CN205627904U

CN205627904U - Nucleocapsid structure preparation equipment

Info

Publication number: CN205627904U
Application number: CN201620283791.8U
Authority: CN
Inventors: 张雅雅; 左潇; 温学敏; 何俊轩; 李意军
Original assignee: Sichuan Revotek Biotechnology Co Ltd
Current assignee: Sichuan Revotek Biotechnology Co Ltd
Priority date: 2016-04-07
Filing date: 2016-04-07
Publication date: 2016-10-12
Anticipated expiration: 2026-04-07

Abstract

The utility model relates to a nucleocapsid structure preparation technical field, in particular to nucleocapsid structure preparation equipment. The utility model discloses a nucleocapsid structure preparation equipment includes: including dropping device and formation device, it includes at least one generation unit to generate the device, the generation unit has the effect surface, the effect surface is the hydrophobic surface, dropping device is arranged in instiling into the generation unit with nuclear material liquid and/or shell material liquid, effect surface make the independent shaping of nuclear material liquid be the globoid or make nuclear material liquid and generation unit in fashioned globoid combine further that the shaping is the globoid, the cladding of shell material liquid forms the shell and the further spheration body in the generation unit on the fashioned globoid in the generation unit. The utility model discloses ingenious favourable terrain carries out the shaping processing with the hydrophobicity characteristics on effect surface to the nuclear material liquid that instils into in the generation unit, can realize the effective control to nucleocapsid frame forming shape, guarantees that the nucleocapsid structure has better sphericity.

Description

Nucleocapsid structure Preparation equipment

Technical field

This utility model relates to nucleocapsid structure preparing technical field, particularly to a kind of nucleocapsid structure Preparation equipment.

Background technology

Nucleocapsid structure refer to filmogen by material capsules such as solid, liquid or gases in wherein institute's shape The microscopic, spherical structure of diameter 1～1000 μm become, wherein, the internal material loaded of nucleocapsid structure Material is referred to as core material (or claim core), and the wall film of outside encapsulation is then referred to as shell material (or referred to as wall Material).Biological brick (also known as biological prepared Chinese ink) is that one is applied to biometric print (as 3D is biological Printing field), organizational project, the nucleocapsid structure in the field such as regenerative medicine, due to biometric print Biological tissue and organ that technology produces are required to have certain biological function, therefore, make For the biological brick of biological printed material generally to wrap celliferous collagen solution as core material liquid, The structure being additionally, since biological tissue and organ is the finest, therefore, and the particle diameter of biological brick Less than general nucleocapsid structure, it usually needs to control between 10～200 μm, and size Required precision is the highest.

Prior art still use traditional biochemical room laboratory hand preparation technology to prepare core Shell structure, the preparation method of most common of which is orifice method.Orifice method generally by core material liquid and Shell material liquid is dissolved in same solution, then by the dropper being loaded with nucleocapsid mixed solution Or the dropper such as syringe applies vibration or potential pulse and nucleocapsid mixed solution is instilled solidification In agent, nucleocapsid mixed solution solidifies rapidly in firming agent thus forms nucleocapsid structure.

Correspondingly, existing nucleocapsid structure apparatus for preparation, it is generally also and prepares based on orifice method Nucleocapsid structure, it include vibrate (or pulse) bringing device, dropper and be arranged on drip Reaction vessel below liquid device, is contained with firming agent in reaction vessel, dropper is then shaking Under the effect of dynamic (or pulse) bringing device, nucleocapsid mixed solution is instilled in reaction vessel, drip The nucleocapsid mixed solution entered in reaction vessel solidify to form nucleocapsid structure under the effect of firming agent, Wherein, vibration (or pulse) bringing device is by the flow channel to the solution in dropper Position applies the vibration of certain frequency and certain amplitude makes solution jet break to form default grain The drop of footpath size.

Inventor studies discovery, existing nucleocapsid structure preparation method and apparatus for preparation by analysis The problem that there are following several respects:

(1) forming shape of nucleocapsid structure it is difficult to control to.Nucleocapsid is prepared based on prior art During structure, nucleocapsid mixed solution directly instills in firming agent and solidifies, the shape of stratum nucleare and shell The shape of layer is all to rely on each self chemical reaction to be formed in the curing process, and not Being controlled by the forming shape of stratum nucleare and shell, therefore, the forming shape of stratum nucleare and shell is difficult To be effectively controlled, the forming shape randomness of stratum nucleare and shell is relatively big, the sphericity of stratum nucleare Poor, the sphericity of the shell being coated on stratum nucleare is the most poor, so that the nucleocapsid ultimately formed The molding effect of structure is unsatisfactory.The shape being additionally, since stratum nucleare is dependent on self chemistry instead Should be formed, this most just requires that core material liquid has self and is prone to be shaped to spherical feature, from And the range of choice of available core material liquid in prior art is restricted, some not easy-formations Then it is difficult by prior art preparation for spherical material and forms satisfactory nucleocapsid structure, and This also results in prior art and is difficult to the preparation of some nucleocapsid structure, so that certain can be hindered The development of a little particular technology areas, such as, collagen need under given conditions could molding, base It is difficult by collagen in prior art and is directly prepared into nucleocapsid structure..

(2) vibration or pulse separatory easily affect the performance of nucleocapsid structure.In prior art Separatory is carried out, owing to vibration or potential pulse can affect core material liquid by vibratory drilling method or impulse method With the performance of shell material liquid, therefore, carrying out separatory by vibratory drilling method can affect the property of nucleocapsid structure Can, particularly with the have specific characteristics nucleocapsid structure that can require, such as core material with having biological living Property the nucleocapsid structure of cell, the adverse effect of vibration or pulse separatory method is more prominent.

(3) particle diameter of the nucleocapsid structure prepared is bigger.Prior art use dropper or Syringe drips, and each dripping quantity is more, and drop size is relatively big, and due to nucleocapsid structure Particle diameter directly related with solution dripping quantity, therefore, the particle diameter of preparation-obtained nucleocapsid structure The biggest, generally more than 500 μm, and just as it was previously stated, some technical field requires nucleocapsid Structure has less grain size, and such as, biometric print technical field requires the grain of biological brick Footpath controls between 10～200 μm, it is seen then that prior art is difficult to meet the technology such as biometric print The field requirement to nucleocapsid structure particle diameter.

(4) scale error of the nucleocapsid structure prepared is bigger, it is difficult to ensure nucleocapsid knot The dimensional accuracy of structure.Prior art use dropper or syringe realize core material liquid and shell material The absorption of liquid and dropping, on the one hand, owing to dropper and syringe all cannot accurately and in real time React its amount of solution drawn, accordingly, it is difficult to it is molten to ensure that dropper and syringe are drawn every time Hydroful foot preparation requirement；On the other hand, dropper and syringe are also difficult to control to each dripping quantity Precision, therefore, prior art is difficult to ensure that the dimensional accuracy of nucleocapsid structure, and this not only results in During dropping, actual dripping quantity is different from default dripping quantity every time, the actual particle size of single nucleocapsid structure Relatively big with predetermined size error, and will also result in and be difficult to ensure that repeatedly, repeat component and titrated The accuracy of journey, both cannot ensure the concordance of not homogeneous dripping quantity, and it is the most right to meet The coherence request of different IPs shell structure particle diameter, it is also difficult to ensure that homogeneous dripping quantity is according to presetting Difference is changed, and meets the diversity requirement in some cases to particle diameter, such as, based on existing Technology is had just to be difficult to prepare the nucleocapsid structure with multilamellar different-thickness shell.

Visible, existing nucleocapsid structure preparation method and apparatus for preparation be difficult to meet include biological brick Deng the preparation requirement of nucleocapsid structure, have that forming shape is the best, particle diameter is relatively big, dimensional accuracy relatively The defect such as poor, inefficient, but also there is the problem easily damaging biological brick cytoactive.

Utility model content

One to be solved in the utility model technical problem is that: existing nucleocapsid structure Preparation equipment It is difficult to control to the forming shape of nucleocapsid structure.

In order to solve above-mentioned technical problem, this utility model provides a kind of nucleocapsid structure preparation and sets Standby, it includes dropper and generating means, and generating means includes at least one signal generating unit, Signal generating unit has action face, and action face is hydrophobic surface, and dropper is for by core Material liquid and/or shell material liquid instill in signal generating unit, and action face makes core material liquid separately formed For spheroid or make core material liquid in type spheroid in signal generating unit be combined further one-tenth Type is spheroid, and shell material liquid is coated in signal generating unit and forms shell in type spheroid And in signal generating unit, form spheroid further.

Alternatively, action face is plane, or, action face includes lower concave curved surface.

Alternatively, signal generating unit is flat board, and action face is the plate face of flat board；Or, generate Unit is the chamber of top end opening, and the diapire of chamber is plane or includes lower concave curved surface, makees It is the diapire of chamber with surface.

Alternatively, lower concave curved surface is U-shaped or ball crown type.

Alternatively, generating means includes at least two signal generating unit, at least two signal generating unit that This is arranged in generating means isolator.

Alternatively, nucleocapsid structure Preparation equipment also includes rocking device, rocks device at core Material liquid or shell material liquid cladding signal generating unit make generation list during in type spheroid It is in type spherical that unit's generation can make core material liquid or shell material liquid be uniformly wrapped in signal generating unit Rocking on body.

Alternatively, generating means also includes drainage structure, and drainage structure is used for discharging formation nucleocapsid Remaining liq in signal generating unit after structure.

Alternatively, signal generating unit is the chamber of top end opening, and the diapire of chamber is action face, Wherein, drainage structure is arranged on the diapire of chamber；Or, drainage structure is arranged on chamber On sidewall.

Alternatively, drainage structure is arranged on the sidewall of chamber, and nucleocapsid structure Preparation equipment is also Including incline controller, incline controller is single for generating after discharging formation nucleocapsid structure The signal generating unit sidewall side being provided with drainage structure towards chamber is controlled during remaining liq in unit Tilt.

Alternatively, drainage structure includes the outage connected with signal generating unit.

Alternatively, drainage structure also includes the closeouts blocking outage, closeouts with Outage is detachably connected.

Alternatively, dropper includes liquid distributing device and at least one suction nozzle, and suction nozzle can be drawn Core material liquid and/or shell material liquid, liquid distributing device includes that compressed air is filled with portion and at least one is used In the suction nozzle installation portion of installation suction nozzle, the compressed air portion of being filled with passes through suction nozzle installation portion in suction nozzle It is filled with compressed air the core material liquid in suction nozzle or shell material liquid dispersion to be become the liquid of predetermined size Instill in signal generating unit.

Alternatively, the inwall of suction nozzle is at least for dripping core material liquid and/or the dropping of shell material liquid The part of end is hydrophobic surface.

Alternatively, dropper also includes that uptake test section, uptake test section are used for detecting Core material liquid that suction nozzle is drawn or the uptake of shell material liquid.

Alternatively, the uptake scalable of core material liquid and/or shell material liquid.

Alternatively, dropper includes at least two suction nozzle, at least two suction nozzle at least one Individual for drawing core material liquid, at least two suction nozzle at least one be used for drawing shell material liquid.

