A kind of double emulsion containing solid core prepares micro fluidic device and preparation method
Technical field
The invention belongs to prepare double emulsion technical field, particularly relate to a kind of current containing the solid dual breast of core for solving
In liquid technology of preparing, and the coaxial diffusion that has that mesophase is poor to solid core parcel property, the solid caducous problem of core designs declines
Passage and the micro fluidic device of focusing emulsifying architectural feature.
Background technology
Double emulsion is the three-phase system of a kind of nested structure, different according to each phase material, can be divided into liquid-liquid-liquid three
Phase double emulsion or one-tenth solid-liquid-liquid three-phase double emulsion.Double emulsion has the nucleocapsid structure of uniqueness, and carrying out, medicine is defeated
The fields such as fortune, food delivery, Chemical Decomposition, microreactor and microstructure unit have the highest using value.Currently, for
The double emulsion preparation of Liquid-Liquid-Liquid Systems has had a perfect method, but dual for solid-liquid-liquid tri-phase system
What emulsion technology of preparing was developed also compares shortcoming.
The double emulsion technology of preparing containing solid core commonly used contains very imperfection, generally two kinds of methods of use:
(1) continuous mixing and emulsifying method.By being added in the first liquid phase by solid core, once stirring, entirety is led the most again
Enter in second liquid phase, carry out secondary stirring, thus prepare double emulsion.But the double emulsion polydispersity that this method produces
Greatly, emulsion controllability is very poor.
(2) micro-fluidic emulsion process.Utilize fluid shear action in microfluidic channel, it is achieved Gu core parcel, this side
The emulsion monodispersity that method produces is high.But the double emulsion that currently employed T-shaped microchannel generates, Gu core cladding difficulty is big,
And be coated with successful double emulsion solid core of also going on a journey once in a while and come off.
To this end, solid core can not only be wrapped up in the urgent need to exploitation, and prepare stable containing solid core double emulsion and
Gu the method for core difficult drop-off.
Being inspired by microflow control technique, the present invention utilizes capillary tube construction from part, builds emulsifying microchannel, and passes through structure
Design, it is achieved parcel efficient to solid core, stable.Produced double emulsion all has at the aspect such as structure control and form stable
Outstanding performance.
Summary of the invention
The technical problem to be solved is for above-mentioned the deficiencies in the prior art, and provides one and prepare containing solid
Have capillary tube package assembly micro-fluidic chip, ten triple channel coaxial construction and the flow focusing formula emulsion of the double emulsion of core are cut
Cut the micro fluidic device of district's feature.This device can be prepared effectively containing solid core double emulsion, and controls double emulsion structure
Feature.
Technical scheme
For solving the above-mentioned technical problem that conventional solid ball technique for packing exists, the technical solution used in the present invention is:
A kind of double emulsion containing solid core prepares micro fluidic device, including internal phase capillary tube, mesophase capillary tube and outer
Phase capillary tube, it is characterised in that: described mesophase capillary tube includes a big capillary tube of central circular and is looped around described middle part circle
The multiple coaxial little capillary tube of circle uniform outside the big capillary tube of shape, the described little capillary tube of coaxial circle collectively forms centre
Phase microchannel;Described internal phase capillary tube inserts the big capillary tube of described central circular, constitutes internal phase microchannel;At described mesophase hair
Being provided with one between tubule with foreign minister's capillary tube and be connected capillary tube, described mesophase capillary tube and foreign minister's capillary tube are from described connection
The both sides of capillary tube are inserted and spaced apart composition emulsion band, a length of n of described emulsion band, 0.5 (a2+b2)≤n≤1.5(a2+
b2), a2For the external diameter of the big capillary tube of central circular, b2For the external diameter of circular little capillary tube, the end of the foreign minister's capillary tube in emulsion band
Portion is taper, and tapering is q, and 30 °≤q≤60 °, is formed with outlet at described foreign minister's capillary tube with described connection between capillary tube
It is positioned at the foreign minister microchannel of described emulsion band, described internal phase capillary tube outside diameter dinnerCapillary inner diameter big with described central circular
DmiddleRelation be: dinner=Dmiddle-h, wherein, h=50-100 μm, described central circular big capillary inner diameter Dmiddle, with
Described foreign minister capillary inner diameter douterRelation be: Dmiddle=douter-l, wherein, l=100-300 μm.
