As a kind of embodiment of pretreatment module, pretreatment module can be by making core liquid or cladding Liquid with collecting in hole opposite charges on molded orbicule band, such core liquid and/or covering liquid can opposite charges it Between be adsorbed on orbicule in the presence of mutual attractive force, it is simple in construction, and be easily achieved.

Present invention also offers the method for preparing microballoon.The method for preparing microballoon mainly includes：Core liquid drop formation And collection step, including：Core liquid is passed through into drop micro-fluidic chip to generate core liquid liquid by drop micro-fluidic chip Drop；Core liquid drop is accordingly dropped in the action face in the different collection holes for collecting manufacture main body；Microballoon generation step, Including：Core liquid droplet formation microballoon is based in the action face for collecting hole.

Core liquid drop is generated using drop micro-fluidic chip, vibrated without applying to core liquid, to the performance of core liquid Influence is smaller, therefore can effectively solve the problem that in the prior art using the infringement microballoon caused by vibration or impulse method progress liquid separation The problem of energy, particularly with core liquid of the inside containing cell, the infringement to cytoactive can be significantly reduced, meet that biology is beaten Requirement of the print field to the bioactivity of microballoon.And the smaller microballoon of particle diameter can be made, biometric print field can be met Requirement to microspherulite diameter.And the precision of each dripping quantity can be more accurately controlled, effectively reduces scale error, can Enough coherence requests met to microspherulite diameter, it also disclosure satisfy that the otherness requirement to microspherulite diameter.

Core liquid drop formation and collection step also include：Continuous phase fluid is passed through into drop micro-fluidic chip so that even Continuous phase fluid separates core liquid in the runner system of micro-fluidic chip and generates core liquid drop, continuous phase fluid and core liquid not phase It is molten.

Continuous phase fluid can be gas or liquid.But more preferably gas, when connection phase fluid is gas, Ke Yiwu The separating step of continuous phase and drop need to be set, or cleaning or the discharge step of continuous phase fluid need not be set, thus be beneficial to carry The preparation efficiency of high microballoon, reduce processing step when prepared by microscopic, spherical body.

Core liquid includes the material for being molded core liquid by external action.External action includes temperature control effect, changed Effect and/or biological respinse effect.For example, when core liquid includes temperature sensing material, because temperature sensing material can be in certain temperature Lower solidification or liquefaction, therefore so that core liquid drop can by way of controlling temperature solidified forming.For another example core liquid Including can be molded by chemical action material when, can by the way of curing agent solidified forming.Curing molding makes core Intensity strengthened, also protected the bioactivity of core.

Microballoon generation step includes clad generation step, and clad generation step includes：Covering liquid drop formation and receipts Collect step, including generation covering liquid drop, and covering liquid drop is accordingly dropped in the action face in different collection holes, bag Covering liquid is coated on the material of the clad on the outside of the orbicule collected in hole for composition；Encapsulation steps, including make to drop to effect table Covering liquid drop on face is coated on the outside of the orbicule collected in hole to form clad.

Clad generation step can form the microballoon with layering chondritic, and clad can be formed to core and protected Shield, strengthens the bulk strength of microballoon, is protected the bioactivity of core.

It is alternatively possible to covering liquid drop is generated by drop micro-fluidic chip；Or generated and coated by liquid relief module Liquid drop.

Covering liquid drop is generated using drop micro-fluidic chip, vibrated without applying to covering liquid, to the performance of covering liquid Influence is smaller, therefore can effectively solve the problem that in the prior art using the infringement microballoon caused by vibration or impulse method progress liquid separation The problem of energy.And the smaller microballoon of particle diameter can be made, requirement of the biometric print field to microspherulite diameter can be met.And The precision of each dripping quantity can be more accurately controlled, effectively reduces scale error, one to microspherulite diameter can either be met Cause property requires, also disclosure satisfy that the otherness requirement to microspherulite diameter.Generating covering liquid drop by liquid relief module can then carry The preparation efficiency of high microballoon.

The dripping quantity (volume or particle diameter that show as covering liquid drop) of covering liquid can pass through when generating covering liquid drop The mode precalculated determines, to realize the quantitative titration on demand to covering liquid.Specifically, can according to core volume, The dripping quantity of covering liquid is estimated and determined in advance to the parameter such as thickness and the quantity of electric charge, make it that the dripping quantity of covering liquid is just full Sufficient requirement.

But as a kind of alternative embodiments, excessive covering liquid first can also be instilled into collection hole, led to again afterwards Cross extraction raffinate and remove the residual liquid discharge that step will be collected in hole.So it is possible to prevente effectively from because of the volume of core, thickness and electricity The drop of identified covering liquid caused by the parameters such as lotus amount are not easy to determine or identified parameter easily has the reasons such as deviation The problem of dosage is still inaccurate, ensure that covering liquid dripping quantity disclosure satisfy that requirement.

Alternatively, encapsulation steps also include shaking step, shaking step is included in form clad during rock receipts Collection manufacture main body is so that collection manufacture main body generation makes rocking for the material balling-up in collection hole.

Shaking step can improve the shape of microballoon, beneficial to the uniform cladding of each layer clad；Further, since it can accelerate Orbicule shapes, and can improve the preparation efficiency of microballoon.

Microballoon generation step includes performing clad generation step at least twice.Clad generation step is performed at least twice At least two layers of clad can be formed.At least two layers of clad can be formed to core more effectively protects, and strengthens the whole of microballoon Body intensity, the bioactivity of core is set to be guaranteed.Furthermore it is possible to made by setting the clad of at least two layers different materials Different layers clad has different property, so that the performance of microballoon conforms better to design requirement.

Covering liquid includes the material for being molded covering liquid by external action.External action includes temperature control effect, changed Effect and/or biological respinse effect.For example, when covering liquid includes temperature sensing material so that covering liquid drop can be outside core The clad of solidification is formed by way of controlling temperature.For another example covering liquid includes the material that can be molded by chemical action During material, the clad of solidification can be formed by the way of curing agent.The clad of solidification can make microballoon more stable, make core The intensity of core is further strengthened, and is also further ensured that the bioactivity of core.

Preferably, microballoon generation step includes curing schedule, and curing schedule includes consolidating to collecting the orbicule in hole Change is handled.Wherein orbicule for example can be core liquid drop；It can also be core (including the core liquid drop without solidification Or the microballon that is formed after the solidification of core liquid drop) and one or more layers clad combining structure, remove outermost in the combining structure Any one layer of clad outside layer clad can be the clad without curing process or Jing Guo curing process, and outermost layer Clad is the clad without curing process.

Relative to prior art, the curing mode of the method for preparing microballoon of the invention is more flexible.Moreover, curing schedule Can be used for carrying out curing process to core and/or clad, certain layer can be directed to or some layers individually be solidified, beneficial to pair The state of each layer of microballoon is flexibly controlled.Because the core after solidification and the liquid fluidity of clad are weakened, because This can so make the core of cured processing and/or clad more stable, can also be further ensured that core and clad Molding effect.

Alternatively, curing process solidifies including the use of curing agent collects orbicule in hole, and curing agent is collected in hole for solidification Orbicule material；And/or curing process includes the temperature of control orbicule.

In the case where using curing agent solidification orbicule, in terms of existing technologies, this is prepared in the method for microballoon Curing agent is the solidification of the orbicule to having been formed, and therefore, the sphericity of the orbicule after solidified forming is also guaranteed.

In the case where carrying out curing process by temperature, because curing process can be by controlling the temperature of orbicule to enter OK, the shaping of core and/or clad can be no longer dependent on chemical reaction, therefore, it is possible to effectively expand available core liquid And/or the range of choice of covering liquid so that microballoon preparation by core liquid and/or covering liquid self-formed shaping performance limited It is relative to reduce, beneficial to the development of the technical fields such as biometric print.

When performing curing process to core and performing curing process to clad, the temperature of curing process may be controlled to 20-40 ° (being preferably controlled to 37 °), hardening time can be set as 5-180 minutes, and (hardening time can need according to material Select, be preferably set to 30 minutes in the range of being somebody's turn to do).Under the conditions of the curing process, the core after preferably solidification can be obtained And clad, and can ensure that the cell in core has preferable bioactivity.

It should be noted that solidifying orbicule even with curing agent, the temperature of orbicule can also be carried out simultaneously Control, in favor of ensureing the physicochemical property of orbicule, especially ensure the bioactivity of orbicule.

Solidifying structure to be solidified using curing agent includes：Curing agent drop is generated, and curing agent drop is accordingly dropped to The orbicule in hole is collected in the action face in different collection holes with solidification.

Alternatively, curing agent drop is generated by drop micro-fluidic chip；Or curing agent liquid is generated by liquid relief module Drop.Generating curing agent drop by drop micro-fluidic chip can make the dosage of curing agent drop more accurate；Pass through liquid relief mould Block generation curing agent drop can also improve the generation of curing agent drop and efficiency is added dropwise.

Alternatively, microballoon generation step includes extraction raffinate removing step, and extraction raffinate removing step is collected residual in hole including removing Extraction raffinate body.Cleaning step is beneficial to remove the excess stock in microballoon generating process and after the completion of the preparation of microscopic, spherical body.

Preferably, extraction raffinate, which removes step, includes cleaning step, and cleaning step includes cleaning fluid and shape is added dropwise into collection hole Into residual liquid.

Using cleaning fluid in addition to it can make excess stock and remove totally, the unnecessary bag after forming clad can also be removed Unnecessary charge species in covering liquid or other liquid, to avoid unnecessary charged liquid from forming heterogeneous texture in vesicle surface Or bulge-structure, influence to be layered the forming shape and physicochemical property of chondritic.Do not combined again by cleaning fluid and with orbicule Remaining covering liquid is expelled to together to be collected outside hole.

Preferably, extraction raffinate removes step and includes being sucked by vacuum to collecting the residual liquid in hole.Vacuum suction will be residual Remaining fluid removal obtains more complete.

Preparing the method for microballoon also includes material temperature rate-determining steps, material temperature rate-determining steps include control core liquid, The temperature of at least one of covering liquid, curing agent, cleaning fluid and continuous phase fluid.The setting is beneficial to keep microballoon and its preparation The physicochemical property of material, such as beneficial to the bioactivity for keeping the microballoon with cell.

Alternatively, prepare be layered chondritic in the case of, in order that covering liquid be more easily coated on it is to be covered Orbicule on, the method for preparing microballoon can also include pretreatment step, and the pretreatment step is to core liquid And/or covering liquid progress can make the pretreatment that core liquid and/or covering liquid are combined with collecting orbicule molded in hole.

The pretreatment step enable instillation core liquid and/or covering liquid preferably with collect hole in it is molded Orbicule combines.In pretreatment step, core liquid and/or covering liquid can be allowed with collecting orbicule molded in hole Take different electric charges enable core liquid and/or covering liquid using electrostatic adsorption with it is molded spherical in collection hole Body is bonded to each other.

In order to further improve Electrostatic Absorption effect, in the pretreatment step, in addition to core liquid and/or bag The step of pH value of covering liquid is adjusted.By the way that the pH value of core liquid or covering liquid is adjusted, can cause core liquid or The electric charge of participation Electrostatic Absorption is more in covering liquid, and the reaction of Electrostatic Absorption is more violent, and core liquid or covering liquid are to whole ball The cladding of shape body is more abundant.Such as the pH value of core liquid and/or covering liquid can be adjusted to 6-10,7.6 are preferably adjusted to, Under the conditions of the pH value, wrap participated in celliferous collagen solution electrostatical binding the quantity of electric charge it is more, and the reaction of electrostatical binding It is more violent, so as to obtain more preferable Electrostatic Absorption effect.