Alternatively, liquid distributing device includes at least two suction nozzle installation portion, and at least two suction nozzle is installed Distance between portion can regulate.

Alternatively, suction nozzle is removably installed on suction nozzle installation portion.

Alternatively, nucleocapsid structure Preparation equipment also includes suction nozzle storage module, suction nozzle storage module For depositing suction nozzle.

Alternatively, nucleocapsid structure Preparation equipment also includes displacement drive, displacement drive For controlling the relative motion of dropper and signal generating unit.

Alternatively, nucleocapsid structure Preparation equipment also includes device for storing liquid, and device for storing liquid at least includes First liquid storage space and the second liquid storage space, the first liquid storage space is used for storing core material liquid, the Two liquid storage spaces are used for storing shell material liquid.

Alternatively, device for storing liquid also includes that the 3rd liquid storage space, the 3rd liquid storage space are used for storing Cleanout fluid；And/or, device for storing liquid also includes that the 4th liquid storage space, the 4th liquid storage space are used for storing up Deposit firming agent.

Alternatively, nucleocapsid structure Preparation equipment also includes temperature control module, and temperature control module is used for controlling Core material liquid and/or the temperature of shell material liquid.

Alternatively, temperature control module includes that the first temperature control module, the first temperature control module are used for controlling life Become the temperature of unit so that the temperature of signal generating unit can be with core material liquid and/or shell material liquid institute The temperature needed keeps consistent；And/or, nucleocapsid structure Preparation equipment also includes device for storing liquid, storage Liquid device at least includes the first liquid storage space and the second liquid storage space, and the first liquid storage space is used for storing up Depositing core material liquid, the second liquid storage space is used for storing shell material liquid, and temperature control module includes the second temperature Control module, the second temperature control module is for controlling the temperature of device for storing liquid so that the temperature of device for storing liquid Can with core material liquid and/or shell material liquid required for temperature keep consistent.

Alternatively, nucleocapsid structure Preparation equipment also includes pretreatment device, pretreatment Device for carry out core material liquid and/or shell material liquid making core material liquid or shell material liquid with The pretreatment that in signal generating unit, in type spheroid combines.

Alternatively, pretreatment device is by making core material liquid and/or shell material liquid and generating list Opposite charges in type spheroid band in unit.

Alternatively, nucleocapsid structure Preparation equipment is biological active microsphere Preparation equipment.

Alternatively, hydrophobic surface is super hydrophobic surface.

Nucleocapsid structure Preparation equipment of the present utility model, it utilizes the hydrophobicity feature of action face Being shaped processing to the core material liquid instilled in signal generating unit, it is spherical for making core material liquid molding Body, can not only ensure the sphericity of stratum nucleare, and it is the most right to also allow for shell material liquid Spheroid wraps up, and spheroid can intactly be wrapped up by shell material liquid, from And ensure that the final nucleocapsid structure prepared has more preferable sphericity.Visible, of the present utility model Nucleocapsid structure Preparation equipment, controls the ball of spheroid by the hydrophobicity feature utilizing action face Shape degree, it is possible to realize the control to nucleocapsid structure forming shape so that nucleocapsid structure has more preferably Sphericity.

By referring to the drawings exemplary embodiment of the present utility model being described in detail, Further feature of the present utility model and advantage thereof will be made apparent from.

Accompanying drawing explanation

In order to be illustrated more clearly that this utility model embodiment or technical scheme of the prior art, under The accompanying drawing used required in embodiment or description of the prior art will be briefly described by face, aobvious and Easily insight, the accompanying drawing in describing below is only embodiments more of the present utility model, for ability From the point of view of the those of ordinary skill of territory, on the premise of not paying creative work, it is also possible to according to this A little accompanying drawings obtain other accompanying drawing.

Fig. 1 a illustrates that drop instills the forming shape schematic diagram on hydrophilic surface.

Fig. 1 b illustrates that drop instills the forming shape schematic diagram on hydrophobic surface.

Fig. 2 illustrates that the structure of the nucleocapsid structure Preparation equipment of this utility model first embodiment is shown It is intended to.

Fig. 3 illustrates the top view of the orifice plate in embodiment illustrated in fig. 2 as generating means.

Fig. 4 illustrates the structural representation of blind hole when diapire is U-shaped, and be shown through based on This blind hole dropping different capabilities question response liquid forms showing of the process of different predetermined size spheroid It is intended to.

Fig. 5 illustrates the structural representation that diapire is blind hole during plane, and is illustrated based on this blind hole The signal of the process of different predetermined size spheroid is formed by dropping different capabilities question response liquid Figure.

Fig. 6 illustrates have monolayer stratum nucleare and the nucleocapsid structure of double-deck shell.

Fig. 7 illustrates have double-deck stratum nucleare and the nucleocapsid structure of monolayer shell.

Fig. 8 illustrates have double-deck stratum nucleare and the nucleocapsid structure of double-deck shell.

In figure:

1, dropper；11, liquid distributing device；12, suction nozzle；

2, orifice plate；21, blind hole；211, action face；

3, suction nozzle storage module；

43, XYZ motion module；

51, the first temperature control module；511, soaking plate；52, the second temperature control module；

6, device for storing liquid；61, the first liquid storage space；62, the second liquid storage space；

7, base；71, the first base plate；72, the second base plate；

8, bracing frame；

9, device is controlled.

Detailed description of the invention

Below in conjunction with the accompanying drawing in this utility model embodiment, in this utility model embodiment Technical scheme is clearly and completely described, it is clear that described embodiment is only this practicality Novel a part of embodiment rather than whole embodiments.Below at least one exemplary reality The description only actually executing example is illustrative, never as to this utility model and application thereof Or any restriction used.Based on the embodiment in this utility model, ordinary skill people The every other embodiment that member is obtained under not carrying out creative work premise, broadly falls into this reality By novel protected scope.

May not make in detail for technology, method and apparatus known to person of ordinary skill in the relevant Thin discussion, but in the appropriate case, described technology, method and apparatus should be considered to authorize to be said A part for bright book.

In description of the present utility model, it is to be understood that the noun of locality as " forward and backward, upper, Under, left and right ", indicated by " laterally, vertical, vertical, level " and " top, the end " etc. Orientation or position relationship be normally based on orientation shown in the drawings or position relationship, merely to It is easy to describe this utility model and simplify description, in the case of illustrating on the contrary, these sides Position word do not indicate that and imply the device of indication or element must have specific orientation or with Specific azimuth configuration and operation, therefore it is not intended that limit to this utility model protection domain System；The noun of locality " inside and outside " refers to inside and outside the profile relative to each parts itself.

In description of the present utility model, it is to be understood that use " first ", " second " Parts are limited, it is only for be easy to corresponding parts be distinguished, as not having Deng word Stated otherwise, above-mentioned word is had not to have particular meaning, therefore it is not intended that new to this practicality The restriction of type protection domain.

In description of the present utility model, " nucleocapsid structure " refer to utilize filmogen by solid, Liquid or gas are encapsulated in the structure formed in it, wherein, claim for forming the material of stratum nucleare For core material, and it is referred to as shell material for forming the material of the shell of outside encapsulation.

As used herein, term " biological brick " is for referring to by core of the present utility model A kind of elementary cell that shell structure Preparation equipment builds, it can be used for multiple field, such as biological Print the fields such as (such as 3D biometric print), organizational project, regenerative medicine.Preferably, this reality The structure and composition can having with novel biological brick is: wrap celliferous stratum nucleare, wherein, Cell can carry out growing, breed, break up or migrating, and stratum nucleare is made up of Biodegradable material, And for the material needed for the vital movement offer of cell；With, the shell of encapsulation stratum nucleare, shell It is positioned at outside, is made up of Biodegradable material, and provide power for internal stratum nucleare and cell Learn protection, the base unit that the biological brick of this preferred structure can print as biological 3D. Biology is shown as based on the nucleocapsid structure prepared by nucleocapsid structure preparation method of the present utility model Active microsphere.

In some embodiment of the present utility model, the stratum nucleare of biological brick wraps up one or more Cell, the most one or more cells, such as 1-10⁶Individual cell, 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 cell.

Some preferred embodiment in, the nucleocapsid structure prepared by equipment of the present utility model (such as biological brick) is solid or semisolid.At some other preferred embodiment in, this Nucleocapsid structure (such as biological brick) prepared by the equipment of utility model is gel state, such as, The stratum nucleare of the nucleocapsid structure (such as biological brick) prepared by equipment of the present utility model and/or shell Layer can be gel state.Some preferred embodiment in, equipment of the present utility model is made Standby nucleocapsid structure (such as biological brick) comprises hydrogel.Some preferred embodiment in, Hydrogel comprises alginate, agarose, gelatin, chitosan or other water solublity or hydrophilic Polymer.

Fig. 2-5 respectively illustrates the nucleocapsid structure Preparation equipment of two embodiments of this utility model Structural representation.Reference Fig. 2-5, nucleocapsid structure Preparation equipment provided by the utility model, Including dropper 1 and generating means, wherein, generating means includes at least one signal generating unit, Signal generating unit has action face 211, and action face 211 is hydrophobic surface, dropper 1 for instilling core material liquid and/or shell material liquid in signal generating unit, and action face 211 Make core material liquid separately formed for spheroid or make core material liquid molded with signal generating unit Spheroid to be incorporated into one-step shaping be spheroid, shell material liquid is coated in signal generating unit to become Shell is formed to form spheroid in signal generating unit further on the spheroid of type.

Nucleocapsid structure Preparation equipment of the present utility model make use of the spy of hydrophobic surface dexterously Point, is set to hydrophobic surface by the action face 211 of signal generating unit so that by dropper The 1 core material liquid first instilled in signal generating unit can be shaped to spherical or ellipsoid shape, and formation has The spheroid of good sphericity, it is simple to the rear shell solution instilled in signal generating unit uniformly and can be expected It is wrapped up by ground, and spheroid can intactly be wrapped up by shell material liquid, shape Become there is the nucleocapsid structure of preferable sphericity.Visible, nucleocapsid structure of the present utility model preparation sets Standby, the sphericity of spheroid is controlled by the hydrophobicity feature utilizing action face 211, it is possible to Realize the control to nucleocapsid structure forming shape so that nucleocapsid structure has more preferable sphericity. And, in the case of spheroid is wrapped up in action face 211 by shell material liquid, make Also shell material liquid can be played certain molding effect with surface 211 such that it is able to change further The sphericity of kind nucleocapsid structure.

Action face of the present utility model can be plane, and such as, signal generating unit is flat board, makees With the plate face that surface 211 is this flat board；Or, signal generating unit be top end opening chamber (as It is a beaker), and the diapire of this chamber is plane, action face 211 is the diapire of this chamber. In this case, nucleocapsid structure Preparation equipment utilizes the hydrophobicity of action face 211 or super thin Aqueous feature controls the forming shape of nucleocapsid structure.