The external diameter a of the big capillary tube of central circular2The external diameter b of capillary tube little with circle2Relation be: a2/b2=(1-
Sin15 °)/sin15 °, the external diameter a of the big capillary tube of central circular1The external diameter a of capillary tube big with central circular2Relation be: a1=
a2-m, the internal diameter b of circular little capillary tube1The external diameter b of capillary tube little with circle2Relation be: b1=b2-m, wherein, 50 μm≤m≤
150μm。
Described connection capillary tube is square tube, the external diameter a of the big capillary tube of central circular2, the external diameter b of circular little capillary tube2, outer
Phase capillary tube outer diameter D2And the relation between length of side l of the square endoporus of square tube is: a2+b2=l-k, D2=l-k, wherein,
K=5-20 μm.
Described internal phase capillary tube, mesophase capillary tube, foreign minister's capillary tube and connection capillary tube are overall by dispensing needle head
It is fixed on after connection on a microscope slide.
Input at described internal phase capillary tube connects an internal phase syringe pump, and the entrance at the little capillary tube of described circle connects
Connecing a mesophase syringe pump, the entrance in described foreign minister microchannel connects has foreign minister's syringe pump, at described foreign minister's capillary tube
Outlet connection has a double emulsion to collect container.
Described internal phase capillary tube, mesophase capillary tube, foreign minister's capillary tube and connection capillary tube are capillary glass tube.
A kind of method using any of the above-described capillary tube micro fluidic device to prepare microsphere, it is characterised in that: will include
The internal phase liquid of solid ball injects internal phase capillary tube by internal phase syringe pump, is injected in the middle of this injection by mesophase by mesophase liquid
Phase microchannel, injects foreign minister microchannel by foreign minister's liquid by foreign minister's syringe pump, and regulates each foreign minister's liquid, mesophase liquid and internal phase liquid
Flow, it is achieved solid ball list parcel and wrap up more.
A kind of double emulsion containing solid core of the present invention prepares micro fluidic device, and it is micro-that capillary tube uses simple assembling mode to constitute
Passage;Coaxial circular capillaries utilizes main channel to transport solid core, is passed through mesophase fluid and realizes solid from 360 ° in passage
Core wraps up;Coaxial circular capillaries and foreign minister's circular capillaries size promote coaxial with square capillary tube coupling, and collaborative square
Capillary tube constitutes flow focusing emulsion shear zone.
(internal diameter and external diameter are respectively c for coaxial circular capillaries and foreign minister's circular capillaries1, c2) from square capillary tube (interior rib
A length of both sides l) are inserted, and spacing distance is n, wherein 0.5 (a2+b2)≤n≤1.5(a2+b2), constituted emulsion with this and sheared
District, mainly utilizes flow focusing behavior to realize fluid shearing effect in this shear zone.
Micro-fluidic chip uses capillary tube to assemble, and simple in construction easily realizes, significantly reduces micro-fluidic chip manufacture
Difficulty.And the emulsion preparation containing solid core be by fluid between shear action realize, drastically increase prepared breast
The monodispersity of liquid, meanwhile, the internal structure (Gu nuclear volume, double emulsion wall thickness) of double emulsion is controlled.Capillary tube all uses
Glass micro-fluidic device, by capillary tube is carried out surface modification, can apply to solid-water-oil and solid-oil-water double emulsion
System.
Beneficial effect:
The invention discloses a kind of double emulsion containing solid core and prepare micro fluidic device, use construction from part to build micro-fluidic dress
Put, simple and convenient, it is beneficial to high-volume, industrialized production.In constructed micro fluidic device, mesophase co-axial capillaries, it is achieved
The mesophase fluid 360 ° of parcels to solid core, the prepared double emulsion parcel property containing solid core is good, is difficult to the problem of coming off occur.
And this device can also wrap up by the regulation of each phase flow rate is realized multinuclear, for providing wider containing the preparation of solid core double emulsion
General use space.
Accompanying drawing explanation
A kind of double emulsion containing solid core of Fig. 1 prepares micro fluidic device schematic diagram.
Fig. 2 micro-fluidic chip schematic diagram.
Fig. 3 ten triple channel coaxial circular capillaries schematic diagram.
Fig. 4 capillary tube package assembly schematic diagram.
Fig. 5 is the connection side view of foreign minister's capillary tube and mesophase capillary tube.
Fig. 6 prepares embodiment 1 schematic diagram containing single solid core double emulsion.
Fig. 7 prepares embodiment 2 schematic diagram containing two solid core double emulsions.