Certainly, destatic outside suction type, the pre-treatment step can also make core liquid or cladding using other modes Liquid is bonded to each other with collecting molded orbicule in hole, combination herein can be core liquid or covering liquid total material with Collect molded orbicule in hole be combined or core liquid or covering liquid in moieties with collect Kong Zhongyi into The orbicule of type is combined.

Alternatively, core liquid drop formation and collection step are performed at least twice.

Microballoon can be single chondritic or layering chondritic.

It can have individual layer core and the layering chondritic of individual layer clad to be layered chondritic, in this case, It is orbicule that core liquid drop is separately formed in the presence of action face, forms individual layer core；And in clad generation step In, covering liquid wraps to the core (core of individual layer as collects orbicule molded in hole in such cases) of individual layer Cover, form individual layer clad, and ultimately form the layering chondritic with individual layer core and individual layer clad.

Layering chondritic can also be the layering chondritic with multilayer core, and this kind of layering chondritic has extremely Few two layers of core, in this case, can be on the basis of the molded orbicule by core liquid droplet formation in collecting hole The core liquid drop that core liquid drop is added dropwise again and makes newly to be added dropwise is new orbicule with molded orbicule connecting shaping, from And two layers of core layer is formed, by that analogy, the core with multilayer core layer can be formed.

Similarly, the layering chondritic with multilayer coating structure layer can also be prepared, this kind of layering chondritic has extremely Few two layers of clad, in this case, in the preparation process of microballoon, re-cover clad generation step, the object of covering liquid cladding (namely collecting orbicule molded in hole) can be core or the mistake of the molded microballoon with least one layer of clad Cross structure.

For the microballoon with least two layers core, wherein each layer core can be by identical or different core liquid shape Into；Similarly, for the microballoon with least two layers clad, wherein each layer clad can be by identical or different bag Covering liquid is formed.

It can be seen that the method for preparing microballoon of the invention, can not only prepare not stratified single chondritic, and can The layering chondritic with individual layer core and individual layer clad is prepared, but also can be prepared with multilayer core and/or more The layering chondritic of layer clad, so as to meet the needs of all kinds of layering chondritics.

For example, the spherical knot of layering with one layer of core and three layers of clad can be prepared based on the method for preparing microballoon Structure.One layer of core is the celliferous collagen solution of bag.Three layers of clad are respectively to be coated on core periphery and from inside to outside successively Polylysine layer, sodium alginate layer and the polylysine layer of arrangement.Wherein, the electric charge of collagen solution institute band and polylysine layer institute The opposite charge of band, the opposite charge of sodium alginate layer and polylysine layer institute band, to ensure the mutual absorption between each layer.

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

The microballoon prepared by the present invention can be used for multiple fields, such as biometric print (such as 3D biometric prints), tissue work The fields such as journey, regenerative medicine.

For example, microballoon can be layering chondritic, it, which is formed, can include at least the one of one layer of core and encapsulation core Layer clad.Core includes cell, and cell can be grown, bred, broken up or be migrated, the material in core liquid beyond cell It is made up of Biodegradable material, and required material 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.

In some preferred embodiments, the device for preparing microballoon of the invention and prepare prepared by the method for microballoon Microballoon is solid or semisolid.In other some preferred embodiments, the device for preparing microballoon of the invention and prepare it is micro- Microballoon prepared by the method for ball is gel state, for example, the core of the layering chondritic prepared and/or clad can be solidifying Colloidal state.In some preferred embodiments, prepared layering chondritic includes hydrogel.In some preferable embodiment party In formula, hydrogel includes alginate, agarose, gelatin, chitosan or other water-soluble or hydrophilic polymers.

Various embodiments of the present invention will be described in detail below.

First embodiment

First embodiment gives a specific embodiment of the device for preparing microballoon of the present invention.Fig. 1 to Fig. 9 is shown The structure and principle of first embodiment of the invention and its part variation.

As shown in figure 1, the device for preparing microballoon of first embodiment includes drop formation module 1, collection manufactures module 2, Motion module 3, control module 4, reagent memory module 5, the first temperature control module (not shown), the second temperature control module 6, material are located in advance Manage module and pedestal 10.

Drop formation module 1, collect manufacture module 2, motion module 3, reagent memory module 5, the first temperature control module and the Two temperature control modules 6 may be contained within pedestal 10.

Specifically, pedestal 10 includes base station 101 and is connected with base station 101 and is arranged at the support frame of the top of base station 101 102。

Drop formation module 1 is arranged on support frame 102.Collect manufacture module 2 and base station is arranged on by motion module 3 On 101.The temperature control module 6 of reagent memory module 5 and second may be contained within base station 101.

In the present embodiment, control module 4 is separately provided, such as on the console that can be arranged at outside pedestal 10.Certainly, exist In other unshowned embodiments, control module 4 can also be arranged on pedestal 10.

As shown in Fig. 2 drop formation module 1 mainly includes drop micro-fluidic chip 11, pumping installations 12, input block 13 With output block 14.In the present embodiment, input block 13 is in particular to input capillary.Defeated portion's part 14 is in particular to export hair Tubule.

Control module 4 is coupled with drop formation module 1 to control the action of drop formation module 1, so as to control drop Generating rate, particle diameter etc..

Drop formation module 1 includes first fluid entrance, second fluid entrance and output port.Drop micro-fluidic chip 11 Including the runner system 111 for forming drop.First fluid entrance, second fluid entrance and output port respectively with runner system 111 connections.First fluid entrance is used to input dispersed phase fluid to drop micro-fluidic chip 11.Dispersed phase fluid is to form drop Constituent material.Second fluid entrance is used to input continuous phase fluid to drop micro-fluidic chip 11.Output port is used In the drop formed in delivery channel system 111.

As shown in figure 3, in the present embodiment, drop micro-fluidic chip 11 is first-class including being connected respectively with runner system 111 Road system entrance 1111, second flow channel system entrance 1112 and runner system outlet 1113.

In the present embodiment, drop formation module 1 includes being used to convey the input block 13 of dispersed phase, for conveying continuous phase Input block 13 and output block 14.Pumping installations 12 pumps corresponding fluids by way of being pressed to memory space.Therefore, The entrance for conveying the input block 13 of dispersed phase forms first fluid entrance, and the first fluid entrance passes through first flow system entrance 1111 connect with runner system 111.The entrance for conveying the input block 13 of continuous phase forms second fluid entrance, and the second fluid enters Mouth is connected by second flow channel system entrance 1112 with runner system 111.The entrance of output block 14 by runner system outlet 1113 with The connection of runner system 111, the outlet of output block form the output port of drop formation module 1.

Certainly, in other embodiments, if directly drawing dispersed phase fluid by pumping installations, the pumping installations Drawing the entrance of dispersed phase fluid then turns into the first fluid entrance of drop formation module.Similarly, if pumping installations is directly inhaled Continuous phase fluid is taken, then the entrance of the absorption continuous phase fluid of the pumping installations enters as the second fluid of drop formation module Mouthful.If drop formation module 1 does not include output block directly exports drop from runner system outlet 1113, now runner system goes out Mouth 1113 forms output ports.

Drop micro-fluidic chip 11 can be used for forming the various drops prepared needed for microballoon, wherein, it is primarily used to form Core liquid drop, can be used for forming covering liquid drop, can be also used for forming curing agent drop.

Drop micro-fluidic chip refers to the micro-fluidic chip with drop formation function.The micro-fluidic chip of the present embodiment Principle is that two kinds of immiscible fluids are passed through in the runner system of micro-fluidic chip, and continuous phase is used as by the use of one of which fluid Another fluid as dispersed phase fluid of fluid partitioning, makes dispersed phase fluid be divided into drop.

Specifically, continuous phase fluid and dispersed phase fluid respectively enter the different runners of the runner system of drop micro-fluidic chip Afterwards, the interface of continuous phase fluid and dispersed phase fluid can be formed in the intersection of different runners.Dispersed phase fluid pushes away external force Synchronously travelled forward with continuous phase fluid in the presence of the dynamic and shearing force of continuous phase fluid.When interface interfacial tension not When being enough the shearing force for maintaining continuous phase fluid to be applied to dispersed phase fluid, dispersed phase fluid fracture generation is independent by continuous phase The micro volume unit that fluid surrounds is drop.

For example, continuous phase fluid be oil and in the case that dispersed phase fluid is water, form oil/water circle in profit intersection Face, aqueous phase synchronously travels forward in the presence of the promotion of external force and oil phase shearing force with oil phase, when the boundary of oil/water interface Face tension force is not enough to maintain oil phase when being applied to the shearing force of aqueous phase, the independent drop surrounded by oil phase of aqueous phase fracture generation.

As shown in figure 3, drop micro-fluidic chip 11 includes being used for the runner system 111 for forming drop.

As shown in Figures 2 and 3, in the first embodiment, runner system 111 includes folder stream focus type runner.Folder stream focus type Runner includes first flow 111A and be symmetricly set in first flow 111A both sides and connected with first flow 111A two the Two runner 111B.Dispersed phase fluid is passed through to first flow 111A by first flow system entrance 1111.Pass through second flow channel system Entrance 1112 is passed through continuous phase fluid to second flow channel 111B.Continuous phase fluid is located at intersection 111C by first flow 111A's Dispersed phase fluid in the flow channel section of upstream is divided into drop in first flow 111A and second flow channel 111B intersection 111C, Drop after separation flows through the defeated through the outlet 1113 of runner system after the flow channel section in intersection 111C downstreams of first flow 111A Go out.

First flow 111A is straight channel in the folder stream focus type runner of first embodiment, and two second flow channel 111B are symmetrical Ground and the both sides that first flow 111A is angularly arranged at first flow 111A, second flow channel 111B with it is first-class When angle between road 111A is 90 °, folder stream focus type runner shows as cross runner.

With reference to figure 4, solid arrow represents continuous phase fluid in Fig. 4, and dotted arrow represents dispersed phase fluid.It is poly- with folder stream The operation principle of the drop micro-fluidic chip generation drop of burnt type runner is as follows：Dispersed phase fluid (corresponds to the from intermediate flow channel One runner) flow into, continuous phase fluid flows into from two side runners (corresponding to second flow channel) of intermediate flow channel, in intermediate flow channel and two The intersection continuous phase fluid of side runner produces the effect that folder stream focuses on to dispersed phase fluid, and dispersed phase fluid is continuous by both sides The effect of the symmetrical shearing force of phase fluid and be separated into drop.

In an alternate embodiment of first embodiment, runner system can include T-shaped runner.T-shaped runner includes the 3rd Runner and the 4th runner that third flow channel is intersected at third flow channel.Third flow channel is used to be passed through continuous phase fluid, continuous phase stream Dispersed phase fluid is divided into drop by body in the intersection of third flow channel and the 4th runner.4th runner is used to be passed through dispersed phase stream Body.

Referring to Fig. 5, solid arrow represents continuous phase fluid in Fig. 5, and dotted arrow represents dispersed phase fluid.With T-shaped stream The operation principle of the drop micro-fluidic chip generation drop in road is as follows：Horizontal run (corresponds to continuous phase fluid from figure respectively Third flow channel) flow into, dispersed phase fluid flows 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), dispersed phase fluid is acted on by the shearing force of continuous phase fluid, at two-phase interface Interfacial tension when being insufficiently resistant to continuous phase fluid and being applied to the shearing force of dispersed phase fluid, dispersed phase fluid fracture generation is only The vertical micro volume unit by continuous phase fluid cladding is drop.

Wherein, the runner system with folder stream focus type runner generates drop more compared with the runner system with T-shaped runner Stable, the particle size controlled range of the drop of generation is wider.And T-shaped runner then has simpler structure.