But preferably, action face 211 of the present utility model includes lower concave curved surface, such as, Under signal generating unit is the chamber (as a beaker) of top end opening, and the diapire of this chamber includes Concave curved surface, action face 211 is the diapire of this chamber.Owing to lower concave curved surface can produce Make core material liquid and shell material liquid to the guide effect of center convergence, so can not only make core material Liquid and shell material liquid are easier to be shaped to spherical or ellipsoid shape, make nucleocapsid structure have preferably Sphericity, and, make shell material liquid to center convergence it is also possible that core material liquid and/or shell material Liquid is more rapid and is coated on fully on spheroid, improves parcel efficiency, and improves further Parcel effect.Visible, in this case, nucleocapsid structure Preparation equipment is possible not only to utilize to be made Control the forming shape of nucleocapsid structure by the hydrophobicity feature on surface 211, but also can utilize The guide effect of converging of lower concave curved surface improves the sphericity of nucleocapsid structure further, and further Improve core material liquid and/or the shell material liquid parcel efficiency to spheroid.It is highly preferred that lower concave curved U-shaped or the ball crown type of face.

Signal generating unit of the present utility model can be one or at least two, but in order to carry further High preparation efficiency, signal generating unit is preferably at least two, this at least two signal generating unit each other every Liftoff being arranged in generating means, such nucleocapsid structure Preparation equipment can complete multiple core simultaneously The preparation of shell structure such that it is able to save preparation time, improves preparation efficiency.Additionally, each Signal generating unit is isolated from each other, additionally it is possible to ensure the independence of each nucleocapsid structure preparation process, and one Aspect, relative to simultaneously prepare the situation of multiple nucleocapsid structure in same signal generating unit, due to The preparation of each nucleocapsid structure no longer interferes, and therefore can ensure that the property of each nucleocapsid structure Can not be affected by other nucleocapsid structures；On the other hand, each nucleocapsid structure preparation process is mutual Independent, as shown in Figure 4 and Figure 5, also allow for by controlling dripping quantity in each signal generating unit Difference is prepared while realizing different-grain diameter nucleocapsid structure, even, and can be by raw at each Become in unit and drip different core material liquid or shell material liquid to realize variety classes nucleocapsid structure While prepare so that nucleocapsid structure Preparation equipment of the present utility model disclosure satisfy that more The preparation demand of sample；Another further aspect, owing to each signal generating unit is isolated from each other, therefore, even if Rock generating means, also do not result in interfering of each signal generating unit, so that Shell material liquid is made more by rocking signal generating unit during shell material liquid cladding spheroid Being coated on equably on spheroid, this rocking manually can be rocked by operator, but preferably Ground, can arrange in nucleocapsid structure Preparation equipment of the present utility model and rock device, by this Rock device to realize required rocking, namely this rocks device at shell material liquid coated ball Signal generating unit is made to produce the rolling that shell material liquid can be made to be uniformly wrapped on spheroid during shape body Dynamic, to improve the molding effect of nucleocapsid structure further.

Nucleocapsid structure has been prepared it is possible to there is residual liquid in rear signal generating unit, the most Remaining shell material liquid, cleanout fluid or firming agent etc., it is of course possible to utilize sponge or other be similar to Absorbent material residual liquid is discharged, but so that residual liquid can be by cleaner row Going out and make the process to these residual liquids convenient, this utility model is preferably by arranging Residual liquid is discharged by drainage structure, and as a kind of embodiment, drainage structure includes and generates The outage of unit connection, further, drainage structure also includes blocking outage Closeouts, closeouts is detachably connected with outage, has so prepared when nucleocapsid structure After when needing remaining liq is processed, only closeouts need to be pulled down from outage and make residue Liquid flows out from outage, and again closeouts is blocked after remaining liq is got rid of totally With on outage, can ensure that again being smoothed out of nucleocapsid structure preparation process, facilitate and be prone to Realize.When the chamber that signal generating unit is aforesaid top end opening, and action face 211 is this chamber During the diapire of room, drainage structure can be arranged on the diapire of this chamber, or, drainage structure Can also be arranged on the sidewall of this chamber, in such a case, it is possible to arrange inclination control dress Put, this incline controller remaining in signal generating unit after needing to discharge formation nucleocapsid structure The signal generating unit sidewall lopsidedness being provided with drainage structure towards chamber is controlled during remaining liquid, this Sample can either ensure the convenient discharge of redundant solution, can avoid again because arranging drainage structure and shadow Ring the preparation of nucleocapsid structure, it is particularly possible to avoid drainage structure to affect core material liquid in action face Molding effect on 211.

In order to avoid prior art using vibration or pulse bringing device carry out separatory and caused Infringement nucleocapsid structure performance problem, dropper 1 of the present utility model can include separatory Device 11 and at least one suction nozzle 12, suction nozzle 12 can draw core material liquid and/or shell material liquid Body, liquid distributing device 11 includes that compressed air is filled with portion and at least one is for installing suction nozzle 12 Suction nozzle installation portion, the compressed air portion of being filled with is filled with pressure by suction nozzle installation portion in suction nozzle 12 Contracting air to become the drop of predetermined size by the core material liquid in suction nozzle 12 or shell material liquid dispersion Instill in signal generating unit.The liquid distributing device 11 of this dropper 1 passes through compressed air by core material Liquid or shell material liquid dispersion become the drop of predetermined size, it is achieved compressed air separatory method, by In vibration of the prior art or pulse bringing device need not be utilized core material liquid and shell material liquid Body applies vibration, therefore, it can be prevented effectively from the infringement nucleocapsid caused because of vibration separatory mode The problem of structural behaviour, contains the core material liquid such as collagen of cell, compression sky particularly with inside Edema caused by disorder of QI liquid mode can significantly reduce the infringement to cytoactive, meets the fields pair such as biometric print The bioactive requirement of nucleocapsid structure.And, by employing, there is compressed air and be filled with portion Liquid distributing device 11, it is less that nucleocapsid structure Preparation equipment of the present utility model can prepare particle diameter Nucleocapsid structure, can meet the requirement to particle diameter of the biometric print field, and can accurately and in real time The amount of solution that ground control is drawn, and can more accurately control the precision of each dripping quantity, have Effect reduces scale error, can either meet the coherence request to particle diameter, it is also possible to meet grain The diversity requirement in footpath.

Dropper 1 of the present utility model, including at least one suction nozzle 12, namely dropper 1 can include a suction nozzle 12 or at least two suction nozzle 12.Wherein, for dropper 1 situation only including a suction nozzle 12, this suction nozzle 12 is both used for drawing core material liquid, uses again In drawing shell material liquid, namely it needs successively to draw core material liquid and shell material liquid, this In the case of, in order to avoid interfering of core material liquid and shell material liquid, complete core material liquid After titration and before starting to draw shell material liquid, need by cleaning the modes such as suction nozzle 12 Being purged core material liquid remaining in suction nozzle 12, this not only results in preparation process more Complexity, also results in preparation efficiency relatively low.In order to solve this problem, dropping liquid of the present utility model Device 1 preferably includes at least two suction nozzle 12, in this at least two suction nozzle 12 at least one For draw in core material liquid, and this at least two suction nozzle 12 at least one be used for drawing shell Material liquid, namely use different suction nozzles 12 respectively core material liquid and shell material liquid to be inhaled Take such that it is able to be prevented effectively from interfering of core material liquid and shell material liquid, and make complete Nucleation material liquid titration after and start suction nozzle 12 cleaning step drawn before shell material liquid Can omit, and then can effectively simplify and utilize this nucleocapsid structure Preparation equipment to prepare nucleocapsid structure Operating procedure, improve preparation efficiency.It is highly preferred that dropper 1 includes multiple suction nozzle 12, a portion suction nozzle 12 is used for drawing core material liquid, simultaneously another part suction nozzle 12 For drawing shell material liquid, and when preparation process also needs to other solution such as use cleanout fluid Time, it is also possible to utilize single a part of suction nozzle 12 for drawing other solution such as cleanout fluid, The most both made every kind of solution all be drawn by special suction nozzle 12, it is to avoid different solutions it Between interfere, can reduce again the cleaning frequency of suction nozzle 12 in preparation process, improve system Standby efficiency.

So that the uptake of suction nozzle 12 is more accurate, dropper 1 of the present utility model Also including uptake test section, this uptake test section can detect the core that suction nozzle 12 is drawn Material liquid or the amount of shell material liquid, so can ensure that drawn solution dosage meets preparation and wants Ask, in order to avoid affect being smoothed out of nucleocapsid structure preparation process because uptake is too little or too much. In the present embodiment, core material liquid and/or the uptake of shell material liquid, can detect according to uptake Portion's feedback regulation.The nucleocapsid structure less in order to prepare particle diameter, suction nozzle 12 of the present utility model The rifle header structures such as the long glass capillary that internal diameter can also be used to be 130 μm or draw point, based on this Plant the suction nozzle 12 of rifle header structure, it is possible to achieve the dropping of tens of nl level drops, generate particle diameter more Little nucleocapsid structure, such as, uses the micro-sampling pin minimum of 0.1 μ l can titrate 0.05 μ l's Liquid measure (SGE, tapered), generating size is the nucleocapsid structure of about 300um.Can See, based on dropper 1 of the present utility model, it is possible to the nucleocapsid structure that prepared particle diameter is less, The requirement to particle diameter of the biometric print field can be met, and can control accurately and real-time to draw Amount of solution, and can more accurately control the precision of each dripping quantity, effectively reduce size Error, can either meet the coherence request to particle diameter, it is also possible to meet the diversity to particle diameter Requirement.

And, with action face 211 similarly, the inwall of suction nozzle 12 is at least used for dripping core The part of the dropping end of material liquid and/or shell material liquid is it can also be provided that hydrophobic surface, also I.e. suction nozzle 12 whole inwall or only suction nozzle 12 titration end inwall could be arranged to hydrophobic Property surface, by this set, can be prevented effectively from drip timed liquid to suction nozzle 12 inwall Stick so that titration process is easier to realize, and improves titration efficiency, but also is possible to prevent core Material liquid and the shell material liquid unnecessary residual in suction nozzle 12, is further ensured that dropping liquid fills Put the sensitivity of 1.

Additionally, the replacing of suction nozzle 12 and cleaning for convenience, in this utility model, suction nozzle 12 are removably installed on suction nozzle installation portion, so when needs suction nozzle 12 is replaced or During cleaning, can easily suction nozzle 12 be taken off.Based on this, nucleocapsid of the present utility model is tied Structure Preparation equipment can also include that suction nozzle storage module 3, suction nozzle storage module 3 are used for depositing suction 12, owing to depositing in unified for suction nozzle 12 in this suction nozzle storage module 3, therefore, it is possible to side Just the centralized management of suction nozzle 12, and ensure picking and placeing in order of suction nozzle 12, fill particularly with dropping liquid Put 1 situation including multiple suction nozzle 12, can divide different in suction nozzle storage module 3 Storage area, to realize being used for depositing drawing the suction nozzle 12 of core material liquid, for drawing shell material The subregion of the suction nozzle 12 of liquid and the suction nozzle 12 for drawing cleanout fluid or firming agent is deposited Put, be prevented effectively from and there is the suction nozzle 12 of different purposes mutually obscure.

Liquid distributing device 11 of the present utility model can only include a suction nozzle installation portion or include At least two suction nozzle installation portion, the most preferably, liquid distributing device 11 includes at least two suction nozzle Multiple signal generating units so can be dripped, it is ensured that can prepare by installation portion simultaneously simultaneously Multiple nucleocapsid structures so that preparation efficiency is effectively improved；Further, this at least two Suction nozzle installation portion is set to distance each other and can regulate, and so can meet different generation Different interval requirement between unit, improves titration efficiency, it is ensured that titration effect.