Fig. 8 prepares embodiment 3 schematic diagram containing three solid core double emulsions.
Fig. 9 prepares embodiment 4 schematic diagram containing four solid core double emulsions.
1. internal phase syringe pump in figure;2. mesophase syringe pump;3. foreign minister's syringe pump;4. micro-fluidic chip;5. double emulsion
Collect container;6. dispensing needle head;7. microscope slide;8. solid ball transports circular capillaries;9. the ten coaxial circular capillaries of triple channel;
The most square capillary tube;11. foreign minister's circular capillaries;12. solid core, internal phase fluid-mixings;13. mesophase fluids;14. solid cores;
15. external fluid phases.
Detailed description of the invention:
Below in conjunction with the accompanying drawings the preferred embodiments of the present invention is further described in detail, so that advantages of the present invention
Can be easier to be readily appreciated by one skilled in the art with feature:
Fig. 1 gives a kind of capillary tube micro fluidic device schematic diagram for solid core parcel, in concrete structure includes
Phase syringe pump 1;Mesophase syringe pump 2;Foreign minister's syringe pump 3;Micro-fluidic chip 4;Double emulsion collects container 5.Internal phase syringe pump 1
Transporting inlet microchannel with the solid ball of micro-fluidic chip 4 to be connected, mesophase syringe pump 2 is micro-with the mesophase of micro-fluidic chip 4
Channel entrance is connected, and foreign minister's syringe pump is connected with the foreign minister microchannel of micro-fluidic chip 4, and double emulsion catcher 5 is with micro-fluidic
The outlet microchannel of chip 4 is connected.
Fig. 2 gives micro-fluidic chip schematic diagram, and concrete structure includes dispensing needle head 6;Microscope slide 7;Solid ball transports circle
Shape capillary tube 8;The ten coaxial circular capillaries of triple channel 9;Square capillary tube 10;Foreign minister's circular capillaries 11.Ten triple channel are coaxial
Circular capillaries 9 and foreign minister's circular capillaries 11 are inserted from square capillary tube 10 both sides.Solid ball is transported circular capillaries 8 from
Insert certain depth at the big channel entrance in middle part of the ten coaxial circular capillaries of triple channel 9, and seal seam with epoxide-resin glue
Place, is careful not to block cincture passage, constitutes solid ball and transports microchannel.Then with epoxide-resin glue, this capillary tube is assembled
Structure is integrally fastened to slide surface, and then dispensing needle head 6 carves groove, and with epoxide-resin glue by dispensing needle head 6 points
Be not bonded at the ten coaxial circular capillaries of triple channel 9 at the passage, square capillary tube 10 circle coaxial with ten triple channel capillary
Joint between pipe 9 and foreign minister's circular capillaries 9 and square intercapillary joint, constitute integrally closed structure.
The wherein composition mesophase microchannel at passage of the ten coaxial circular capillaries of triple channel 9, outside foreign minister's circular capillaries 9 is constituted
Phase microchannel.
Fig. 3 gives the schematic diagram of the ten coaxial circular capillaries of triple channel, as it can be seen, the coaxial circular capillary of ten triple channel
By 1 big capillary tube of central circular, (internal diameter and external diameter are respectively a to pipe 91, a2) the circular little capillary tube of the circulating type identical with 12
(internal diameter and external diameter are respectively b1, b2) tangent composition, wherein a2/b2=(1-sin15 °)/sin15 °, a1=a2-m, b1=b2-m,
50μm≤m≤150μm。
Fig. 4, Fig. 5 give capillary tube package assembly schematic diagram, and concrete structure includes that solid ball transports circular capillaries 8;
The ten coaxial circular capillaries of triple channel 9;Square capillary tube 10;Foreign minister's circular capillaries 11.The ten coaxial circular capillaries of triple channel 9
(internal diameter and external diameter are respectively c with foreign minister's circular capillaries 111, c2) insert from the both sides of square capillary tube 10 (a length of l of interior rib),
And spacing distance is n, wherein 0.5 (a2+b2)≤n≤1.5(a2+b2), constituted emulsion shear zone with this, main in this shear zone
Flow focusing behavior is utilized to realize fluid shearing effect.In emulsion shear zone, foreign minister's circular capillaries 11 is taper, and tapering is q,
And 30 °≤q≤60 °.The external diameter of the ten coaxial circular capillaries of triple channel 9 and foreign minister's circular capillaries 11 and square capillary tube 10
Interior rib length is mated, to realize fixing internal nesting capillary tube and to promote coaxial effect, i.e. a2+b2=l-k, D2=l-k, wherein, k
=5-20 μm.