In first embodiment preferably, the inner surface of the runner system 111 in drop micro-fluidic chip 11 is super hydrophobic surface, With hydrophobicity.Specifically, the first flow 111A flow channel section positioned at intersection 111C upstream and downstreams, two second flow channels 111B and intersection 111C etc. inner surface is respectively provided with hydrophobicity.When this is arranged on generation water-containing drop, runner can be weakened It is adhesion of the inner surface to drop, reduces flow resistance.

There is the inner surface of runner system 111 hydrophobic drop micro-fluidic chip 11 to be mainly used in generating water-containing drop.This Kind micro-fluidic chip 11 can be used and made using dimethyl silicone polymer (PDMS, polydimethylsiloxane), and right The inner surface of the runner system of drop micro-fluidic chip, which carries out hydrophobic treatment, makes the inner surface of the runner system of drop micro-fluidic chip be in Existing hydrophobicity.Glass (Glass) or polymethyl methacrylate (PMMA, polymethyl can also be used Methacrylate drop micro-fluidic chip) is made, and carry out hydrophobic treatment to runner system inner surface to make drop micro-fluidic chip Runner system inner surface present hydrophobicity.The mode that hydrophobic treatment is carried out to runner system inner surface is, for example, to pass through octadecyl Trichlorosilane (OTS, octadecyltrichlorosilane) is surface-treated.

In addition, in order to solve the problems, such as that heavy viscous material is difficult to hanging drop, it is preferable that the output end of drop formation module 1 The inner surface of mouth is hydrophobic surface, it is therefore preferable to super hydrophobic surface.As it was previously stated, drop formation module 1 in the present embodiment Output port be drop formation module 1 output block 14 outlet.In the present embodiment, the output end of drop formation module 1 Mouth is set with being relatively fixed with drop micro-fluidic chip 11.

There is the inner surface of output port hydrophobicity drop output can be made smooth, avoid droplets from material at output port Residual, and beneficial to output drop closer to spherical.

In first embodiment, drop micro-fluidic chip 11 is removably disposed.Drop micro-fluidic chip 11 is detachable, can be with Difference in functionality, the drop micro-fluidic chip of different scales are configured,

Meet that different drops prepares demand.For preparing the microballoon with layering chondritic, profit is also helped Other drops in addition to core liquid drop are formed with drop micro-fluidic chip, such as clad drop and curing agent drop, from And beneficial to the microballoon that microballoon or solidified forming with one or more layers clad are prepared using multiple material.

In first embodiment, drop formation module 1 also includes mounting seat and chip fixture (not shown).Chip fixture is pacified Loaded in mounting seat, drop micro-fluidic chip 11 is removably held on chip fixture.The setting is beneficial to micro-fluidic chip 11 fast assembling-disassembling.

In the present embodiment, mounting seat is fixed on support frame 102, and chip fixture is arranged in mounting seat.

In first embodiment, on the one hand chip fixture is used to fix drop micro-fluidic chip, by drop micro-fluidic chip 11 Be installed in mounting seat, be on the other hand additionally operable to carry out input block 13 or output block 14 it is spacing, for preventing from inputting Part 13 or output block 14 depart from the part being connected, and avoid dispersed phase fluid or continuous phase fluid or drop from leaking.

Input block 13 is connected with drop micro-fluidic chip 11, and is connected with runner system 111 with to drop micro-fluidic chip 11 convey the fluid for forming drop.Fluid for forming drop includes dispersed phase fluid and continuous phase fluid.Dispersed phase Fluid can be core liquid, covering liquid or curing agent etc..

As shown in Fig. 2 the both ends of input block 13 connect drop micro-fluidic chip 11 and will be described in detail later respectively The memory space for storing dispersed phase fluid of reagent memory module 5.

An input block 13 being connected with the core liquid memory space of reagent memory module 5 and one are shown in Fig. 2 The input block 13 being connected with the continuous phase fluid memory space of reagent memory module 5.Core liquid memory space is used to store core Core liquid.Continuous phase fluid memory space is used to store continuous phase fluid.

In the case of other, input block 13 can input other materials to drop micro-fluidic chip.

For example, when making the microballoon with layering chondritic, two input blocks can be with reagent memory module 5 Covering liquid memory space and continuous phase fluid memory space connect respectively, to input covering liquid to drop micro-fluidic chip and be used for Separate the continuous phase fluid of covering liquid, so that covering liquid is divided into covering liquid drop, then covering liquid is accordingly instilled and collects hole It is interior.Wherein, covering liquid memory space is used to store covering liquid.

For another example when being solidified by curing agent to the transition structure of core liquid drop or microballoon, two input units Part can be connected respectively with the curing agent memory space and continuous phase fluid memory space of reagent memory module 5, with micro- to drop Fluidic chip inputs curing agent and the continuous phase fluid for separating curing agent, so that curing agent is divided into curing agent drop, then Curing agent drop is accordingly instilled and collected in hole.Wherein, curing agent memory space is used to store curing agent.

In the present embodiment, first fluid entrance switchably with core liquid memory space, covering liquid memory space and solidification Agent memory space connects.

So as to which in the present embodiment, first fluid entrance with core liquid memory space when connecting, for generating core liquid liquid Drop, now, control module 4 control core liquid drop accordingly to instill in each collection hole 211.And in first fluid entrance and cladding Then it is used to generate covering liquid drop when liquid memory space connects, now, control module 4 controls covering liquid drop accordingly to instill respectively Collect in hole 211.When first fluid entrance connects with curing agent memory space, then it is used to generate curing agent drop, now, control Module 4 controls curing agent drop accordingly to instill in each collection hole 211.

The setting can allow same drop micro-fluidic chip 11 manufactured within the different periods core liquid drop, Covering liquid drop and/or curing agent drop.

Output block 14 is used to export the drop formed in coupled drop micro-fluidic chip, such as core liquid liquid Drop, covering liquid drop or curing agent drop.

Wherein, the parameter such as the length of input block 13 and output block 14, caliber can be according to the different micro-fluidic cores of drop The configuration selection of piece 11.

As shown in Fig. 2 pumping installations 12 is connected with drop micro-fluidic chip 11, and connected with runner system.Pumping installations 12 For pumping the fluid for forming drop to drop micro-fluidic chip 11.

Pumping installations 12 is fluid in the memory space for the corresponding reagent memory module 5 that control connects with pumping installations 12 The nucleus module of motion, accurately control speed and flow of flow injecting etc..Pumping installations 12 is continuous phase fluid and disperseed Phase fluid sample introduction speed and volume control device.Continuous phase fluid and the timing of the flow velocity of dispersed phase fluid one, pass through drop miniflow Control chip 11 generates drop and tended towards stability.

Control module 4 is coupled with pumping installations 12 to control pumping installations 12 to act.By the control to pumping installations 12, Dispersed phase fluid and the feed speed and flow of continuous phase fluid can be controlled, so as to control the generating rate of drop and particle diameter Deng.Specifically, the change of continuous phase fluid and the sample introduction flow rate of dispersed phase fluid control drop size can be relied on.It is scattered The flow velocity of phase fluid is bigger, and caused drop size is bigger.The flow velocity of continuous phase fluid is bigger, and it is smaller to produce drop size.Cause This, drop formation module 1, which generates drop, has the characteristics of simple to operate, repeatable.

Moreover, control module 4 can cause drop micro-fluidic chip 11 by coordinated movement of various economic factors module 3 and pumping installations 12 The drop of generation can be accordingly added dropwise in each collection hole 211 for collecting manufacture main body 21, made only independent in a collection hole A drop is accommodated, so as to avoid the reunion or cohesion between the drop needed for different microballoons.

Referring to Fig. 2, pumping installations 12 is connected by two-way input block 13 and drop micro-fluidic chip 11, and passes through connection Part connects with the corresponding memory space of reagent memory module 5.In the present embodiment, communication means are in particular to connect capillary Pipe.

Pumping installations 12 includes compression pump in first embodiment.Compression pump treats pumping fluid by compressed air and applies one Fixed pressure, drive fluid to be pumped to be pumped to the runner system 111 of drop micro-fluidic chip 11 and flowed in runner system 111. Compression pump can be pressure-actuated micro-sampling pump, due to pumping fluid by the way of no pulse, the infringement of convection body compared with It is small.

In some alternative embodiments, pumping installations can include but is not limited to：Syringe pump or aspirator.Syringe pump can be with Fluid to be pumped (as made core liquid and continuous phase fluid during core liquid drop) is promoted to be transported in drop micro-fluidic chip 11 It is dynamic.Aspirator can then vacuumize in the end of drop micro-fluidic chip 11, so as to produce negative pressure in runner system 111, pass through Pressure differential drives fluid to be pumped to be flowed in drop micro-fluidic chip 11.Pumping installations can also include accurate fluid and control Valve, piston injector etc..

Under normal circumstances, within 0.1MPa, the driving pressure of micro-fluidic chip is usually the pumping pressure of pumping installations Within 100KPa, usual 0.01~1000 μ L/min of flow velocity of the fluid in input block 13.

In first embodiment, pumping installations 12 and drop micro-fluidic chip 11 become one and are arranged at mounting seat On.

Accurate liquid separation is carried out by using pumping installations 12 and drop micro-fluidic chip 11, can be according to the predetermined ginseng of microballoon Number is estimated and realizes that liquid is added dropwise in accurate quantification in advance so that the particle diameter of prepared microballoon is more accurate.Such as have making When having the microballoon of layering chondritic, the predefined parameter as core liquid and covering liquid can be estimated in advance and accurately fixed Amount is added dropwise, make layering chondritic core and clad particle diameter it is more accurate, solution is layered spherical knot in the prior art The problem of size of core and/or the size of clad are difficult to accurately control in structure.

In the present embodiment, only runner system is illustrated with one group of folder stream focus type runner or T fonts runner, liquid therein The runner system for dripping micro-fluidic chip is the runner system of single channel drop formation.Accordingly, again illustrate only a dispersed phase stream stop into Mouth and an output port and the output port for showing a drop formation module.But in actual use, drop The runner system of micro-fluidic chip can be set including multiple runner systems, micro-fluidic chip can include multiple first fluid entrances, Multiple output ports.The setting can either simultaneously or alternately produce drop to increase efficiency, or the kind of the microballoon of increase while generation Class.

In above example, also only illustrated with drop formation module including a drop micro-fluidic chip.But liquid Drop generation module can also include multiple drop micro-fluidic chips, and each drop micro-fluidic chip can simultaneously work, can also hand over Temporary substitute is made, and can be the generation for being completely used for core liquid drop, can also have for generating the chip of core liquid drop, also may be used To have for generating the drop micro-fluidic chip of covering liquid drop, and/or can have micro- for generating the drop of curing agent drop Fluidic chip.

Furthermore it is possible to the flow area size adjustable of at least part runner of the runner system of drop micro-fluidic chip is set to save land Set.The size of size droplet diameter can be adjusted by adjusting the size of runner.Can by channel size is diminished prepare compared with The drop of small particle, can also be by the way that channel size be become greatly to prepare the drop of greater particle size.

Compared with prior art, generating drop by drop micro-fluidic chip 11 has higher precision and repeatability. The micro liquid of the μ L level volumes of 0.05pL~0.5 can be manipulated, 5~1000 μm of particle diameter drop can be formed.Such as： The liquid that corresponding volume is 25pL can form the drop that particle diameter is 40 μm.Further by physically or chemically reacting, formed Microballoon, such as form single chondritic or layering chondritic.

The composition of dispersed phase fluid and continuous phase fluid can be selected according to the needs for the microballoon to be formed.

The explanation point by taking the preparation for the layering chondritic for being used to form biological prepared Chinese ink in 3D biometric prints field as an example below Dephasing stream is stopped and the selection of continuous phase fluid.