Draw corresponding liquid for the ease of suction nozzle 12, prepared by nucleocapsid structure of the present utility model Equipment can also include device for storing liquid 6, and at least needs due to this utility model to use core material liquid Body and shell material liquid, this device for storing liquid 6 at least includes the first liquid storage space 61 and the second liquid storage Space 62, wherein, the first liquid storage space 61 is used for storing core material liquid, the second liquid storage space 62 are used for storing shell material liquid, wherein the first liquid storage space 61 and the second liquid storage space 62 Quantity can increase and decrease according to the stratum nucleare of nucleocapsid structure and the kind of shell and quantity.Based on This, when core material liquid drawn by needs, only need to control suction nozzle 12 and move to the first liquid storage space Carry out at 61 drawing, and when shell material liquid drawn by needs, then control suction nozzle 12 and move Draw to the second liquid storage space 62, owing to being provided with different storages for different solution Liquid space, therefore can be prevented effectively from obscuring of different solutions so that the absorption of suction nozzle 12 is more Add convenient and swift.Certainly, when preparation process also needs to use firming agent and/or cleanout fluid, Device for storing liquid 6 can also include the 3rd liquid storage space and/or the 4th liquid storage space, wherein, Three liquid storage spaces are used for storing cleanout fluid, and the 4th liquid storage space is then used for storing firming agent.This reality Can include multiple independent container with novel device for storing liquid 6, each of which container becomes One independent liquid storage space；Or, device for storing liquid 6 can also be one and have multiple liquid storage The entirety in space, such as, can be a porous material test kit, the most each Kong Weiyi storage Liquid space.

Additionally, nucleocapsid structure Preparation equipment of the present utility model can also include temperature control module, temperature Control module is for controlling core material liquid and/or the temperature of shell material liquid, and such as, temperature control module can To include the first temperature control module 51, this first temperature control module 51 is for controlling the temperature of signal generating unit Degree so that signal generating unit temperature can with core material liquid and/or shell material liquid required for temperature Keep consistent；The most such as, when nucleocapsid structure Preparation equipment is provided with aforementioned device for storing liquid 6, Temperature control module can include the second temperature control module 52, and this second temperature control module 52 is used for controlling storage The temperature of liquid device 6 is so that the temperature of device for storing liquid 6 can be with core material liquid and/or shell material liquid Temperature required for body keeps consistent.

In order to make shell material liquid and/or shell material liquid preferably be coated on spheroid, this practicality Novel nucleocapsid structure Preparation equipment can also include pretreatment device, this pretreatment Device for carry out core material liquid and/or shell material liquid making core material liquid or shell material liquid with The pretreatment that in signal generating unit, in type spheroid combines, pre-through pretreatment device Processing, shell material liquid and/or shell material liquid can preferably be incorporated in signal generating unit molded Vesicle surface, spheroid is coated with.Core material liquid or shell material liquid and spheroid In conjunction with, can be by making the modes such as material liquid or shell material liquid and opposite charges on spheroid band Realize.Based on this, as a kind of embodiment of pretreatment device, pretreatment fills Putting can be by making core material liquid or shell material liquid and in type spheroid band in signal generating unit Upper opposite charges, such shell material liquid and/or shell material liquid can between opposite charges mutually It is adsorbed on spheroid under the effect of captivation, simple in construction, and is easily achieved.

In this utility model, nucleocapsid structure Preparation equipment can also include displacement drive, This displacement drive, for controlling the relative motion of dropper 1 and signal generating unit, so may be used To ensure that dropper 1 is capable of the accurate titration to signal generating unit.

Based on nucleocapsid structure Preparation equipment of the present utility model, can prepare with following nucleocapsid structure Method prepares nucleocapsid structure, and this nucleocapsid structure preparation method includes following step:

Core material liquid titration step: core material liquid is instilled the generation list with action face 211 In unit, action face 211 is hydrophobic surface so that core material liquid is at the work of action face 211 Separately formed under with become for spheroid or under the effect of action face 211 with signal generating unit It is spheroid that the spheroid of type is incorporated into one-step shaping；With

Shell material liquid titration step: shell material liquid is instilled in signal generating unit, so that shell material liquid Be coated in signal generating unit in type spheroid formed shell and in signal generating unit further Form spheroid shell material liquid titration step.

Liquid instills after the surface of solids, through the cutting of liquid-vapor interface of solid-liquid-gas three-phase point of intersection Angle between line and solid-liquid boundary line is contact angle, and contact angle is the biggest, then the surface of solids is thin Aqueous is the strongest, and the liquid instilling this surface of solids is also easier to form spheroid.According to contact angle Difference, the surface of solids can be divided into hydrophilic surface, hydrophobic surface and super-hydrophobicity table Face, wherein, hydrophilic surface refers to that contact angle is less than the surface of solids of 90 °, such as Fig. 1 a institute Showing, when liquid instills hydrophilic surface, it cannot be shaped to spherical, but " lying prone " is solid On surface, in flat；Hydrophobic surface refers to that contact angle is more than the surface of solids of 90 °, Super hydrophobic surface then refers to that contact angle is more than 150 ° and the roll angle solid table less than 10 ° Face, as shown in Figure 1 b, when liquid drops on hydrophobic surface, it is shaped to spherical or ellipsoid Shape.

Being different from orifice method of the prior art, nucleocapsid structure preparation method of the present utility model is skilful The core material liquid instilled in signal generating unit is entered by the hydrophobicity feature of wonderful land productivity action face 211 Row forming processes, making core material liquid molding is spheroid, can not only ensure the sphericity of stratum nucleare, And also allow for shell material liquid and more uniformly spheroid is wrapped up, thus ensure final system The nucleocapsid structure obtained has more preferable sphericity, it is seen then that direct by core relative in prior art Shell mixed solution instills in firming agent and relies on chemical reaction spontaneous in solidification process to carry out molding Mode, nucleocapsid structure preparation method of the present utility model is capable of the molding shape to nucleocapsid structure Effective control of shape, it is ensured that nucleocapsid structure has preferable sphericity.

Spheroid of the present utility model refers not only to spheroid, also includes spheroid, can also include connecing Nearly spheroid or other globoid of spheroid.Based on nucleocapsid structure preparation method of the present utility model, Can prepare and there is monolayer stratum nucleare and the nucleocapsid structure of monolayer shell, in this case, at core material In liquid titration step, core material liquid is separately formed for spherical under the effect of action face 211 Body, forms monolayer stratum nucleare；And in shell material liquid titration step, the shell material liquid core to monolayer Layer (stratum nucleare of monolayer is in type spheroid in signal generating unit in such cases) wraps Wrap up in, form monolayer shell, and ultimately form there is monolayer stratum nucleare and the nucleocapsid structure of monolayer shell. And, based on nucleocapsid structure preparation method of the present utility model, it is also possible to preparation has multilayer core The nucleocapsid structure of layer, this kind of nucleocapsid structure has at least two-layer stratum nucleare, in this case, at this In the core material liquid titration step of utility model, core material liquid is under the effect of action face 211 In type spheroid is incorporated into one-step shaping with signal generating unit is spheroid, generates list herein In unit, in type spheroid can be established at least one of which stratum nucleare；Or it is established There is the nucleocapsid conjugate of at least one of which shell.Similarly, tie based on nucleocapsid of the present utility model Body plan Preparation Method, it is also possible to preparation has the nucleocapsid structure of multilamellar shell, this kind of nucleocapsid structure has Having at least two-layer shell, in this case, in shell material liquid titration step, shell material liquid is coated with Object (namely in type spheroid in signal generating unit) can be established to have at least The nucleocapsid conjugate of one layer of shell.

In order to obtain multilamellar stratum nucleare, nucleocapsid based on nucleocapsid structure Preparation equipment of the present utility model Structure preparation method, can repeat core material liquid titration step before shell material liquid titration step The most at least twice, the spheroid with at least two-layer stratum nucleare, the most each layer core can so be formed Layer can be identical or different core material；Similarly, in order to obtain multilamellar shell, this practicality is new The nucleocapsid structure preparation method of type, can repeat shell material liquid after core material liquid titration step Body titration step at least twice, so can form the spheroid with at least two-layer shell, its In each layer shell can be identical or different shell material.

Fig. 6-8 schematically illustrates based on nucleocapsid structure Preparation equipment of the present invention and method institute energy Enough prepare has multilamellar stratum nucleare and/or the nucleocapsid structure of multilamellar shell, and wherein, Fig. 6 shows Having gone out to have monolayer stratum nucleare and the nucleocapsid structure of double-deck shell, it is followed successively by the first core from the inside to the outside Layer A1, the first shell B1 and the second shell B2；Fig. 7 shows have double-deck stratum nucleare and monolayer The nucleocapsid structure of shell, it is followed successively by the first stratum nucleare A1, the second stratum nucleare A2 and from the inside to the outside One shell B1；Fig. 8 then shows have double-deck stratum nucleare and the nucleocapsid structure of double-deck shell, its It is followed successively by the first stratum nucleare A1, the second stratum nucleare A2, the first shell B1 and the second shell from the inside to the outside Layer B2.

Additionally, be not limited to shown in Fig. 6-8, the nucleocapsid structure Preparation equipment of the present invention and method Can also prepare stratum nucleare and shell is arranged alternately has multilamellar stratum nucleare and/or multilamellar shell Nucleocapsid structure.For example, it is possible to first instill core material liquid in signal generating unit, core material liquid exists Form ground floor stratum nucleare under the effect of action face 211, then instill shell material liquid to ground floor core Layer carries out cladding and forms ground floor shell, then proceedes to instill core material liquid and is coated on ground floor shell Form second layer stratum nucleare on layer, be further continued for instilling shell material liquid and be coated on the second layer stratum nucleare formation Second layer shell, repeats according to this, thus prepare stratum nucleare and shell is arranged alternately have many Layer stratum nucleare and the nucleocapsid structure of multilamellar shell.

Visible, based on nucleocapsid structure Preparation equipment of the present utility model and nucleocapsid structure preparation side Method, can not only prepare and have monolayer stratum nucleare and the nucleocapsid structure of monolayer shell, but also permissible Preparation has multilamellar stratum nucleare and/or the nucleocapsid structure of multilamellar shell such that it is able to meet in reality Demand to all kinds of nucleocapsid structures.

Additionally, due to based on nucleocapsid structure Preparation equipment of the present utility model and method, stratum nucleare and The molding of shell is no longer dependent on the chemical reaction of self, and therefore, it is applicable not only to be prone to into The core material liquid of type, is also applied for the core material liquid of not easy-formation, thus this utility model can Effectively expand the range of choice of available core material liquid so that the preparation of the nucleocapsid structures such as biological brick is not Limited by core material liquid self-formed shaping performance again, the technical fields such as biometric print are sent out Exhibition has great importance.

In this utility model, hydrophobic surface is preferably super hydrophobic surface, does so and uses table Face 211 can improve the sphericity of the spheroid that core material liquid is formed further, and finally enters The sphericity of the nucleocapsid structure obtained by one step improvement.