Fig. 6-Fig. 9 gives 4 embodiment schematic diagrams of solid core parcel, below in conjunction with the accompanying drawings, is specifically described.
The embodiment that a kind of double emulsion containing solid core prepares micro fluidic device is embodied as step:
(1) preparation related solution, for solid-water-oil systems, solid ball can be selected for PLGA solid ball, internal phase, mesophase water
Solution can be selected for 2%PVA aqueous solution, and foreign minister's oil solution can be selected for the dimethicone that viscosity is 100CS.For solid-oil-water
System, solid ball can be selected for PLGA solid ball, and internal phase, mesophase oil solution can be selected for ethoxylated trimethylolpropane three acrylic acid
Ester (ETPTA), foreign minister's aqueous solution can be selected for the PVA aqueous solution of 2%;
(2) for solid-water-oil systems, square capillary tube 10 and foreign minister's circular capillaries 11 are carried out hydrophobic treatment;For
Gu-oil-water system, square capillary tube 10 and foreign minister's circle capillary 11 are carried out hydrophilic treated;
(3) the ten coaxial circular capillaries of triple channel 9 and foreign minister's circular capillaries 11 are inserted from square capillary tube 10 both sides,
And solid ball is transported circular capillaries 8 insert certain depth from ten triple channel coaxial circular capillaries 9 import departments, use asphalt mixtures modified by epoxy resin
Fat glue seals seam crossing.Then with epoxide-resin glue, this structure is integrally fastened to slide surface, then by dispensing needle head 6 quarter
Go out groove, be fixed on capillary tube joint with epoxide-resin glue, constitute integral seal structure, build capillary tube microfluidic chip,
Finishing device is built;
(4) the solution correspondence internal phase of solid ball and preparation, mesophase, foreign minister's circulation road are injected, and regulate each phase flow rate,
Realize the list parcel of solid ball and wrap up more;
(5) double emulsion generated is collected, it is thus achieved that the double emulsion after parcel solid ball.
Fig. 6 gives and prepares embodiment 1 containing single solid core double emulsion, internal phase syringe pump 1 inject solid core with
And internal phase water/oil solution, subsequently into the ten coaxial circular capillaries of triple channel 9, inject middle here by mesophase syringe pump
Phase fluid, the foreign minister's oil/water solution shear then injected by syringe pump 3, prepare the double emulsion containing single solid core.
1mL/h, 6mL/h (Gu-water-oil);1mL/h, 19mL/h (Gu-oil-water).
Fig. 7 gives and prepares embodiment 2 containing two solid core double emulsions, internal phase syringe pump 1 inject solid core with
And internal phase water/oil solution, subsequently into the ten coaxial circular capillaries of triple channel 9, inject middle here by mesophase syringe pump
Phase fluid, the foreign minister's oil/water solution shear then injected by syringe pump 3, prepare the double emulsion containing single solid core.
1mL/h, 4mL/h (Gu-water-oil);1mL/h, 10mL/h (Gu-oil-water).
Fig. 8 gives and prepares embodiment 3 containing three solid core double emulsions, internal phase syringe pump 1 inject solid core with
And internal phase water/oil solution, subsequently into the ten coaxial circular capillaries of triple channel 9, inject middle here by mesophase syringe pump
Phase fluid, the foreign minister's oil/water solution shear then injected by syringe pump 3, prepare the double emulsion containing single solid core.
1mL/h, 3mL/h (Gu-water-oil);1mL/h, 6mL/h (Gu-oil-water).
Fig. 9 gives and prepares embodiment 4 containing four solid core double emulsions, internal phase syringe pump 1 inject solid core with
And internal phase water/oil solution, subsequently into the ten coaxial circular capillaries of triple channel 9, inject middle here by mesophase syringe pump
Phase fluid, the foreign minister's oil/water solution shear then injected by syringe pump 3, prepare the double emulsion containing single solid core.
1mL/h, 2mL/h (Gu-water-oil);1mL/h, 4mL/h (Gu-oil-water).
The foregoing is only embodiments of the invention, not thereby limit the scope of the claims of the present invention, every utilize this
Equivalent structure or equivalence flow process that bright description and accompanying drawing content are made convert, or are directly or indirectly used in other relevant skills
Art field, is the most in like manner included in the scope of patent protection of the present invention.