In the layering chondritic of biological prepared Chinese ink, when making core, dispersed phase fluid is the core of layering chondritic Liquid.Wherein, core liquid can be the collagen solution comprising cell, and the number of cells contained in collagen can be 1~10⁶It is individual, example Such as 1-10⁵、1-10⁴、1-5000、1-2000、10-900、20-800、30-700、40-600、50-500、60-400、70-300、 80-200,10-100 cells.

Collagen solution is a kind of temperature sensing material, its curable at a certain temperature or liquefaction.Therefore, can be by temperature control side Formula solidifies to the core liquid drop with collagen solution.

When making clad using micro-fluidic chip 11, dispersed phase fluid is the covering liquid of layering chondritic.Cladding Liquid can be polylysine and/or sodium alginate soln.

The preparation process of polylysin solution can be：Polylysine (Sigma, Mw150,000~300,000) is dissolved in In the PH7.2 culture medium (DMEM, dulbecco's modified eagle medium) containing amino acid and glucose, obtain Concentration is 0.05% polylysin solution.Wherein, polylysin solution is a kind of temperature sensing material.Made using polylysin solution For covering liquid, it is coated in the drop of covering liquid outside core after formation clad, can be by way of temperature control by clad Curing molding.

The preparation process of sodium alginate soln can be：Sodium alginate is dissolved in DMEM culture mediums, obtaining concentration is 0.03% sodium alginate soln.

Fine droplet is generated using sodium alginate soln as covering liquid and is coated on outside core and is formed after clad, can be incited somebody to action Clad is placed in curing agent together with its internal structure, passes through chemical mode curing molding.

When generating drop using micro-fluidic chip 11, continuous phase fluid is the fluid immiscible with dispersed phase fluid.This reality Apply in example, continuous phase fluid can use the liquid immiscible with dispersed phase fluid.For example, when dispersed phase fluid is the aqueous solution, Liquid as continuous phase fluid can select fluid.

Preferably, using the gas immiscible with dispersed phase as continuous phase fluid.Using gas as continuous phase fluid When, gas will not pollute to drop.Using gas as continuous phase fluid come after shearing the drop of generation, compared to use Fluid is as continuous phase fluid, without carrying out the step, more clean and effective such as cleaning again.

It can be seen that preparing drop using drop micro-fluidic chip 11, drop formation is betided inside drop micro-fluidic chip 11. By the shear force of continuous phase fluid, the dispersed phase fluid of μ L level volumes can be dispersed into pL, nL level volume The fluid of amount, the drop of generation have less particle diameter and preferable monodispersity.For example, the volume of drop can reach 0.05pL~100nL, for generating 5-500 μm of drop, size droplet diameter is even up to 5 μm~120 μm.In addition, compared to Oscillatory type liquid separation, it is smaller on the influence of drop itself physicochemical property without dither, especially it is embodied in it and is more beneficial for keeping liquid Cytoactive inside drop.

Manufacture module 2 is collected to be used to receive the drop for being generated and being exported by drop micro-fluidic chip 11 and being formed for microballoon There is provided and prepare space and certain preparation condition.Collecting manufacture module 2 mainly includes collecting manufacture main body 21, drainage structure and rolling Movable property generating apparatus.

As shown in Figures 6 to 9, collecting manufacture main body 21 includes multiple collection holes with the action face being isolated from each other 211.Hole 211 is collected to drop to action face for collection liquid and be based on droplet formation microballoon in action face.

The drop in each collection hole 211 can be collected by each hole wall for collecting hole 211 in manufacture main body 21 is collected Journey and the forming process of microballoon are isolated, and can ensure the independence of respective process, to avoid the drop after being added dropwise mutually solidifying Poly- or reunion.The independence of the forming process of each microballoon can be ensured simultaneously, prevent mutual shadow between the transition structure of each microballoon Ring.

Control module 4 controls motion module 3, so as to control the output end for collecting manufacture main body 21 and drop formation module 1 Mouth relative motion, the process for collecting drop is realized and automatically controlled, improved drop and collect and microballoon preparation efficiency and automation Degree, and it is easy to operate.

, can be simultaneously because the action face in multiple collection holes 211 is arranged in collection manufacture main body 21 in isolation from each other The preparation of multiple microballoons is completed, so as to save preparation time, improves preparation efficiency.

In the present embodiment, collect each collection hole 211 of manufacture main body 21 or form the preparation space of microballoon.The mistake of microballoon Cross cleaning, discharge opeing of the transition structure of the formation of structure, the formation of clad, microballoon and microballoon etc. can manufacture main body collecting Carried out in 21 each collection hole 211.

Preferably, hole 211 is collected to arrange in array-like.As shown in fig. 6, these collect hole 21 manufactures main body 2 along collection Length L direction and width B direction be spaced and be evenly distributed, so set be more convenient for control module 4 control motion Module 3 completes the liquid droplet distribution to different collection holes 21.

The quantity in multiple collection holes 211 that manufacture main body 21 is provided with is collected such as can be 96,384,1536.Receive Collection manufacture main body 21 can be the orifice plate with microcavity array of standard or customization.

Collecting the size in hole 211 can determine according to the particle diameter of targeted microspheres to be prepared.In first embodiment, Mei Geshou The bottom wall 212 for collecting hole 211 is the action face in the collection hole 211.Action face is in particular super hydrophobic surface.So, After the drop that drop micro-fluidic chip 11 generates drops to the action face for collecting hole 211, drop can be in the super thin of action face Orbicule is formed in the presence of water-based.

The characteristics of device for preparing microballoon of first embodiment dexterously make use of super hydrophobic surface so that instill and collect Drop in hole 211 can be shaped to spherical or ellipsoid, form the orbicule with good sphericity, instill and collect after being easy to Covering liquid in hole 211 is coated to orbicule uniform and expectablely, and covering liquid has been carried out to orbicule Site preparation coats, and forms the layering chondritic with preferable sphericity.It can be seen that this prepares the device of microballoon, by using effect The sphericity of the super-hydrophobicity control orbicule on surface, can be realized to single chondritic or layering chondritic forming shape Control so that microballoon has more preferable sphericity.Moreover, in covering liquid in the feelings coated in action face to orbicule Under condition, action face can also play a role to the shaping of covering liquid, so as to further improve layering chondritic Sphericity.

When making the microballoon of layering chondritic, collect hole 211 and provided instead for the cross-linking reaction of core liquid and covering liquid Answer space.Specifically, first backward hole 211 of collecting instills core liquid drop and covering liquid drop to drop micro-fluidic chip 11.Core After liquid drop is instilled in the collection hole 211, core liquid drop can form orbicule in the presence of the super-hydrophobicity of action face. After covering liquid drop is instilled in the collection hole 211, be easy to covering liquid more uniformly and be fully coated on collect hole 111 in into The orbicule periphery of type.The layering chondritic that thereby may be ensured that to obtain has preferable sphericity, realizes to the layering ball The control of shape shaping structures shape.

For being used as the layering chondritic of biological prepared Chinese ink in 3D biometric prints field, the integrality of clad cladding The survival rate of the cell in core can be had a strong impact on.If outside clad coats insufficient or imperfect, cell is easy Overflowed from the breach of clad or gap, cause cell easily to be sustained damage because effective protection of clad can not be obtained, Survival rate reduces.And the embodiment is by setting the action face of super-hydrophobicity so that clad uniformly and can be wrapped fully It is overlying in core, therefore, the embodiment can effectively improve the survival rate of cell, finally improve the performance of biological prepared Chinese ink.

The effect after super-hydrophobic processing is carried out to action face in order to be shown more clearly that, compares and shows in Fig. 7 and Fig. 8 Drop instill it is unprocessed and after treatment collect hole 211 bottom wall 212 when forming shape.

As shown in Figure 7 and Figure 8, for the bottom wall in the first collection hole 211 in left side without super-hydrophobic processing, liquid, which instills, collects hole After in 211, droplet profile is in platypelloid type；The bottom wall 212 to several collection holes 211 on right side is played by super thin in second, left side Water process, after liquid is instilled in collection hole 211, droplet profile is spherical in shape.

The super-hydrophobicity of action face can be by carrying out super-hydrophobic place to the bottom wall 212 for collecting hole 211 in the embodiment Reason obtains；Super-hydrophobic material can also be utilized to make and collect manufacture main body 21.

Wherein, by collect hole 211 bottom wall 212 carry out it is super-hydrophobic handle obtain super-hydrophobicity action face it is excellent The mode is selected to be：Manufacture main body 21 acetone, absolute ethyl alcohol, deionized water etc. will be collected in clean room to embathe or clean dedusting, Then super hydrophobic coating is applied to the inner surface for collecting hole 211 with modes such as immersion or spray gun sprayings, be placed in insulating box afterwards It is interior to heat and dry.Super hydrophobic coating meets such as can be the coating or nano-sized hydrophobic layer for handling to obtain through various perfluorinates The material of biocompatibility.

The bottom wall for collecting hole is preferably lower concave curved surface.

Acted on using the center convergence of lower concave curved surface, microballoon can be caused to be more easy to be shaped to orbicule.For example, preparing When being layered chondritic, lower concave curved surface can make core liquid drop be easier to be shaped to orbicule, so that core has more Good sphericity, and can cause covering liquid more rapidly and fully be coated on orbicule, further improve covered effect, Improve coating efficiency.

It can be seen that the device for preparing microballoon of the present embodiment can not only utilize the hydrophobicity feature control microballoon of action face Forming shape and sphericity, but also the convergence guide effect of lower concave curved surface can be utilized further to improve the spherical knot of layering The sphericity of structure, and further improve the coating efficiency of core liquid and/or covering liquid to orbicule.

As shown in fig. 7, in first embodiment, collecting manufacture main body 21 includes multiple collection holes 21, each bottom for collecting hole 21 Wall 212 is domed lower concave curved surface.Domed lower concave curved surface is beneficial to form spherical orbicule.

In other unshowned embodiments, lower concave curved surface can also be the lower concave curved surface of U-shape structure.U-shape structure Lower concave curved surface be beneficial to formed elliposoidal it is spherical stop.

As shown in figure 8, in an alternative embodiment, the bottom wall 212 for collecting the collection hole 211 of manufacture main body 21 can also For plane.

During prepared by microballoon, collect in hole 211 and there may be residual liquid, such as unnecessary covering liquid, cleaning fluid Or curing agent etc..In order that residual liquid can discharge in time, collecting manufacture module 2 also includes drainage structure.Drainage structure For discharging the residual liquid collected in microballoon preparation process in hole 211.

In the present embodiment, drainage structure includes outage 213 and the closeouts being arranged on the bottom wall 212 for collecting hole 211. Closeouts are used to block outage 213.Wherein, closeouts and outage 213 are detachably connected.

Outage 213 is blocked before discharge opeing, opens outage 213 again when needing discharge opeing.So, when microballoon preparation process In when needing to discharge residual liquid, only need to pull down closeouts from outage 213 makes residual liquid from outage 213 Outflow, and after residual liquid excludes clean again will closeouts closure it is spherical with outage, can ensure to be layered again Structure preparation process is smoothed out, and conveniently and is easily achieved.

In an alternative embodiment, drainage structure includes the outage being arranged in the side wall for collecting hole 211.Now, Drainage structure preferably also includes tilting gearing, and tilting gearing is used to control when the residual liquid in hole is collected in discharge collects hole Tilted towards the side wall side provided with outage.The setting of tilting gearing can either ensure the discharge of residual liquid, can keep away again Exempt to influence the preparation of microballoon because setting drainage structure, it is particularly possible to avoid drainage structure from influenceing core liquid in action face Molding effect influences covered effect of the covering liquid in action face.

Preferably, control module coupled with tilting gearing with control tilting gearing action with realize tilting gearing it is automatic, Accurate control.