In shell material liquid titration step of the present utility model, the shell material liquid cladding to spheroid Preferably carrying out in action face 211, such action face 211 also is able to play shell material liquid To certain molding effect, on the one hand shell material liquid can be made in type spherical in signal generating unit The parcel of body is more abundant and uniform, on the other hand also can improve the sphericity of formed shell, It is thus possible to improve the sphericity of the final nucleocapsid structure prepared further.

In core material liquid titration step of the present utility model, it is possible to use compressed air is by core material Liquid dispersion becomes the drop of predetermined size to instill in signal generating unit；And in shell material of the present utility model In liquid titration step, it is also possible to utilize compressed air that shell material liquid dispersion is become predetermined size Drop instills in signal generating unit.Use compressed air separatory method, due to need not to core material liquid and Shell material liquid applies vibration, less to the performance impact of core material liquid and shell material liquid, therefore can Enough effectively solution uses vibration or pulse bringing device to carry out the damage that separatory is caused in prior art The problem of evil nucleocapsid structure performance, contains the core material liquid such as collagen of cell particularly with inside, Compressed air separatory mode can significantly reduce the infringement to cytoactive, meets biometric print neck The territory bioactive requirement to nucleocapsid structure.And, by using compressed air separatory mode, Nucleocapsid structure preparation method of the present utility model can prepare the nucleocapsid structure that particle diameter is less, permissible Meet the requirement to particle diameter of the biometric print field, and the molten of absorption can be controlled accurately and real-time Liquid measure, and can more accurately control the precision of each dripping quantity, effectively reduce scale error, The coherence request to particle diameter can either be met, it is also possible to meet the diversity requirement to particle diameter.

So that shell material liquid is more easily coated on spheroid, in core material liquid titration step Before Zhou, nucleocapsid structure preparation method of the present utility model can also include pre-treatment step, should Pre-treatment step enables core material liquid or shell material liquid in type spherical with signal generating unit Body combines.In this pre-treatment step, core material liquid or shell material liquid and signal generating unit can be allowed In in type spheroid band different electric charges enable core material liquid or shell material liquid profit With electrostatic adsorption, in type spheroid is bonded to each other with signal generating unit.And in order to enter one Step improves Electrostatic Absorption effect, in this pre-treatment step, also includes core material liquid or shell material The step that the pH value of liquid is adjusted, by core material liquid or the pH value of shell material liquid It is adjusted, so that core material liquid or shell material liquid participate in the electric charge of Electrostatic Absorption more Many, the reaction of Electrostatic Absorption is the most violent, and core material liquid or shell material liquid are to whole spheroid It is coated with more abundant.Certainly, destaticing outside suction type, this pre-treatment step can also use Other modes make core material liquid or shell material liquid and in type spheroid in signal generating unit that This combines, and combination herein can be that the total material of shell material liquid or core material liquid is single with generation In unit, in type spheroid combines, it is also possible to be the part in shell material liquid or core material liquid Material spheroid in type with signal generating unit combines.

It should be noted that the dropping of shell material liquid in this utility model shell material liquid titration step Amount can be determined by precalculated mode, to realize on-demand quantitative to shell material liquid Fixed, based on this, nucleocapsid structure preparation method of the present utility model can arrange shell drop fixed Amount determines step, specifically, can enter according to parameters such as the volume of stratum nucleare, thickness and the quantities of electric charge The dripping quantity of shell material liquid is estimated and determined to row in advance, so that the shell material amount of liquid dripped is proper Good satisfied use requirement.But as a kind of alternative embodiments, in shell material of the present utility model In liquid titration step, it is also possible to first instill the shell material liquid of excess in signal generating unit, afterwards Step is removed by the residual solution in signal generating unit after shell material liquid titration step again by remaining liquid Body is discharged, and so can be prevented effectively from the parameters such as volume, thickness and the quantity of electric charge because of stratum nucleare and be difficult to Determine or determined by parameter easily exist the reasons such as deviation cause determined by shell material liquid The most inaccurate problem of dripping quantity of body, it is ensured that shell material liquid dripping quantity disclosure satisfy that use is wanted Ask.Preferably, in this remaining liquid cleaning step, in signal generating unit, first drip cleanout fluid pair Shell material liquid remaining in signal generating unit is carried out, and utilizes this cleanout fluid to remove in shell material liquid Unnecessary charge species, with avoid unnecessary charged shell material liquid vesicle surface formed non-all Even structure or bulge-structure, affect forming shape and the physicochemical property of nucleocapsid structure, then will be clear Washing liquid and remaining shell material liquid (that be not combined with spheroid, unnecessary shell material liquid) one Rise and be expelled to outside signal generating unit.

And, in order to make shell material liquid more uniformly be coated on spheroid, at this utility model Shell material liquid titration step in, can rock during shell material liquid is coated on spheroid Signal generating unit, rocks, by this, make shell material liquid be uniformly wrapped in signal generating unit spherical On body.Rocking herein can manually apply, it is also possible to applies by rocking device.Additionally, Some liquid used in nucleocapsid structure preparation have certain requirement to temperature, such as internal The core material fluid requirements temperature of the biological brick containing cell ensure that the activity of its internal cell, Therefore, in order to meet the nucleocapsid structure requirement to temperature, prepared by nucleocapsid structure of the present utility model The temperature of core material liquid and/or shell material liquid can be controlled in preparation process by method.

Nucleocapsid structure preparation method of the present utility model can also include core material liquid curing step And/or shell material liquid curing step, wherein, core material liquid curing step is arranged on core material liquid Between titration step and shell material liquid titration step, to formed in core material liquid titration step Spheroid carries out cured；Shell material liquid curing step be arranged on shell material liquid titration step it After, the shell formed in shell material liquid titration step is carried out cured, namely core material liquid Body curing schedule and shell material liquid curing step are respectively used to carry out stratum nucleare and shell at solidification Reason, owing to the liquid fluidity of the stratum nucleare after solidification and shell is weakened, the most so can make Stratum nucleare and shell are more stable, it is also possible to be further ensured that the molding effect of stratum nucleare and shell.This The cured of utility model can realize solidification by instilling firming agent in signal generating unit, I.e. firming agent curing mode, but owing to this utility model being no longer rely on the change in instillation firming agent Learning reaction and realize molding, therefore, cured of the present utility model is also no longer limited to solidification Agent curing mode, and solidification, i.e. temperature control curing mode can also be realized by controlling temperature. Visible, relative to orifice method of the prior art, nucleocapsid structure preparation method of the present utility model Available curing mode is more various and flexible.

Below in conjunction with the embodiment shown in Fig. 2-Fig. 4 prepared by nucleocapsid structure of the present utility model Equipment and nucleocapsid structure preparation method are described further, the nucleocapsid knot shown in this embodiment Structure Preparation equipment is biological brick (biological active microsphere) Preparation equipment.

As in figure 2 it is shown, in this embodiment, biological brick Preparation equipment include dropper 1, Generating means, suction nozzle storage module 3, displacement drive, device for storing liquid 6, base 7 and The bracing frame 8 being connected on base 7.

Device for storing liquid 6 is for storing core material liquid and the shell material liquid of question response and preparing Other liquid needed in journey, such as cleanout fluid.As in figure 2 it is shown, in this embodiment, storage Liquid device 6 is one and is integrated with the 61, second liquid storage space, the first liquid storage space 62 and the 3rd storage The material agents box of liquid space, wherein, stores the core material of question response in the first liquid storage space 61 Liquid, stores the shell material liquid of question response, the 3rd liquid storage space storage in the second liquid storage space 62 Deposit cleanout fluid.In order to prepare biological brick, core material liquid and shell material liquid are to be had preferably Mobility possess the liquid (such as solution and gel etc.) of biocompatibility, wherein, real at this Executing in example, in order to wrap celliferous collagen solution, (number of cells can be 1～10 to core material liquid⁶ Individual), shell material liquid is then polylysine and/or sodium alginate soln.Polylysin solution Preparation process can be: polylysine (Sigma, Mn150,000～300,000) is dissolved in PH7.2 The culture medium containing aminoacid and glucose (DMEM high glucose medium) in, obtain concentration It it is the polylysin solution of 0.05%.The preparation process of sodium alginate soln can be: by Sargassum Acid sodium is dissolved in DMEM high glucose medium, obtains the sodium alginate soln that concentration is 0.03%. It is molten that collagen solution, polylysin solution and sodium alginate soln in this embodiment is Thermo-sensitive Liquid, it is easy to accomplish temperature control solidifies, and use temperature control solidification can also avoid firming agent curing mode Infringement to cytoactive, therefore, this embodiment uses temperature control curing mode to stratum nucleare and shell Solidify, so, device for storing liquid 6 need not be provided for storing the 4th liquid storage of firming agent Space.

Dropper 1 is used for drawing liquid and being titrated to predetermined size raw by drawn liquid Become in the signal generating unit on device.As in figure 2 it is shown, in this embodiment, dropper 1 Including liquid distributing device 11 and multiple suction nozzle 12, wherein, liquid distributing device 11 include multiple for Install suction nozzle 12 suction nozzle installation portion (only illustrating in figure), multiple suction nozzle installation portions it Between distance can regulate, namely the dropper 1 in this embodiment is that multichannel spacing is adjustable Formula dropper, can complete the titration to multiple signal generating units simultaneously, and disclosure satisfy that generation Pitch requirements different between unit, titration efficiency is high, further, it is also possible to lead to by setting each The titer in road realizes preparing multiple biological brick with different-grain diameter simultaneously, it is possible to make efficiently The biological brick of standby different-grain diameter, is more beneficial for meeting the diversity requirement to biological brick in reality. In this embodiment, liquid distributing device 11 also includes that compressed air is filled with portion, and this compressed air is filled Enter portion and in the suction nozzle 12 being mounted thereon, be filled with compressed air, suction nozzle by suction nozzle installation portion Liquid in 12 is dispersed into the drop of predetermined size under compressed-air actuated effect and is dropped into In signal generating unit, owing to using compressed air separatory, therefore relative to existing vibration separatory side Formula, it is possible to significantly reduce the infringement of the activity of cell in core material liquid, meet the life of biological brick Thing characteristic requirements, particularly with the nucleocapsid structure that this particle diameter of biological brick is minimum, this advantage is more Add substantially.

As in figure 2 it is shown, in this embodiment, dropper 1 is electronic type dropper, its Including uptake test section, this uptake test section can detect and show suction nozzle 12 institute in real time The core material liquid drawn or the amount of shell material liquid, to ensure that the solution dosage drawn meets preparation Requirement, in order to avoid affecting entering smoothly of nucleocapsid structure preparation process because uptake is too little or too much OK.Visible, use the dropper 1 of this embodiment, operate easier, be advantageously implemented life Prepared by the automatization of thing brick, significantly improve preparation efficiency；Additionally, use the dropping liquid of this embodiment Device 1, it is easier to realize control to titer, and can with on-demand to core material liquid and/or Shell material liquid carries out single or multiple quantitative titration, can on-demand adjustment stratum nucleare and/or shell Quantity and thickness, such that it is able to realize the control to biological brick particle diameter, such as shown in Fig. 4, Can come by dripping different core material liquid and shell material liquid dosages in each signal generating unit Obtain stratum nucleare or the shell of different-grain diameter；And electronic type dropper is relative to existing capillary Pipe or syringe, titration precision is higher, and scale error is less such that it is able to prepare size The higher biological brick of precision, is also that the biological brick prepared and have multilamellar different-thickness shell provides Basis.