Moreover, in order to prevent that will collect the orbicule in hole 211 by mistake during residual liquid is discharged discharges, and can incite somebody to action The pore size of outage is set smaller than the particle diameter for the orbicule that core liquid is formed.The aperture of outage is less than core liquid institute The particle diameter of the orbicule of formation, then it is necessarily less than particle diameter of microballoon, therefore, it is possible to avoid orbicule and microballoon from misprinting out.

In addition, closeouts it is not necessary to, in the case where being not provided with closeouts, the residual liquid higher than outage can To discharge at any time.

The example that outage 213 is set on the bottom wall 212 in the collection hole 211 of orifice plate 21 is shown in Fig. 9.In order to prevent Instill the drop collected in hole 211 not discharge from outage 213 before discharge opeing, collect hole 211 before discharge opeing in closure shape State.

It is the spherical knot of layering when preparing single chondritic and being layered the core of chondritic, and in the microballoon of preparation During structure, in order that core liquid drop more rapid and better forms orbicule, and hole is collected to make covering liquid more uniformly be coated on In 211 on formed orbicule, hole can be rocked during core liquid drop forming and covering liquid are coated on orbicule Plate, rock that more rapid and better balling-up, covering liquid are uniformly wrapped on the orbicule collected in hole to make core liquid drop by this On.

Therefore, in the present embodiment, collecting manufacture module 2 also includes rocking generation device, rocks generation device and is used in shape Into rocking for the material balling-up for producing during microballoon collection manufacture main body 21 to make to form microballoon.

Preferably, control module 4 couples with rocking generation device and rocks generation device action to control to realize rolling movable property Automatic, the accurate control of generating apparatus.

Because the action face in each collection hole 211 is isolated from each other, therefore, even if rocking collection manufacture main body 21, also not Each collection hole 211 can be caused to interfere, so as to generation device rocked by this come realize it is required rock, enter one Step improves the molding effect that microballoon is especially layered chondritic.

The lower section or side for collecting manufacture main body 2 can be arranged at by rocking generation device.

In the present embodiment, collect manufacture main body 21 and be removably disposed.

Collect manufacture main body 21 to be removably disposed, the demand that can be prepared according to microballoon, which is changed, suitably collects manufacture master Body 21.In addition, it is also beneficial to improve the preparation efficiency of microballoon in some cases.For example, generated in drop micro-fluidic chip 11 During instillation drop, a certain manufacture main body 21 of collecting is set to be located at the lower section of drop micro-fluidic chip 11 to receive the liquid of generation Drop, and after drop formation and collection process terminate, the collection can be manufactured to main body 21 and separate and be placed on the second temperature control mould Temperature control curing process is carried out on the temperature control console of block 6, to cause the drop in collection manufacture main body 21 to solidify.At the same time, Another piece can be collected and manufacture main body 21 and be placed in the lower section of drop micro-fluidic chip 11, to maintain drop formation and instillation process Continuation, so as to improve preparation efficiency.

Motion module 3 is used to be connected with the output port of drop formation module 1 and/or collection manufacture main body 21, with driving The output port of drop formation module 1 and/or the collection manufacture relative motion of main body 21 collect hole so that each drop accordingly drops to In 211 action face.

Control module 4 is coupled with motion module 3 to control motion module 3 to move, so as to automatically and accurately control drop Instill position.

In first embodiment, motion module 3 includes chip motion device and bulk motion device.

Bulk motion device is used to control collection manufacture main body 21 to move.Control module 4 coupled with bulk motion device with Control bulk motion device action.Specifically, bulk motion device includes being used to control collection manufacture main body to transport in the horizontal plane Dynamic main body horizontal movement component.

Main body horizontal movement component includes motion platform, collects manufacture main body 21 and is removably attachable on motion platform. Motion platform can drive collection manufacture main body 21 to be moved horizontally on base station 101.

Specifically, slot is set on motion platform, collect manufacture main body 21 can insert in the horizontal direction in slot or from Extracted out in the slot, the detachably connected of manufacture main body 21 and motion platform is collected so as to realize.

Chip motion device is used to control drop micro-fluidic chip 11 to move.Wherein, the output port of drop formation module 1 It is synchronized with the movement with drop micro-fluidic chip 11.Control module 4 couples with chip motion device to be acted with control chip telecontrol equipment.

Specifically, the chip that chip motion device includes being used to control drop micro-fluidic chip 11 to move along the vertical direction hangs down Straight moving parts.As shown in figure 1, in first embodiment, Chip Vertical moving parts are mounted in the bottom of drop formation module 1 Portion, for driving drop micro-fluidic chip 11 and the output port of drop formation module 1 vertically to move up and down.

Set Chip Vertical moving parts to be advantageous to adjust the height of output port on demand, especially treat instillation material viscosity When higher, it can be realized by Chip Vertical moving parts and collect instillation in hole 211, be difficult to hang beneficial to solving heavy viscous material The problem of drop.

It can be seen that control module 4 to the control of Chip Vertical moving parts by controlling the upper of drop micro-fluidic chip 11 Lower motion, collection manufacture main body 21 is controlled to move in the horizontal plane by the control to main body horizontal movement component.Therefore, may be used Row regulates and controls when with the output port to drop formation module 1 within the specific limits and collecting the relative position for manufacturing main body 21, from And the drop for controlling drop micro-fluidic chip 11 to generate instills corresponding collect in hole 211 one by one.

In the present embodiment, it is accurately aligned with positioning to realize the output port of drop formation module 1 with collecting hole 211, it is main The kinematic accuracy of body horizontal movement component can be 0.01mm.The kinematic accuracy can meet in 3D biometric prints field as life The preparation requirement of the microballoon of thing prepared Chinese ink, is unlikely to excessive increase design and processing cost again.

Reagent memory module 5 includes core liquid memory space, covering liquid memory space, curing agent memory space, cleaning fluid Memory space and continuous phase fluid memory space.The quantity of various memory spaces can increase and decrease on demand.

In the present embodiment, each memory space uses piston seal, core liquid memory space, covering liquid memory space, solidification The piston of agent memory space and continuous phase fluid memory space comprises at least two interfaces, is connected pump by communication means all the way The air inlet of device 12, the sample introduction of drop micro-fluidic chip 11 is connected by input block all the way.

Some materials of microballoon of the preparation with bioactivity as used in during layering chondritic have certain to temperature It is required that the core liquid containing cell requires that temperature can ensure the activity of its internal cell inside such as.It is this kind of micro- in order to meet Requirement of the ball to temperature is, it is necessary to which the temperature that material is prepared to core liquid, covering liquid etc. is controlled.Therefore, prepare the dress of microballoon Put and be additionally provided with the first temperature control module.First temperature control module control core liquid, covering liquid, curing agent, cleaning fluid and continuous phase stream The temperature of at least one of body.

First temperature control module is arranged at reagent memory module 5, the temperature of the material for controlling each memory space memory storage Degree.

First temperature control module includes multiple material structure of controlling temperature independent of each other, and each memory space is correspondingly arranged on material Expect structure of controlling temperature, each material structure of controlling temperature is controlled to the temperature of the material of corresponding storage space memory storage.Each material temperature The control temperature of control structure can be independently arranged, therefore, the different storage temperatures that can be needed according to material in memory space To set control temperature, the temperature of each memory space, which is accomplished, not to be interfere with each other.

In the present embodiment, each separate material structure of controlling temperature of the first temperature control module is arranged at the bottom of corresponding memory space Between base station 101.Multiple material structure of controlling temperature include the core liquid structure of controlling temperature of the temperature for controlling core liquid, for controlling The covering liquid structure of controlling temperature of the temperature of covering liquid processed, the curing agent structure of controlling temperature of the temperature for controlling curing agent, for controlling The continuous phase fluid structure of controlling temperature of the cleaning fluid structure of controlling temperature of the temperature of cleaning fluid and the temperature for controlling continuous phase fluid.

Core liquid structure of controlling temperature corresponding with core liquid memory space can ensure cell in core liquid in preparation process It is middle to keep good activity, it is used as biological ink to be finally prepared in the drop with bioactivity or 3D biometric prints field The microballoon of juice.Covering liquid structure of controlling temperature corresponding with covering liquid memory space will not be to core when can ensure to be coated on orbicule The environment temperature of cell in liquid causes big fluctuation, so as to keep good work during active microballoon is prepared Property.Continuous phase fluid structure of controlling temperature corresponding with continuous phase fluid memory space can ensure continuous phase fluid in core liquid The environment temperature of cell will not cause big fluctuation, be kept well during active layering chondritic is prepared Activity.Curing agent structure of controlling temperature and cleaning fluid structure of controlling temperature are respectively used to control the temperature of curing agent and cleaning fluid to use to reduce Adversely affected when curing agent or use cleaning fluid to caused by the physicochemical property of core or clad.

The temperature of material in hole 211 is collected in the control of second temperature control module 6.Second temperature control module 6 can be to collecting in hole 211 Orbicule carry out temperature control solidification.Orbicule to be solidified can be core liquid drop, the microballoon with uncured clad Transition structure.

Second temperature control module has the situation of temperature sensing material suitable for the structure to be solidified of orbicule to be solidified.

Control module 4 includes the solidification temperature control unit coupled with the second temperature control module 6, can be set according to different materials The control temperature of solidification temperature control unit, to meet the solidification demand of different orbicules to be solidified.

As shown in figure 1, in the present embodiment, by the way that the temperature control console for manufacturing main body 21 and moving to the second temperature control module 6 will be collected On carry out temperature control solidification to collecting the orbicule to be solidified in manufacture main body 21.

Orbicule to be solidified is solidified by the way of temperature control solidification, on the one hand makes the temperature in collection hole 211 The physicochemical property of the material in collection hole 211, the activity of cell especially in core liquid drop, on the other hand when need can be ensured When solidifying to core and/or clad, it can also be controlled by second temperature control module 6 and collect orbicule in hole 211 Temperature reach the solidification temperature of core liquid and/or covering liquid, realize that temperature control solidifies.

In this embodiment, the second temperature control module 6 includes semiconductor chilling plate, heat abstractor and temperature control console.

Wherein, semiconductor chilling plate is arranged on below temperature control console and is electrically connected with the solidification temperature control unit of control module 4 Connect so that temperature control console to be heated or cooled under the control of solidification temperature control unit.Temperature control is placed in when collecting manufacture main body 2 When on platform, you can the temperature for collecting the material in the collection hole 211 for manufacturing main body 2 is controlled.

Heat abstractor is used to realize the heat transfer between semiconductor chilling plate and environment, and it is arranged on semiconductor chilling plate Bottom.Semiconductor chilling plate has temperature control end and non-temperature control end, and temperature control end is set towards temperature control console, non-temperature control end direction radiating Device is set.

In order to ensure that heat transfer is uniform, in this embodiment, temperature control console includes soaking plate.The soaking plate, which can be realized, partly to be led Uniform heat transmission between body cooling piece and the collection manufacture main body 21 being placed on temperature control console.

Second temperature control module 6 is set so that each Rotating fields of microballoon need not be carried out using curing agent when preparing microballoon Solidification.For example, when manufacture is layered chondritic, collagen solution can be used to prepare core as core liquid, using poly- bad ammonia Acid solution prepares clad as covering liquid.By way of temperature control solidification, curing agent curing mode can be avoided to live cell Property infringement, prepared core or be layered chondritic particle diameter it is also more accurate.

In other unshowned embodiments, the second temperature control module directly can also be arranged at collection manufacture main body and fortune Between moving platform, such setting can make orbicule in-situ solidifying in collection hole, assemble in situ and form the spherical knot of layering Structure.

In the present embodiment, the concrete structure of each independent material structure of controlling temperature of the first temperature control module may be referred to the second temperature Control the concrete structure of module.