In this embodiment, the inwall of suction nozzle 12 is set to super hydrophobic surface, molten to avoid Suction nozzle 12 inwall is sticked by liquid, and, suction nozzle 12 removably connects with suction nozzle installation portion, Such as can be to use soft-touch type dismounting mode, it is simple to the replacing of suction nozzle 12 and cleaning.

Suction nozzle storage module 3 for deposit the suction nozzle 12 that disassembles from suction nozzle installation portion with And the most untapped suction nozzle 12.As in figure 2 it is shown, in this example, suction nozzle storage module 3 Being a pallet, this pallet is provided with multiple receiving hole position, and suction nozzle 12 is deposited in receiving hole position, The shape of each receiving hole position adapts with the shape of suction nozzle 12, and multiple receiving hole position in Array-like is distributed on pallet.For the ease of using, suction nozzle storage module 3 divides and has first Storage area, the second storage area and the 3rd storage area, wherein, deposit in the first storage area The suction nozzle 12 in territory is specifically designed to absorption core material liquid, deposits in the suction nozzle 12 of the second storage area Being specifically designed to absorption shell material liquid, the suction nozzle 12 depositing in the 3rd storage area is then specifically designed to Draw cleanout fluid, so can be prevented effectively from and there is the suction nozzle 12 of different purposes mutually obscure.

Generating means is for receiving the liquid dripped by dropper 1 and being core material liquid and shell The cross-linking reaction of material liquid provides reaction compartment.As it is shown on figure 3, in this embodiment, generate Device is an orifice plate 2, this orifice plate 2 be provided with multiple (can be such as 48,96 or 384) as the blind hole 21 of signal generating unit, the diapire of each blind hole 21 is each blind hole 21 Action face 211, in this embodiment, action face 211 is super hydrophobic surface, this Sample is after core material liquid and shell material liquid successively instill in this blind hole 21, and core material liquid can made With forming spheroid under the effect of the super-hydrophobicity feature on surface 211, and it is easy to shell material liquid more Add and uniformly and be fully coated in type spheroid periphery in signal generating unit, thus ensure system The standby biological brick obtained has preferable sphericity, it is achieved the control to biological brick forming shape. Owing to, for biological brick, the integrity of shell parcel can have a strong impact on the cell in stratum nucleare Survival rate, if the shell of outside wraps up insufficient or imperfect, cell is easily from shell Breach or gap overflow, so that cell is easily subject to because obtaining the effectively protection of shell To damage, survival rate reduces, and this embodiment is by arranging the action face 211 of super-hydrophobicity, Shell can uniformly and be fully coated on spheroid, and therefore, this embodiment can have Effect improves the survival rate of cell, finally improves the performance of biological brick.

In order to be shown more clearly that the effect after action face 211 is carried out super-hydrophobic process, figure When in 4, comparison shows the diapire that drop instills unprocessed and blind hole 21 after treatment Forming shape, as shown in Figure 4, the diapire of first blind hole 21 in left side is without super-hydrophobic place Reason, after liquid instills in blind hole 21, droplet profile is platypelloid type；Second, left side is risen to right Several blind holes 21 of side are all through super-hydrophobic process, after liquid instills in blind hole 21, drop shape Shape is spherical in shape.In this embodiment, the super-hydrophobicity of action face 211 can be by blind hole 21 Diapire carry out super-hydrophobic process and obtain, it is also possible to utilize super-hydrophobic material to make orifice plate 21, So various piece of each blind hole 21 and each blind hole 21 is also respectively provided with super-hydrophobicity, should Mode also is able to realize the purpose of this utility model.Wherein, by the diapire of blind hole 21 is entered The optimal way of the action face 211 that the super-hydrophobic process of row obtains super-hydrophobicity is, at clean room Interior orifice plate 21 acetone, dehydrated alcohol, deionized water etc. are embathed or clean dedusting, then By modes such as immersion or spray gun sprayings, super hydrophobic coating (is processed the painting obtained through various perfluorinates Layer or nano-sized hydrophobic layer etc. meet the material of biocompatibility) it is applied to the inwall of blind hole 21, Be placed in calorstat heating and dry.

From the figure 3, it may be seen that in this embodiment, multiple blind holes 21 are intervally installed, thus Making different signal generating units independent of one another, on the one hand this be conducive to simultaneously to multiple nucleocapsid mechanisms Be prepared, be effectively improved preparation efficiency, on the other hand can also be prevented effectively from adjacent two blind The drop in hole 21 pools big drop, it is ensured that nucleocapsid structure has less particle diameter.And, As it is shown on figure 3, these blind holes 21 are arranged in array-like, namely these blind holes 21 are along orifice plate Length L direction and the width B direction of 2 are spaced and are evenly distributed, and so arrange more just The titration to different blind holes 21 is completed in controlling dropper 1.

As shown in Figure 4, in this embodiment, the diapire of each blind hole 21 is the most U-shaped, also Action face 211 is U-shaped the most in this embodiment, utilizes the center of this U-shape structure to converge Poly-effect, so that core material liquid is easier to be shaped to spheroid, makes stratum nucleare have preferably Sphericity, and so that shell material liquid is more rapid and be coated on fully on spheroid, enter One step improves parcel effect, improves parcel efficiency.

In this embodiment, the sidewall of each blind hole 21 is provided with drainage structure and (does not shows in figure Go out), drainage structure includes outage and the closeouts blocking outage, closeouts with Outage is detachably connected, so that outage can on-demand open and close, can either ensure raw The normal preparation of thing brick, can discharge the residual liquid in blind hole 21 again easily；Meanwhile, Biological brick Preparation equipment also includes incline controller, and incline controller is arranged on orifice plate 2 Lower section, it is for discharging the remaining liq time control formed after biological brick in blind hole 21 needing Drilling plate 2 is towards the sidewall lopsidedness being provided with outage of blind hole 21 such that it is able to by blind Residual liquid in hole 21 is discharged, and the drainage structure being arranged on blind hole 21 sidewall will not shadow Ring the normal preparation of biological brick, especially do not interfere with core material liquid and (make at the diapire of blind hole 21 With surface 211) on molding effect.And, in order to prevent in the process discharging residual liquid Biological brick is discharged by middle mistake, and the pore size of outage can be set smaller than core material liquid institute The particle diameter of the spheroid formed, the spheroid that the aperture of outage is formed less than core material liquid Particle diameter, then it is necessarily less than the particle diameter of biological brick, therefore, it is possible to avoid misprinting out of biological brick. Closeouts it is not necessary to, in the case of being not provided with closeouts, higher than the liquid of outage Can discharge at any time.

As in figure 2 it is shown, in this embodiment, orifice plate 2 is immovably pacified relative to base 7 On the first base plate 71 being loaded on base 7, device for storing liquid 6 is irremovable relative to base 7 On the second base plate 72 of being installed on base 7, suction nozzle storage module 3 is relative to base 7 Immovably being installed on base 7, dropper 1 is then connected to by displacement drive On bracing frame 8, displacement drive includes XYZ motion module 43, XYZ motion module 43 are installed on bracing frame 8, and dropper 1 is connected with XYZ motion module 43, XYZ Motion module 43 is used for driving dropper 1 to move along X-axis, Y-axis and Z-direction. Visible, in this embodiment, orifice plate 2, device for storing liquid 6 and suction nozzle storage module 3 are the most motionless, Dropper 1 then can make three-dimensional motion under the driving of displacement drive, thus dropping liquid fills Put 1 and can produce X-axis, Y relative to orifice plate 2, device for storing liquid 6 and suction nozzle storage module 3 Axle and the relative motion in three directions of Z axis, and then make the dropper 1 can be real exactly Now to the absorption of solution and the titration to orifice plate 2.

As shown in Figure 2, in this embodiment, biological brick Preparation equipment also includes temperature control module. Temperature control module is for controlling core material liquid and the temperature of shell material liquid.As in figure 2 it is shown, it is real at this Executing in example, temperature control module includes the first temperature control module 51 and the second temperature control module 52, wherein, First temperature control module 51 is arranged between the first installing plate 71 and orifice plate 2, and it is used for controlling life Become the temperature of unit, on the one hand make the temperature of signal generating unit ensure that cell in core material liquid Activity, on the other hand when stratum nucleare and/or shell are solidified by needs, it is also possible to by this First temperature control module 51 controls the temperature of signal generating unit and reaches core material liquid and/or shell material liquid Solidification temperature, it is achieved temperature control solidify；Second temperature control module 52 be arranged at device for storing liquid 6 with Between second base plate 72, it is for controlling the temperature of device for storing liquid 6, so that device for storing liquid 6 Temperature can keep the activity of the cell in question response core material liquid.Visible, in this embodiment Temperature control module can either ensure that the cell in core material liquid keeps good in preparation process Activity, finally prepares and has bioactive biological brick, is capable of again temperature control solidification, Make stratum nucleare and shell more stable, and be further ensured that the molding effect of stratum nucleare and shell.

Specifically, in this embodiment, the first temperature control module 51 includes as attemperating unit Semiconductor chilling plate, temperature controller and heat abstractor, wherein, semiconductor chilling plate is used for Under the control of temperature controller, orifice plate 2 being heated or cooled, it is arranged at the end of orifice plate 2 Portion, heat abstractor is for realizing the heat transfer between semiconductor chilling plate and environment, and it is arranged on The bottom of semiconductor chilling plate, more specifically, semiconductor chilling plate has temperature control section and non-temperature control Section, temperature control end is arranged towards orifice plate 2, and non-temperature control end is arranged towards heat abstractor；And, for Ensure that heat transfer uniformly, in this embodiment, is additionally provided with between orifice plate 2 and semiconductor chilling plate Soaking plate 511, it is equal that this soaking plate 511 is capable of between semiconductor chilling plate and orifice plate 2 Even heat transfer.The structure of the second temperature control module 52 can be with the structure phase of the first temperature control module 51 Same or different, so that structure is simpler, the second temperature control module 52 of this embodiment Structure is identical with the structure of the first temperature control module 51, and here is omitted.

And, as shown in Figure 2, in this embodiment, biological brick Preparation equipment also includes controlling Device 9, this control device 9 can not only control dropping liquid by command displacement driving means and fill Put the displacement of 1, additionally it is possible to by controlling the first temperature control module 51 and the second temperature control module 52 Control the temperature needed for the temperature of orifice plate 2 and device for storing liquid 6 and core material liquid and shell material liquid Keep consistent.

Additionally, in this embodiment, biological brick Preparation equipment also includes pretreatment device (figure Not shown in) and rock device (not shown), wherein, this pretreatment device is even It is connected on device for storing liquid 6, is specifically connected to the first liquid storage space 61 and the second liquid storage space 62 On, it is used for making on core material liquid or shell material liquid band the in type spheroid phase with signal generating unit Anti-electric charge, in order to core material liquid or shell material liquid are coated in type ball in signal generating unit On shape body, namely in this embodiment, core material liquid or shell material liquid are by Electrostatic Absorption mode It is coated in signal generating unit in type spheroid；Rock device and be arranged at orifice plate 2 times Side, orifice plate 2 is applied during being coated with spheroid at core material liquid or shell material liquid by it Rock, so that core material liquid or shell material liquid more uniformly and are fully coated on spheroid, Thus prepare more complete and uniform biological brick, improve the physicochemical property of biological brick further.

Biological brick Preparation equipment based on this embodiment, preparation has monolayer stratum nucleare and monolayer shell The biological brick preparation method of nucleocapsid structure as follows:

Pre-treatment step: utilize pretreatment device to the core material in the first liquid storage space 61 Opposite charges on shell material liquid band in liquid and the second liquid storage space 62；

Core material liquid titration step: utilize dropper 1 to draw in the first liquid storage space 61 Core material liquid, and utilize dropper 1 that the core material liquid dispersion drawn is become predetermined size Drop instills in the blind hole 21 on orifice plate 2, makes the core material liquid in instillation blind hole 21 in blind hole The effect compacted under of the diapire (action face 211) of 21 is spheroid, forms stratum nucleare；

Core material liquid curing step: control the temperature of orifice plate 2 extremely by the first temperature control module 51 The temperature of blind hole 21 reaches the solidification temperature of core material liquid, it is achieved to core material liquid titration step Formed in the cured of spheroid；

Shell material liquid titration step: utilize dropper 1 to draw in the second liquid storage space 62 Shell material liquid, and utilize dropper 1 that the shell material liquid dispersion drawn is become predetermined size Drop instills in the blind hole 21 on orifice plate 2 so that the shell material liquid instilled in blind hole 21 is being made Under effect with surface 211, stratum nucleare is coated with, and by rocking dress during this cladding Put and rock orifice plate 21 and shell material liquid is coated on stratum nucleare equably and crosslinks with stratum nucleare Reaction, forms shell；

Shell material liquid curing step: control the temperature of orifice plate 2 extremely by the first temperature control module 51 The temperature of blind hole 21 reaches the solidification temperature of shell material liquid, it is achieved to shell material liquid titration step Formed in the cured of shell；

Remaining liquid removes step: utilize dropper 1 to draw the cleanout fluid in the 3rd liquid storage space also Cleanout fluid is instilled in the blind hole 21 with remaining shell material liquid, to the remaining shell in blind hole 21 Material liquid is carried out, and together with remaining shell material liquid, cleanout fluid is expelled to blind hole 21 Outside.

Find through research, in order to obtain more preferable Electrostatic Absorption effect, walk in above-mentioned pretreatment In Zhou, it is also possible to the pH value of core material liquid is adjusted, such as can be by core material liquid PH value regulates to 6-10 (being preferably adjusted to 7.6), under the conditions of this pH value, comprises thin The quantity of electric charge participating in electrostatical binding in the collagen solution of born of the same parents is more, and the reaction of electrostatical binding is more Acutely, such that it is able to obtain more preferable Electrostatic Absorption effect；And, walk at core material liquid curing In rapid and shell material liquid curing step, the temperature of cured may be controlled to 20-40 ° (excellent Selected control is made as 37 °), can be set as that (hardening time is permissible hardening time 5-180 minute Need to select within the range according to material, be preferably set to 30 minutes), at this solidification Under the conditions of reason, it is possible to the stratum nucleare after preferably being solidified and shell, and in ensure that stratum nucleare Cell there is preferable biological activity.

Based on above steps, can prepare and there is monolayer stratum nucleare and the biological brick of monolayer shell, And in order to obtain multilamellar stratum nucleare, only core material need to be repeated in before shell material liquid titration step Each step before liquid curing step at least twice, so can form at least two-layer stratum nucleare, " before shell material liquid titration step " herein refers to not yet implement shell material liquid titration step Time, and " each step before core material liquid curing step " refers to core material liquid curing step Rapid in interior each step；And in order to obtain multilamellar shell, also only need to be in shell material liquid curing step Afterwards, shell material liquid titration step it is repeated in each step between shell material liquid curing step At least twice, so can form at least two-layer shell, " walking herein at shell material liquid curing After Zhou " refer to have been carried out shell material liquid curing step after, and " shell material liquid titration step Suddenly to each step of shell material liquid curing step " refer to shell material liquid titration step and shell material Liquid curing step is in interior each step.Visible, biological brick preparation method based on this embodiment, Can not only prepare and there is monolayer stratum nucleare and the biological brick of monolayer shell, but also tool can be prepared There are multilamellar stratum nucleare and/or the biological brick of multilamellar shell such that it is able to meet in reality each nucleoid The demand of shell structure.Such as, can prepare based on this biological brick preparation method and include one layer of stratum nucleare With the biological brick structure of three layers of shell, one layer of stratum nucleare is for wrapping celliferous collagen solution, three layers of shell Layer is respectively coated on stratum nucleare periphery and the polylysine layer being arranged in order from inside to outside, alginic acid Sodium layer and polylysine layer, wherein, the electric charge that collagen solution is carried and polylysine layer are carried Opposite charge, the opposite charge that sodium alginate layer and polylysine layer are carried, with ensure each layer it Between mutual absorption.

Additionally, temperature control module can be utilized in These steps to described core material liquid and described Shell material liquid carries out temperature control, specifically, in above-mentioned pre-treatment step, it is possible to use the Two temperature control modules 52 control the core material liquid in device for storing liquid 6 and the temperature of shell material liquid, with Ensure that core material liquid and the shell material liquid of question response can keep preferable biological activity；And at core In material liquid titration step and shell material liquid titration step, it is possible to use the second temperature control module 52 Core material liquid in blind hole 21 and shell material liquid are carried out temperature control, so that in blind hole 21 Core material liquid and shell material liquid can keep preferable biological activity.

In order to be shown more clearly that the using method of this embodiment biological brick Preparation equipment, below tie Close each step stating in biological brick preparation method by the biological brick Preparation equipment of this embodiment Operating procedure is described as follows.

When implementing the core material liquid assimilating step in core material liquid titration step, this embodiment is raw The operating procedure of thing brick Preparation equipment is: first sets the solution uptake of dropper 1, drip The parameters such as dosage and separatory speed；Then liquid distributing device 11 is driven by XYZ motion module 43 Mobile above the first storage area of suction nozzle storage module 3, the first storage area will be deposited in Suction nozzle 12 be installed on the suction nozzle installation portion of liquid distributing device 11；Move dropper 1 again Above the first liquid storage space 61 in liquid storage space 6, and driven by XYZ motion module 43 Suction nozzle 12 moves downwardly to along Z axis in stretching into the first liquid storage space 61 and draws core material liquid, Complete the absorption to core material liquid.Wherein, at suction nozzle 12, core material liquid is carried out actual absorption Before sampling, it is also possible to beforehand through twice imbibition and discharge opeing, suction nozzle 12 is carried out rinse, and When core material liquid is formally drawn sampling, can make suction nozzle 12 and vertical direction in 20 ° of at an angles stretch in the first liquid storage space 61, and can be with Real Time Observation dropper 1 institute The absorption information of the core material liquid of display, after absorption information reaches predetermined solution uptake, will Suction nozzle 12 removes from the first liquid storage space 61.

When core material liquid in implementing core material liquid titration step instills step, this embodiment is raw The operating procedure of thing brick Preparation equipment is: that is moved by dropper 1 to orifice plate 21 is to be titrated The top of blind hole 21 so that suction nozzle 12 is directed at blind hole 21, and is set by dropper 1 It is set to separatory pattern, then by pouring compressed air in suction nozzle 12 by the core in suction nozzle 12 Material liquid dispersion becomes the drop of predetermined size to instill in different blind holes 21, completes core material liquid The instillation of body.

When implementing the shell material liquid assimilating step in shell material liquid titration step, this embodiment is raw The operating procedure of thing brick Preparation equipment is: first move apart above orifice plate 21 by dropper 1, Carry out blowing liquid, by core material liquid emptying remaining in suction nozzle 12；Then reset solution to inhale Taken amount, infusion volume and separatory speed, move to suction nozzle storage module 3 by dropper 1 Above one storage area, in pulling down suction nozzle 12 and being positioned over the receiving hole position of the first storage area； Liquid distributing device 11 is moved above the second storage area of suction nozzle storage module 3 again, will deposit The suction nozzle 12 being put in the second storage area is installed on suction nozzle installation portion；Finally by dropper 1 moves above the second liquid storage space 62 in liquid storage space 6, and falls suction nozzle 12 to stretching into Draw shell material liquid in second liquid storage space 62, complete the absorption to shell material liquid.

When shell material liquid in implementing shell material liquid titration step instills step, this embodiment is raw The operating procedure of thing brick Preparation equipment is: dropper 1 moves the core material liquid to orifice plate 21 The top of the blind hole 21 titrated in body titration step so that suction nozzle 12 is directed at blind hole 21, And dropper 1 is set to separatory pattern, then by pouring compression sky in suction nozzle 12 Shell material liquid dispersion in suction nozzle 12 is become the drop of predetermined size to instill different blind holes 21 by gas In, complete the instillation to shell material liquid.

When implementing remaining liquid and removing step, the operating procedure of this embodiment biological brick Preparation equipment For: dropper 1 is moved apart above orifice plate 21, carry out blowing liquid, by remnants in suction nozzle 12 Shell material liquid emptying；Dropper 1 is moved the second storage area to suction nozzle storage module 3 Top, in pulling down suction nozzle 12 and being positioned over the receiving hole position of the second storage area；Again by separatory Device 11 moves above the 3rd storage area of suction nozzle storage module 3, will deposit in the 3rd The suction nozzle 12 of storage area is installed on suction nozzle installation portion；Afterwards dropper 1 is moved to The 3rd liquid storage space above in liquid storage space 6, and it is empty to stretching into the 3rd liquid storage to fall suction nozzle 12 Interior absorption cleanout fluid, completes the absorption to cleanout fluid；Subsequently dropper 1 is moved to The top of the blind hole 21 titrated in shell material liquid titration step so that suction nozzle 12 and blind hole 21 alignments, and dropper 1 is set to separatory pattern, by pouring pressure in suction nozzle 12 Shell material liquid dispersion in suction nozzle 12 is become the drop of predetermined size to instill each blind hole 21 by contracting air In, complete the instillation to cleanout fluid；Incline controller is finally utilized to make orifice plate 2 towards being provided with The sidewall lopsidedness of drainage structure, and open the closeouts on outage so that cleanout fluid with Remaining shell material liquid is outside outage is expelled to blind hole 21.

It should be noted that owing to core material liquid curing step and shell material liquid curing step are both needed to Wanting certain response time, therefore, above-mentioned enforcement shell material liquid titration step and the remaining liquid of enforcement are clear Carry out except operating procedure during step can make full use of these response time, and need not account for again With the extra time, so, use the biological brick preparation method of this embodiment significantly to save About preparation time, improves preparation efficiency.