In addition, in this embodiment, preparing the device of microballoon also includes pretreatment module (not shown).

Wherein, the pretreatment module is connected to reagent memory module 5, be specifically connected to core liquid memory space and Covering liquid memory space, for making electric charge opposite with collecting orbicule molded in hole 211 on core liquid or covering liquid band, Collected in order to which core liquid or covering liquid are coated on orbicule molded in hole.

In first embodiment, control module 4 includes the motion module control unit and pumping installations coupled with motion module 3 The pumping installations control units of 12 couplings, the solidification temperature control unit coupled with the second temperature control module 6, couple with the first temperature control module Material temperature control unit, with rock that generation device couples rock generation device control unit etc..

In the present embodiment, control module 4 has gathered various control functions, and realization prepares each part of the device of microballoon Co-ordination, possess following functions：

Instruction is sent to motion module 3, and what manufacture main body 21 was collected in adjustment collects the defeated of hole 211 and drop formation module 1 Relative position between exit port, to cause the drop that drop micro-fluidic chip 11 generates to be instilled into one by one in collection hole 211, one A drop is only individually accommodated in individual collection hole 211.

To pumping installations 12 send instruct, adjust pumping installations 12 sample rate and sample size, with cause drop formation, It is relative between hole 211 and the output port of drop formation module 1 that collecting for manufacture main body 21 is collected in the speed of instillation and adjustment Position mutually cooperates with, and controls the particle diameter of drop.

Generation device action is rocked in control when needing, to accelerate the forming efficiency of microballoon, ensure that clad is evenly coated.

Pass through the temperature at least part material for controlling the control reagent memory module storage of the first temperature control module, especially core The temperature of core liquid and covering liquid.

Control is placed in the solidification temperature for collecting the orbicule in hole of the collection manufacture main body of the second temperature control module.

Second embodiment

Second embodiment gives another specific embodiment of the device for preparing microballoon of the present invention.Figure 10 and Figure 11 show The structural representation of the device for preparing microballoon of second embodiment of the invention is gone out.

As shown in Figure 10, the device for preparing microballoon of second embodiment of the invention includes drop formation module, collects manufacture Module, motion module 3, control module 4, reagent memory module 5, the first temperature control module, the second temperature control module 6, liquid relief module 7, Replace pipette tips module 8, waste material box 9, pretreatment module and pedestal 10.

Drop formation module includes drop micro-fluidic chip 11 and pumping installations 12, input block 13 and output block 14.

Pedestal 10 includes base station 101 and the support frame 102 being connected with base station 101.

The logical control chip 11 of drop miniflow, collect manufacture module, motion module 3, reagent memory module 5, the second temperature control module 6th, pipette tips module 8 is replaced, waste material box 9 may be contained within base station 101.Liquid relief module 7 is arranged on support frame 102.

Control module 4 and pumping installations 12 are separately provided.Certainly, in an optional embodiment, the He of control module 4 Pumping installations 12 can also be arranged on pedestal 10.

Wherein, drop micro-fluidic chip 11 is fixedly installed on the base station 101 of pedestal 10.The output section of drop formation module Part 13 is connected to export drop with the runner system of drop micro-fluidic chip 11.In the present embodiment, the outlet of output block 13 is fixed Set.

In second embodiment, motion module 3 includes being used to control collecting the main body that manufacture main body 21 is moved in the horizontal plane Horizontal movement component.Control module 4 couples with main body horizontal movement component, to control main body horizontal movement component to act, and then Control drop is accordingly instilled in each collection hole 211 for collecting manufacture main body 21.

In second embodiment, collecting manufacture module 2 also includes drainage structure, and drainage structure is received after forming microballoon for discharge Collect the residual liquid in hole.

As shown in figure 11, the drainage structure of the collection manufacture module 2 of second embodiment includes the discharge opeing main body for discharge opeing 23 and vacuum suction apparatus 22.

In the present embodiment, in order to avoid when preparing the drops such as core liquid drop, drop is misprinted in the case of uncured Go out, be to be not provided with the orifice plate of outage for receiving the collection manufacture main body 21 of drop.Solidify in core liquid drop or clad After completing to form the orbicule of solidification, the orbicule of solidification is moved into discharge opeing main body 23 and carries out discharge opeing operation again.

Discharge opeing main body 23 includes multiple collection holes 231, and outage 233 is provided with the bottom wall 232 for collecting hole 231.Row Liquid main body 23 is in particular discharge opeing orifice plate

Vacuum suction apparatus 22 is used for by the residual liquid in the collected at suction hole 231 of outage 233.

Vacuum suction apparatus 22 includes suction chamber 221 and vacuum generator 222.Suction chamber 221 is arranged at discharge opeing main body 23 Collection hole 231 lower section and connected with outage 233.Vacuum generator 222 is connected with suction chamber 221 so that suction chamber 221 Interior formation vacuum.Control module 4 is coupled with vacuum generator 222 to control vacuum generator 222 to act.

It is sucked by vacuum and 22 set-up modes for combining discharge opeing main bodys 23 is set, unnecessary covering liquid etc. is residual during ease of assembly Extraction raffinate body filters out operation, and beneficial to the residual liquid emptying in outage 231.

The big I of outage 233 wherein in discharge opeing main body 23 is according to the particle diameter or core for preparing different size of microballoon Particle diameter determine that the diameter of the outage 231 should be less than the collection hole 231 during discharge opeing, the external diameter of interior orbicule.

Liquid relief module is used for into instillation covering liquid, curing agent and cleaning fluid in the collection hole 211 for collecting manufacture main body 21 At least one.

When preparing the device of microballoon and being provided with liquid relief module, core liquid is completed when preparing and instiling by drop formation module 11 , can be by liquid relief module quickly and conveniently instillation covering liquid drop after drop, can meet multilayer orbicule structure prepares need Will, and take into account preparation efficiency.Certainly, core liquid drop can be entered between core liquid drop instils and covering liquid drop instils Row curing process.

Control module 4 is coupled with liquid relief module to control liquid relief module action.

Specifically, liquid relief module includes liquid-transfering gun 7, and preparing the device of microballoon also includes replacing pipette tips storage module 8, replaces Pipette tips storage module 8 is used for the replacement pipette tips for storing liquid-transfering gun 7.

In addition, as shown in Figure 10, preparing the device of microballoon also includes waste material box 9.Waste material box 9 is used to receive and store useless Material.

The liquid separation that liquid-transfering gun 7 is used for tens micro updating above liquid operates, and replacement pipette tips storage module 8, waste material box 9 are One uses.In the present embodiment, liquid-transfering gun 7 can be the liquid relief product of standard.

In second embodiment, control module 4 includes the motion module control unit and pumping installations coupled with motion module 3 The pumping installations control units of 12 couplings, the solidification temperature control unit coupled with the second temperature control module 6, couple with the first temperature control module Material temperature control unit, coupled with liquid relief module liquid relief module control unit, with the vacuum control that couples of vacuum suction module Portion etc..

In the present embodiment, control module 4 possesses following functions：

Send and instruct to pumping installations 12, the sample rate and sample size of pumping installations 12 are adjusted, to cause drop formation It is relative between hole 211 and the output port of drop formation module 1 that collecting for manufacture main body 21 is collected in the speed of instillation and adjustment Position mutually cooperates with, and also controls the particle diameter of the drop of drop formation module generation.

The temperature of at least part material of reagent memory module storage is controlled by controlling the first temperature control module, especially The temperature of core liquid and covering liquid.

The vacuum of suction chamber 221 is adjusted, the residual liquid in hole 231 is collected with discharge；

Send and instruct to liquid-transfering gun 71, adjust keying, position and the drop formation speed of liquid-transfering gun 71, and control moves Liquid rifle 71 changes pipette tips etc..

Unaccounted part refers to the related content of first embodiment in second embodiment.

3rd embodiment

3rd embodiment provides a specific embodiment of the method for preparing microballoon of the present invention.The preparation of 3rd embodiment The device for preparing microballoon that the method for microballoon can cross first embodiment of the invention is implemented.

The method that explanation prepares microballoon exemplified by manufacturing not stratified single chondritic in 3rd embodiment.

Single chondritic manufactured in the present embodiment is the solid-state microballon of single of unassembled clad.The body of solid-state microballon Product is 0.05pL-100nL.The solid-state microballon is specially calcium-alginate bead.

Illustrate the specific method for preparing microballoon of the calcium-alginate bead below.

The method for preparing microballoon includes core liquid drop formation and collection step and microballoon generation step.

Core liquid drop formation and collection step include：Core liquid is passed through into drop micro-fluidic chip with micro- by drop Fluidic chip generates core liquid drop；Core liquid drop is dropped to correspondingly and collects the different collection holes for manufacturing main body In action face.Also include：Continuous phase fluid is passed through into drop micro-fluidic chip so that continuous phase fluid is in micro-fluidic chip Runner system in separate core liquid generation core liquid drop, continuous phase fluid and core liquid are immiscible.Continuous phase fluid is gas.

In the present embodiment, core liquid drop formation and collection step specifically include step a, by pumping installations 12 by reagent The gas as continuous phase fluid in memory module 5 is pumped into the second flow channel 111B of drop micro-fluidic chip 11；Step B, by pumping installations 12, the first flow of drop micro-fluidic chip 11 will be injected as the sodium alginate soln of dispersed phase fluid In 111A, for dispersed phase fluid under the shearing force of continuous phase fluid, the particle diameter for forming single dispersing arrangement is 10 μm -500 μm Core liquid drop；Step c, the core liquid drop formed in step b is collected to the collection hole 211 for collecting manufacture main body 21 It is interior, the main body horizontal movement component and liquid for collecting manufacture main body 21 bottom are arranged on during collection by the control of control module 4 The speed motion that drop generating rate matches, realize that the one-to-one storage to collecting hole 211 of drop is collected successively；Step D, repeat step a are to step c, until collecting each collect in hole in manufacture main body accommodates a core liquid drop.

Microballoon generation step, it is included in the action face for collecting hole and is based on core liquid droplet formation microballoon.Including Curing schedule, curing schedule include carrying out curing process to the orbicule by core liquid droplet formation collected in hole.

In 3rd embodiment, microballoon generation step specifically includes：Step e, using calcium chloride solution as curing agent, make simultaneously Sodium alginate soln is substituted for dispersed phase fluid to repeat the above steps a~step d, until collecting in each collection hole of manufacture main body Instiling has curing agent drop, and solidifies core liquid droplet formation calcium alginate in each collection hole for collecting manufacture main body Microballon；Step f, extraction raffinate remove step, and the remaining curing agent collected in hole is removed by outage.

Fourth embodiment

Fourth embodiment provides a specific embodiment of the method for preparing microballoon of the present invention.The system of fourth embodiment The device for preparing microballoon that the method for standby microballoon can cross first embodiment of the invention is implemented.It is layered in fourth embodiment with manufacturing Illustrate the preparation of microballoon exemplified by chondritic.The layering chondritic is used specifically as the biological prepared Chinese ink of 3D printing.

The method for preparing microballoon of the layering chondritic of fourth embodiment includes core liquid drop formation and collection step With microballoon generation step.

Core liquid drop formation and collection step can be found in the related content of 3rd embodiment.

Microballoon generation step, which is included in collect in hole, is based on core liquid droplet formation microballoon.Including curing schedule and bag Coating generation step.Curing schedule includes the temperature of the orbicule in control collection hole with the carry out curing process to orbicule. Clad generation step includes：Covering liquid drop formation and collection step, including covering liquid is generated by drop micro-fluidic chip Drop, and covering liquid drop is dropped in the action face in different collection holes correspondingly；Encapsulation steps, including make to drop to Covering liquid drop in action face is coated on the outside of the orbicule collected in hole to form clad.