Visible, the nucleocapsid structure Preparation equipment of this embodiment has the advantages that

(1) the super-hydrophobicity feature utilizing action face 211 makes core material liquid molding be spherical Body, and enable shell material liquid more uniformly and to be fully coated on stratum nucleare, it is possible to it is right to realize The control of biological brick forming shape, can be effectively improved the sphericity of biological brick；

(2) action face 211 is arranged on orifice plate 2 in blind hole 21, puts down compared to simple The super-hydrophobic plate of face configuration, not only preparation efficiency can significantly improve, and by orifice plate 2 The hole wall of upper each blind hole 21 the biological brick preparation process in adjacent two blind holes 21 is carried out every From, it is possible to ensure the independence of each biological brick preparation process, and be easy to the preparation at biological brick Cheng Zhong, makes its shell material liquid more fully and equably wrap up by rocking orifice plate 2, enters one Step promotes integrity and the uniformity of shell material liquid parcel, is conducive to improving biological brick further Physicochemical property；

(3) dropper 1 uses compressed air separatory mode, can effectively reduce biology The damage of the cytoactive in brick stratum nucleare, it is ensured that obtained biological brick disclosure satisfy that biometric print The field requirement to its biological nature；

(4) by electronic type dropper, core material liquid and shell material liquid are the most accurately dripped In action face 211, it is possible to prepare that particle diameter is less, the higher biology of dimensional accuracy Brick, and be conducive to controlling stratum nucleare and the respective thickness of shell, it is possible to realize stratum nucleare and shell size On-demand independent control and adjustment, the most reproducible, and can realize differentiation adjust；

(5) by the way of temperature control, realize the solidified forming of stratum nucleare and shell, be more beneficial for protecting Hold the biological activity of the internal cell of biological brick；

(6) technology is controlled by automated machine, it is possible to quickly prepare biological brick, during preparation Between short, preparation efficiency is high, prepared by the batch being advantageously implemented biological brick.

As a kind of modification of aforementioned first embodiment, this utility model additionally provides nucleocapsid structure The difference of the second embodiment of Preparation equipment, this second embodiment and aforementioned first embodiment Be following some: (1) displacement drive also includes XY motion module, and this XY transports Dynamic model group is arranged on the lower section of orifice plate 2 and for driving orifice plate 2 to make two maintenance and operations in X/Y plane Dynamic, so when carrying out core material liquid and the titration of shell material liquid, except XYZ can be utilized to transport Dropper 1 is moved above orifice plate 2 by dynamic model group 43, it is also possible to utilize this XY to move Module adjusts the position of orifice plate 2, the position of orifice plate 2 is finely adjusted calibration, it is achieved suction nozzle 12 are directed at location more accurately with blind hole 21, and the kinematic accuracy of this XY motion module can be 0.02mm, so can meet the preparation requirement of biological brick, and the increase being unlikely to again too much sets Meter and processing cost；(2) temperature control module no longer includes the second temperature control module 52；(3) as Shown in Fig. 5, the diapire of blind hole 21 is plane, namely action face 211 is plane；(4) Drainage structure (not shown) is located on the diapire of blind hole 21, and nucleocapsid structure preparation sets For no longer including incline controller.Other structures of this embodiment and aforementioned first embodiment base This is identical, is specifically referred to the explanation of aforementioned first embodiment, and here is omitted.

The foregoing is only exemplary embodiment of the present utility model, not new in order to limit this practicality Type, all within spirit of the present utility model and principle, any amendment of being made, equivalent, Improve, within should be included in protection domain of the present utility model.

Claims

1. a nucleocapsid structure Preparation equipment, it is characterised in that include dropper (1) and Generating means, described generating means includes that at least one signal generating unit, described signal generating unit have Action face (211), described action face (211) is hydrophobic surface, and described dropping liquid fills Put (1) to be used for instilling in described signal generating unit by core material liquid and/or shell material liquid, described work Make described core material liquid separately formed for spheroid or make described core material liquid with surface (211) Being incorporated into one-step shaping with spheroid in type in described signal generating unit is spheroid, described shell Material liquid is coated in described signal generating unit and forms shell in type spheroid and in described life Become in unit and form spheroid further.

Nucleocapsid structure Preparation equipment the most according to claim 1, it is characterised in that institute Stating action face (211) is plane, or, described action face (211) includes lower concave curved Face.

Nucleocapsid structure Preparation equipment the most according to claim 2, it is characterised in that institute Stating signal generating unit is flat board, and described action face (211) is the plate face of described flat board；Or, Described signal generating unit is the chamber of top end opening, and the diapire of described chamber is plane or includes institute Stating lower concave curved surface, described action face (211) is the diapire of described chamber.

Nucleocapsid structure Preparation equipment the most according to claim 2, it is characterised in that institute State that lower concave curved surface is U-shaped or ball crown type.

Nucleocapsid structure Preparation equipment the most according to claim 1, it is characterised in that institute Stating generating means and include signal generating unit described at least two, described at least two, signal generating unit is each other It is arranged at isolator in described generating means.

Nucleocapsid structure Preparation equipment the most according to claim 1, it is characterised in that institute State nucleocapsid structure Preparation equipment also to include rocking device, described in rock device at described core material Liquid or described shell material liquid are coated with in described signal generating unit and make during in type spheroid It is described that the generation of described signal generating unit can make described core material liquid or described shell material liquid be uniformly wrapped on Rocking in type spheroid in signal generating unit.

Nucleocapsid structure Preparation equipment the most according to claim 1, it is characterised in that institute State generating means and also include that drainage structure, described drainage structure are used for discharging formation described nucleocapsid knot Remaining liq in described signal generating unit after structure.

Nucleocapsid structure Preparation equipment the most according to claim 7, it is characterised in that institute Stating the chamber that signal generating unit is top end opening, the diapire of described chamber is described action face (211), wherein, described drainage structure is arranged on the diapire of described chamber；Or, described Drainage structure is arranged on the sidewall of described chamber.

Nucleocapsid structure Preparation equipment the most according to claim 8, it is characterised in that institute Stating drainage structure to be arranged on the sidewall of described chamber, described nucleocapsid structure Preparation equipment also includes Incline controller, described incline controller is for institute after discharging the described nucleocapsid structure of formation Control described signal generating unit when stating the remaining liq in signal generating unit and be provided with institute towards described chamber State the sidewall lopsidedness of drainage structure.

Nucleocapsid structure Preparation equipment the most according to claim 7, it is characterised in that institute State the outage that drainage structure includes connecting with described signal generating unit.

11. nucleocapsid structure Preparation equipments according to claim 10, it is characterised in that institute State the closeouts that drainage structure also includes blocking described outage, described closeouts and institute State outage detachably connected.

12. nucleocapsid structure Preparation equipments according to claim 1, it is characterised in that institute State dropper (1) and include liquid distributing device (11) and at least one suction nozzle (12), described suction Head (12) can draw described core material liquid and/or described shell material liquid, described liquid distributing device (11) It is filled with portion including compressed air and at least one is installed for the suction nozzle installing described suction nozzle (12) Portion, the described compressed air portion of being filled with is filled in described suction nozzle (12) by described suction nozzle installation portion Enter compressed air the described core material liquid in described suction nozzle (12) or described shell material liquid to be divided The drop dissipating into predetermined size instills in described signal generating unit.

13. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State the inwall of suction nozzle (12) at least for dripping described core material liquid and/or described shell material liquid The part of dropping end is hydrophobic surface.

14. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State dropper (1) and also include that uptake test section, described uptake test section are used for detecting institute State described core material liquid or the uptake of described shell material liquid that suction nozzle (12) is drawn.

15. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State core material liquid and/or the uptake scalable of described shell material liquid.

16. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State dropper (1) and include suction nozzle described at least two (12), suction nozzle (12) described at least two In at least one be used for drawing described core material liquid, in suction nozzle (12) described at least two extremely Rare one is used for drawing described shell material liquid.

17. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State liquid distributing device (11) and include suction nozzle installation portion described at least two, suction nozzle described at least two Distance between installation portion can regulate.

18. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State suction nozzle (12) to be removably installed on described suction nozzle installation portion.

19. nucleocapsid structure Preparation equipments according to claim 12, it is characterised in that institute State nucleocapsid structure Preparation equipment and also include suction nozzle storage module (3), described suction nozzle storage module (3) For depositing described suction nozzle (12).

20. nucleocapsid structure Preparation equipments according to claim 1, it is characterised in that institute State nucleocapsid structure Preparation equipment and also include that displacement drive, described displacement drive are used for controlling Make the relative motion of described dropper (1) and described signal generating unit.

21. nucleocapsid structure Preparation equipments according to claim 1, it is characterised in that institute Stating nucleocapsid structure Preparation equipment and also include device for storing liquid (6), described device for storing liquid (6) is at least Including the first liquid storage space (61) and the second liquid storage space (62), described first liquid storage space (61) being used for storing described core material liquid, described second liquid storage space (62) is used for storing institute State shell material liquid.

22. nucleocapsid structure Preparation equipments according to claim 21, it is characterised in that institute State device for storing liquid (6) and also include that the 3rd liquid storage space, described 3rd liquid storage space are used for storing clearly Washing liquid；And/or, described device for storing liquid (6) also includes the 4th liquid storage space, described 4th storage Liquid space is used for storing firming agent.

23. nucleocapsid structure Preparation equipments according to claim 1, it is characterised in that institute State nucleocapsid structure Preparation equipment and also include that temperature control module, described temperature control module are used for controlling described core Material liquid and/or the temperature of described shell material liquid.

24. nucleocapsid structure Preparation equipments according to claim 23, it is characterised in that institute State temperature control module and include that the first temperature control module (51), described first temperature control module (51) are used for Control the temperature of described signal generating unit so that the temperature of described signal generating unit can be with described core material liquid Temperature required for body and/or described shell material liquid keeps consistent；And/or, described nucleocapsid structure Preparation equipment also includes that device for storing liquid (6), described device for storing liquid (6) at least include the first storage Liquid space (61) and the second liquid storage space (62), described first liquid storage space (61) is used for Storing described core material liquid, described second liquid storage space (62) is used for storing described shell material liquid, Described temperature control module includes the second temperature control module (52), and described second temperature control module (52) is used In controlling the temperature of described device for storing liquid (6) so that the temperature of described device for storing liquid (6) can Keep consistent with the temperature required for described core material liquid and/or described shell material liquid.

25. nucleocapsid structure Preparation equipments according to claim 1, it is characterised in that institute Stating nucleocapsid structure Preparation equipment and also include pretreatment device, described pretreatment device is used In carrying out making described core material liquid or described to described core material liquid and/or described shell material liquid The pretreatment that in type spheroid is combined in described signal generating unit of shell material liquid.

26. nucleocapsid structure Preparation equipments according to claim 25, it is characterised in that institute State pretreatment device by making described core material liquid and/or described shell material liquid and described life Opposite charges in type spheroid band in one-tenth unit.

27. according to the arbitrary described nucleocapsid structure Preparation equipment of claim 1-26, and its feature exists In, described nucleocapsid structure Preparation equipment is biological active microsphere Preparation equipment.

28. according to the arbitrary described nucleocapsid structure Preparation equipment of claim 1-26, and its feature exists In, described hydrophobic surface is super hydrophobic surface.