Microballoon generation step specifically includes in fourth embodiment：Step e, it will collect and manufacture main body the second temperature control module of dislocation Carry out temperature control and be formed by curing core, solidification temperature is 37 ° or so, and hardening time is or so half an hour；Step f, it will collect and manufacture Main body 21 is moved back on the motion platform of main body horizontal movement component, utilizes the instillation covering liquid of drop micro-fluidic chip 11, covering liquid For polylysin solution, specifically, sodium alginate is substituted using polylysin solution as covering liquid, while as dispersed phase fluid Solution repeats the above steps a~step d, has covering liquid drop until collecting and being instiled in each collection hole of manufacture main body；Step G, stand a period of time wait covering liquid drop and form clad in core periphery；Step h, extraction raffinate remove step, remove and collect Remaining covering liquid in hole, remaining covering liquid is removed in particular by outage in the present embodiment；Step i, cladding is changed on demand The material of liquid, and the covering liquid of repeat step f-h, the instillation second layer or more layers.

5th embodiment

5th embodiment provides a specific embodiment of the method for preparing microballoon of the present invention.The system of 5th embodiment The device for preparing microballoon that the method for standby microballoon can cross second embodiment of the invention is implemented.It is layered in 5th embodiment with preparing The method that explanation prepares microballoon exemplified by chondritic.The layering chondritic is used specifically as the biological prepared Chinese ink of 3D printing.

The method for preparing microballoon of the layering chondritic of 5th embodiment includes core liquid drop formation and collection step With microballoon generation step.

Core liquid drop formation and collection step referring to 3rd embodiment related content.

Microballoon generation step, which is included in collect in hole, is based on core liquid droplet formation microballoon.Including curing schedule and bag Coating generation step.Curing schedule includes the temperature of the orbicule in control collection hole with the carry out curing process to orbicule. Clad generation step includes：Covering liquid drop formation and collection step, including covering liquid drop is generated by liquid relief module, and Covering liquid drop is dropped to correspondingly in the action face in different collection holes；Encapsulation steps, including make to drop to effect table Covering liquid drop on face is coated on the outside of the orbicule collected in hole to form clad.

Microballoon generation step specifically includes in 5th embodiment：Step e, it will collect and manufacture main body the second temperature control module of dislocation Carry out temperature control and be formed by curing core, solidification temperature is 37 ° or so, and hardening time is or so half an hour；Step f, it will collect and manufacture Main body 21 is moved back on the motion platform of main body horizontal movement component, using liquid relief module, installs the bag for including first layer clad additional The pipette tips of covering liquid, the polylysin solution to instil as covering liquid, have until collecting and being instiled in each collection hole of manufacture main body Covering liquid drop；Step g, stand a period of time wait covering liquid drop and form clad in core periphery；Step h, extraction raffinate are clear Except step, the remaining covering liquid collected in hole is removed, specifically first moves to the interior each structure and material for collecting manufacture main body Discharge opeing main body, then remaining covering liquid is removed from the outage of discharge opeing main body by way of vacuumizing, then by discharge opeing main body Material is moved back to collection manufacture main body；Step i, the pipette tips of the covering liquid with next layer of clad, and repeat step are changed on demand F-h, form the covering liquid of the second layer or more layer.

In the present embodiment, it can use and be the reason for liquid relief module instillation covering liquid：In order to ensure the abundant of covering liquid Cladding, it usually needs instil excessive covering liquid, therefore the volume that covering liquid instils is larger, liquid-transfering gun (or other existing shiftings Liquid device) such required precision can be met.In the present embodiment, it can meet to wrap come the covering liquid drop that instils using liquid-transfering gun The Grained Requirements that covering liquid drop instils, while also possess higher instillation efficiency.

As long as it should be noted that in place of noncontradictory, present invention any embodiment described above, any embodiment are replaced It can be applied in combination for the technological means used in embodiment or optional embodiment.For example, in the dress on preparing microballoon In each embodiment put, the vacuum suction apparatus in the drainage structure of second embodiment can manufacture with the collection of first embodiment Body combination；Similarly, the closeouts that are referred in first embodiment or its alternate embodiment, it is arranged in the side wall for collecting hole The structures such as outage, tilting gearing can also be with the discharge opeing body combination of second embodiment.

In addition, for realize that the unwanted each structure of general object of the present invention and step in the specific implementation can roots According to needing to omit；Of course for more excellent technique effect, other technologies can also be increased on the basis of various embodiments of the present invention Means.

From the above description, it can be seen that above example of the present invention can at least realize one of following technique effect：

1st, the process of drop formation is put into inside drop micro-fluidic chip, by the shear force of two-phase fluid, energy It is enough that μ L levels liquid dispersions can be reached 0.05pL-100nL, be used for into the fluid with pL, nL level volume, the volume of drop 5-500 μm of drop is generated, especially generates 5-120 μm of drop.The drop of generation has less particle diameter and preferably single point Dissipate property.This mode is without dither, compared to the mode of oscillatory type liquid separation, drop self-characteristic is influenceed it is smaller, especially It is embodied in its cytoactive for being more beneficial for keeping drop internal.

2nd, the structure design by drop micro-fluidic chip in itself, monodispersed liquid is generated inside drop micro-fluidic chip Drop, and by the design of runner system, instead of it is traditional utilize small long capillary to carry out drop arrangement, reduce space hold. And it can be arranged with monodisperse and single and pass sequentially through and export drop, on the one hand be easy to physics dynamic during drop formation, the opposing party Face can generate form of drop etc. by observation by light microscope again.Drop is produced by drop micro-fluidic chip, is simplified The control condition of drop formation process, improve preparation efficiency.The speed of generation drop can reach tens of thousands of per second.Do not easily cause Cross pollution, particle diameter is smaller, is easily manipulated, and production efficiency is higher.

3rd, integrated drop micro-fluidic chip, pumping installations, reagent memory module, collection manufacture module, motion module are passed through And control module, pumping installations drive the different fluid in reagent memory module to enter drop micro-fluidic chip, drop is micro-fluidic Chip after being spontaneously generated drop inside it, is exported to removable according to continuous phase fluid and the fluid rate of dispersed phase fluid ratio Dynamic collection manufacture main body, output and storage that the drop of generation quantitatively positions are realized, it is convenient to carry out incubated, vibration mixing Deng microballoon preparation manipulation.

4th, the motion module that is prepared by control module to microballoon, pumping installations, rock generation device etc. and controlled automatically System, automaticity is high, it is high to collect preparation efficiency, easy to operate.

5th, control module 4 controls the drop of drop micro-fluidic chip generation to instill in each collection hole collected in manufacture main body Make one to collect and a drop is only individually accommodated in hole, the reunion or solidifying between the drop needed for different microballoons can be avoided It is poly-.

The exemplary embodiment of the present invention is these are only, is not intended to limit the invention, it is all in the spiritual and former of the present invention Within then, any modification, equivalent substitution and improvements made etc., it should be included in the scope of the protection.

Claims

A kind of 1. device for preparing microballoon, it is characterised in that including：

Drop formation module, the drop formation module include first fluid entrance, drop micro-fluidic chip and output port, institute Stating drop micro-fluidic chip includes runner system, and the first fluid entrance and the output port connect with the runner system respectively Logical, the drop micro-fluidic chip is used to form the dispersed phase fluid entered in the runner system from the first fluid entrance Drop simultaneously exports the drop from the output port；

Manufacture module is collected, the manufacture module of collecting includes collecting manufacture main body, and the manufacture main body of collecting includes each tool There are multiple collection holes of action face, each action face for collecting hole is isolated from each other, and the collection hole is described for receiving Drop is based on the droplet formation microballoon to the action face and in the action face；

Motion module, the motion module manufactures main body drive connection with the output port and/or described collect, in institute State and produce relative motion so that each drop accordingly drops to the collection between output port and the collection manufacture main body In the action face in hole；

Control module, the control module are coupled with the drop formation module to control described in the drop formation module generation Drop, and the control module is coupled with the motion module to control the motion module to act.
2. the device according to claim 1 for preparing microballoon, it is characterised in that the drop formation module also includes being used for The second fluid entrance of continuous phase fluid is passed through, the continuous phase fluid is used for the dispersed phase fluid in the runner system It is divided into the drop, wherein,

The runner system includes folder stream focus type runner, and the folder stream focus type runner includes first flow and is arranged at described the One runner both sides and two second flow channels connected with the first flow, the first flow connect with the first fluid entrance Pass to and be passed through the dispersed phase fluid, the second flow channel is connected with the second fluid entrance to be passed through the continuous phase stream Body；And/or

The runner system includes T-shaped runner, and the T-shaped runner includes third flow channel and intersects at described the with the third flow channel The 4th runner in the middle part of three runners, the third flow channel are connected to be passed through the continuous phase fluid with the second fluid entrance, 4th runner is connected with the first fluid entrance to be passed through the dispersed phase fluid.
3. the device according to claim 1 for preparing microballoon, it is characterised in that the runner system of the drop micro-fluidic chip Inner surface be hydrophobic surface, it is therefore preferable to super hydrophobic surface.
4. the device according to claim 1 for preparing microballoon, it is characterised in that the drop micro-fluidic chip is removably Set.
5. the device according to claim 4 for preparing microballoon, it is characterised in that the drop formation module also includes installation Base and chip fixture, the chip fixture are installed in the mounting seat, and the drop micro-fluidic chip removably presss from both sides It is held on the chip fixture.
6. the device according to claim 1 for preparing microballoon, it is characterised in that the drop formation module also includes input Part, the input block connect with the runner system, to convey the fluid for forming the drop to the runner system.
7. the device according to claim 1 for preparing microballoon, it is characterised in that the drop formation module also includes pumping Device, the pumping installations connect with the runner system, to pump the fluid for forming the drop to the runner system.
8. the device according to claim 7 for preparing microballoon, it is characterised in that the pumping installations and the drop miniflow Control integrated chip is integrated；Or the pumping installations and the drop micro-fluidic chip split settings.
9. the device according to claim 7 for preparing microballoon, it is characterised in that the control module and the pumping installations Couple to control the pumping installations to act.
10. the device according to claim 1 for preparing microballoon, it is characterised in that

The drop micro-fluidic chip includes runner system described in two or more；And/or

The drop formation module includes first fluid entrance described in two or more；And/or

The drop formation module includes output port described in two or more；And/or

The drop formation module includes multiple micro-fluidic chips.
11. the device according to claim 1 for preparing microballoon, it is characterised in that the inner surface of the output port is thin Aqueous surface, it is therefore preferable to super hydrophobic surface.
12. the device according to claim 1 for preparing microballoon, it is characterised in that the runner of the drop micro-fluidic chip The flow area size adjustable of at least part runner of system saves land setting.
13. the device according to claim 1 for preparing microballoon, it is characterised in that the action face is hydrophobic surface, Preferably super hydrophobic surface.
14. the device according to claim 13 for preparing microballoon, it is characterised in that the action face includes the collection The bottom wall in hole, the bottom wall for collecting hole is plane or lower concave curved surface.
15. the device according to claim 1 for preparing microballoon, it is characterised in that the manufacture module of collecting also includes row Liquid structure, the drainage structure are used to discharge the residual liquid in the collection hole.
16. the device according to claim 15 for preparing microballoon, it is characterised in that the drainage structure includes discharge opeing master Body, the discharge opeing main body include multiple collection holes, and multiple collection holes of the discharge opeing main body are used to receive the collection manufacture master The residual liquid is discharged after material in multiple collection holes of body.
17. the device for preparing microballoon according to claim 15 or 16, it is characterised in that the drainage structure includes setting Outage on the bottom wall in the collection hole and/or in side wall.
18. the device according to claim 17 for preparing microballoon, it is characterised in that the drainage structure includes being arranged on institute The outage in the side wall for collecting hole is stated, the drainage structure also includes tilting gearing, and the tilting gearing is used in discharge institute State and control the collection hole to be tilted towards the side wall side provided with the outage when collecting the residual liquid in hole.
19. the device according to claim 18 for preparing microballoon, it is characterised in that the control module fills with described tilt Coupling is put to control the tilting gearing to act.
20. the device for preparing microballoon according to claim 15 or 16, it is characterised in that the drainage structure also include pair The closeouts that the outage is blocked, the closeouts and the outage are detachably connected.
21. the device for preparing microballoon according to claim 15 or 16, it is characterised in that the drainage structure also includes true Empty aspirator, the vacuum suction apparatus are used to aspirate the residual liquid collected in hole by the outage.
22. the device according to claim 21 for preparing microballoon, it is characterised in that the control module is taken out with the vacuum Device coupling is inhaled to control the vacuum suction apparatus to act.
23. the device according to claim 1 for preparing microballoon, it is characterised in that the manufacture module of collecting also includes shaking Movable property generating apparatus, the generation device that rocks are used to make the manufacture main body of collecting produce the material balling-up made in the collection hole Rock.
24. the device according to claim 23 for preparing microballoon, it is characterised in that the control module and the rolling movable property Generating apparatus is coupled to control the generation device that rocks to act.
25. the device according to claim 1 for preparing microballoon, the manufacture main body of collecting is removably disposed.
26. the device according to claim 1 for preparing microballoon, the motion module includes chip motion device, the core Piece telecontrol equipment is used to control the drop micro-fluidic chip to move, output port and the miniflow of the drop formation module Chip synchronization motion is controlled, the control module is coupled with the chip motion device to control the chip motion device action.
27. the device according to claim 26 for preparing microballoon, it is characterised in that the chip motion device includes being used for Control chip level moving parts that the drop micro-fluidic chip moves in the horizontal plane and/or for controlling the drop micro- The Chip Vertical moving parts that fluidic chip moves along the vertical direction.
28. the device according to claim 1 for preparing microballoon, it is characterised in that the motion module includes bulk motion Device, the bulk motion device are used to control described collect to manufacture bulk motion, the control module and the bulk motion Device is coupled to control the bulk motion device action.
29. the device according to claim 28 for preparing microballoon, it is characterised in that the bulk motion device includes being used for Control and described collect the main body horizontal movement component that moves in the horizontal plane of manufacture main body and/or described collect manufacture for controlling The body normal moving parts that main body is moved along the vertical direction.
30. the device according to claim 29 for preparing microballoon, it is characterised in that the main body horizontal movement component includes Motion platform, the manufacture main body of collecting are removably attachable on the motion platform.
31. the device according to claim 1 for preparing microballoon, it is characterised in that the drop formation module also includes defeated Go out part, the entrance of the output block connects with the runner system, and the outlet of the output block forms the drop formation The output port of module.
32. the device according to claim 31 for preparing microballoon, it is characterised in that the outlet of the output block is fixed and set Put.
33. the device according to claim 31 for preparing microballoon, it is characterised in that the motion module includes being used to control The output block telecontrol equipment of the position of the outlet of the output block.
34. the device according to claim 33 for preparing microballoon, it is characterised in that the control module and the output section Part telecontrol equipment is coupled to control the output block telecontrol equipment to act.
35. the device according to claim 1 for preparing microballoon, it is characterised in that the device for preparing microballoon also includes Reagent memory module, the reagent memory module are used to store the material for forming the microballoon.
36. the device according to claim 35 for preparing microballoon, it is characterised in that the reagent memory module includes：

Core liquid memory space；And/or

Covering liquid memory space；And/or

Curing agent memory space；And/or

Cleaning fluid memory space；And/or

Continuous phase fluid memory space.
37. the device according to claim 36 for preparing microballoon, it is characterised in that

The first fluid entrance has connected state so that the drop micro-fluidic chip is used with the core liquid memory space In generating the core liquid drop, the control module also controls the core liquid drop accordingly to drop to the institute for collecting hole State in action face；And/or

The first fluid entrance has connected state so that the drop micro-fluidic chip is used with the covering liquid memory space In generation covering liquid drop, the control module controls each covering liquid drop accordingly to drop to the work for collecting hole With on surface；And/or

The first fluid entrance has connected state so that the drop micro-fluidic chip is used with the curing agent memory space In generation curing agent drop, the control module also controls each curing agent drop accordingly to drop to the described of the collection hole In action face.
38. the device according to claim 1 for preparing microballoon, it is characterised in that the device for preparing microballoon also includes First temperature control module, first temperature control module are used to control core liquid, covering liquid, curing agent, cleaning fluid and continuous phase fluid At least one of temperature.
39. the device for preparing microballoon according to claim 38, it is characterised in that the control module and the described first temperature Control module is coupled to control first temperature control module to act.
40. the device for preparing microballoon according to claim 38, it is characterised in that first temperature control module is included each other Independent multiple material structure of controlling temperature, the multiple material structure of controlling temperature include being used to control the core of the temperature of the core liquid Liquid structure of controlling temperature, the covering liquid structure of controlling temperature of temperature for controlling the covering liquid, the temperature for controlling the curing agent Curing agent structure of controlling temperature, temperature for controlling the cleaning fluid cleaning fluid structure of controlling temperature and for controlling the continuous phase At least one continuous phase fluid structure of controlling temperature of the temperature of fluid.
41. the device according to claim 1 for preparing microballoon, it is characterised in that the device for preparing microballoon also includes Second temperature control module, second temperature control module are used for the temperature for controlling the material in the collection hole.
42. the device according to claim 41 for preparing microballoon, it is characterised in that the control module and the described second temperature Control module is coupled to control second temperature control module to act.
43. the device according to claim 1 for preparing microballoon, it is characterised in that the device for preparing microballoon also includes Liquid relief module, the liquid relief module are used for instil at least one of covering liquid, curing agent and cleaning fluid.
44. the device according to claim 43 for preparing microballoon, it is characterised in that the control module and the liquid relief mould Block is coupled to control the liquid relief module action.
45. the device according to claim 43 for preparing microballoon, it is characterised in that the liquid relief module includes liquid-transfering gun, The device for preparing microballoon also includes replacing pipette tips storage module, and the replacement pipette tips storage module is used to store the liquid relief The replacement pipette tips of rifle.
46. according to the device for preparing microballoon described in claim 1, it is characterised in that the device for preparing microballoon also includes material Expect pretreatment module, the pretreatment module is used to enter to exercise core liquid and/or covering liquid to core liquid and/or covering liquid The pretreatment combined with collecting the orbicule in hole.
A kind of 47. method for preparing microballoon, it is characterised in that including：

Core liquid drop formation and collection step, including：Core liquid is passed through into drop micro-fluidic chip with by the drop Micro-fluidic chip generates core liquid drop；The core liquid drop is accordingly dropped to the different collection holes for collecting manufacture main body Action face on；

Microballoon generation step, including：Microballoon described in the core liquid droplet formation is based in the action face in the collection hole.
48. the method according to claim 47 for preparing microballoon, it is characterised in that the core liquid drop formation and collection Step also includes：Continuous phase fluid is passed through into the drop micro-fluidic chip so that the continuous phase fluid is described micro-fluidic Separate the core liquid in the runner system of chip to generate core liquid drop, the continuous phase fluid and the core liquid not phase It is molten.
49. the method according to claim 47 for preparing microballoon, it is characterised in that the continuous phase fluid is gas or liquid Body.
50. the method according to claim 47 for preparing microballoon, it is characterised in that the core liquid includes making by outside With the material that can be molded the core liquid.
51. the method according to claim 47 for preparing microballoon, it is characterised in that the microballoon generation step includes cladding Layer generation step, the clad generation step include：

Covering liquid drop formation and collection step, including generation covering liquid drop, and the covering liquid drop is accordingly dropped to In the action face in the different collection holes；

Encapsulation steps, including the covering liquid drop for making to drop in the action face are coated on outside the orbicule in the collection hole Side is to form clad.
52. the method according to claim 51 for preparing microballoon, it is characterised in that institute is generated by drop micro-fluidic chip State covering liquid drop；Or the covering liquid drop is generated by liquid relief module.
53. the method according to claim 51 for preparing microballoon, it is characterised in that the encapsulation steps also include rocking step Suddenly, the shaking step is included in form the clad during rock it is described collect manufacture main body so that it is described collect system Making main body and producing rocks the material balling-up in the collection hole.
54. the method according to claim 51 for preparing microballoon, it is characterised in that the microballoon generation step is included at least The clad generation step is performed twice.
55. the method according to claim 51 for preparing microballoon, it is characterised in that the covering liquid includes making by outside With the material that can be molded the covering liquid.
56. the method for preparing microballoon according to claim 47 or 55, it is characterised in that the external action includes temperature Control action, chemical action and/or biological respinse effect.
57. the method according to claim 47 for preparing microballoon, it is characterised in that the microballoon generation step includes solidification Step, the curing schedule include carrying out curing process to the orbicule in the collection hole.
58. the method according to claim 57 for preparing microballoon, it is characterised in that the curing process is including the use of solidification The orbicule in hole is collected in agent solidification；And/or the curing process includes the temperature of the control orbicule.
59. the method according to claim 58 for preparing microballoon, it is characterised in that solidified using curing agent and collected in hole The orbicule includes：Curing agent drop is generated, and the curing agent drop is accordingly dropped to the different collection holes In action face with solidify it is described collection hole in the orbicule.
60. the method according to claim 59 for preparing microballoon, it is characterised in that institute is generated by drop micro-fluidic chip State curing agent drop；Or the curing agent drop is generated by liquid relief module.
61. the method according to claim 47 for preparing microballoon, it is characterised in that the microballoon generation step also includes remaining Liquid removes step, and the extraction raffinate, which removes step, to be included removing the residual liquid collected in hole.
62. the method according to claim 61 for preparing microballoon, it is characterised in that the extraction raffinate, which removes step, includes cleaning Step, the cleaning step include cleaning fluid is added dropwise into the collection hole and form the residual liquid, and the cleaning fluid is The material of the orbicule cleaned in the collection hole.
63. the method according to claim 61 for preparing microballoon, it is characterised in that the extraction raffinate, which removes step, to be included to institute The residual liquid collected in hole is stated to be sucked by vacuum.
64. the method according to claim 47 for preparing microballoon, it is characterised in that the method for preparing microballoon also includes Material temperature rate-determining steps, the material temperature rate-determining steps include controlling the core liquid, covering liquid, curing agent, cleaning fluid With the temperature of at least one of continuous phase fluid.
65. the method according to claim 64 for preparing microballoon, it is characterised in that the material temperature rate-determining steps include It is independent at least one of the core liquid, the covering liquid, the curing agent, the cleaning fluid and described continuous phase fluid Ground carries out temperature control.
66. the method according to claim 47 for preparing microballoon, it is characterised in that the method for preparing microballoon also includes Pretreatment step, the pretreatment step include entering to exercise core liquid and/or cladding to core liquid and/or covering liquid The pretreatment that liquid is combined with collecting the orbicule in hole.
67. the method according to claim 47 for preparing microballoon, it is characterised in that perform the core liquid liquid at least twice Drop generation and collection step.
68. the method according to claim 47 for preparing microballoon, it is characterised in that the microballoon be single chondritic or It is layered chondritic.
69. the method according to claim 47 for preparing microballoon, it is characterised in that the microballoon is for biological 3D printing Biological prepared Chinese ink material, the microballoon includes cell.
70. the method according to claim 47 for preparing microballoon, it is characterised in that the method for preparing microballoon includes adopting The microballoon is prepared with the device for preparing microballoon according to any one of Claims 1-4 6.