CN108889353A - A kind of centrifugal microfluidic control device - Google Patents
A kind of centrifugal microfluidic control device Download PDFInfo
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- CN108889353A CN108889353A CN201811099440.1A CN201811099440A CN108889353A CN 108889353 A CN108889353 A CN 108889353A CN 201811099440 A CN201811099440 A CN 201811099440A CN 108889353 A CN108889353 A CN 108889353A
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- chassis
- nozzle
- control device
- collection chamber
- microfluidic control
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- 239000011521 glass Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 239000007921 spray Substances 0.000 claims description 6
- 239000000017 hydrogel Substances 0.000 abstract description 35
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 abstract description 10
- 239000000661 sodium alginate Substances 0.000 abstract description 10
- 235000010413 sodium alginate Nutrition 0.000 abstract description 10
- 229940005550 sodium alginate Drugs 0.000 abstract description 10
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 239000000725 suspension Substances 0.000 abstract description 7
- 239000000969 carrier Substances 0.000 abstract description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 239000007788 liquid Substances 0.000 description 20
- 239000003814 drug Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 238000010586 diagram Methods 0.000 description 7
- 238000005538 encapsulation Methods 0.000 description 7
- 239000000835 fiber Substances 0.000 description 6
- 239000011258 core-shell material Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000003292 glue Substances 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000007590 electrostatic spraying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920001410 Microfiber Polymers 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0052—Preparation of gels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0052—Preparation of gels
- B01J13/0065—Preparation of gels containing an organic phase
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M45/00—Means for pre-treatment of biological substances
- C12M45/22—Means for packing or storing viable microorganisms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/12—Specific details about manufacturing devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
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Abstract
The invention discloses a kind of centrifugal microfluidic control devices comprising：Chassis is provided with multiple circumferentially distributed collection chamber on the chassis；Multiple nozzles on the chassis and circumferentially distributed can be set to, it is connected to inside the outlet of any one of nozzle and a collection chamber, the distance between the outlet of the nozzle and the bottom wall of the collection chamber are greater than zero, and the nozzle is located at the side of the close center chassis of the collection chamber；Actuator, the actuator can drive the chassis to rotate.When using centrifugal microfluidic control device provided by the invention, when driving chassis rotation by actuator, the suspension of sodium alginate soln and cell in multiple nozzles respectively enters in multiple collection chamber, and then can form multiple hydrogel carriers, substantially increases the production efficiency of hydrogel carrier.
Description
Technical field
The present invention relates to biomedical engineering technology fields, more specifically to a kind of centrifugal microfluidic control device.
Background technique
The hydrogel capsule or fiber of micro-meter scale are that field of biomedicine is common a kind of for encapsulating cell, drug
Carrier., can be by stem cell or drug pack in these microcarriers by technological means such as micro-fluidic, electrostatic sprays, then move
It plants progress disease treatment in vivo or carries out external cell culture.
Alginate hydrogel is a kind of encapsulating material being widely used, with cheap, bio-compatibility is good, crosslinking item
The advantages that part is mild.Cell is encapsulated into the microcarrier of alginate hydrogel material can be provided for cell one and in vivo
Similar space structure preferably simulates the proliferation and effect each other of cell.In addition, the loose porous structure of hydrogel is also protected
The mass exchange of cell and external environment is demonstrate,proved.The most common hydrogel carrier for bio-encapsulation is mostly spherical (glue
Capsule) or strip (fiber), and the method for preparing these capsules or fiber is mainly traditional microfluidic methods based on dropping liquid
And electrostatic spraying processes.The principle of these methods is all first to mix cell and hydrogel prepolymer solution, then cut by flowing
It cuts or high pressure is dispersed into the drop of micro-meter scale, finally contact generation with the solution of bivalent cation (such as calcium chloride solution)
Crosslinking, ultimately forms hydrogel.
However, the microfluidic method and high-voltage electrostatic spraying method either based on drop have respective limitation, such as fill
Set that process is complicated and easy to damage, high operation requirements, low output etc..
In conclusion structure is complicated and what production efficiency was low asks for device when how to efficiently solve encapsulation cell or drug
Topic, is current those skilled in the art's urgent problem.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of centrifugal microfluidic control device, the knot of the centrifugal microfluidic control device
The device problem that structure is complicated and production efficiency is low when structure design can efficiently solve encapsulation cell or drug.
In order to achieve the above object, the present invention provides the following technical solutions：
A kind of centrifugal microfluidic control device, including：
Chassis is provided with multiple circumferentially distributed collection chamber on the chassis；
Multiple nozzles on the chassis and circumferentially distributed, the outlet of any one of nozzle and one can be set to
Connection inside a collection chamber, the distance between the outlet of the nozzle and the bottom wall of the collection chamber are greater than zero, and described
Nozzle is located at the side of the close center chassis of the collection chamber；
Actuator, the actuator can drive the chassis to rotate.
Preferably, in above-mentioned centrifugal microfluidic control device, the chassis is disk, and multiple collection chamber are along the chassis
Circumferential direction be uniformly distributed, multiple nozzles are uniformly distributed along the circumferential direction on the chassis.
Preferably, in above-mentioned centrifugal microfluidic control device, multiple holding tanks for being used to accommodate nozzle are provided on the chassis,
The depth of the holding tank is less than the depth of the collection chamber.
Preferably, in above-mentioned centrifugal microfluidic control device, the nozzle is single outlet nozzle, and the diameter of its outlet is less than
1mm。
Preferably, in above-mentioned centrifugal microfluidic control device, the nozzle is double outlet nozzles, and double outlet nozzles include interior
Two outlets of chamber and exocoel, double outlet nozzles are connected to inner cavity and exocoel respectively, and two outlets of double outlet nozzles are coaxial
Setting.
Preferably, in above-mentioned centrifugal microfluidic control device, the quantity on the chassis is multiple, and multiple chassis stackings are set
It sets, the actuator drives multiple chassis rotations jointly.
Preferably, described including the first chassis and the second chassis in multiple chassis in above-mentioned centrifugal microfluidic control device
Nozzle on first chassis is single outlet nozzle；Nozzle on second chassis is double outlet nozzles, double outlet nozzles
Including inner cavity and exocoel, two outlets of double outlet nozzles are connected to inner cavity and exocoel respectively, and two of double outlet nozzles go out
Mouth coaxial arrangement.
Preferably, in above-mentioned centrifugal microfluidic control device, it is provided with 5 collection chamber on first chassis and 5 lists go out
Mouth nozzle；
3 collection chamber and 3 double outlet nozzles are provided on second chassis.
Preferably, in above-mentioned centrifugal microfluidic control device, the material on the chassis is organic glass.
Preferably, in above-mentioned centrifugal microfluidic control device, the collection chamber is sector-shaped compartments.
When using centrifugal microfluidic control device provided by the invention, nozzle is single outlet nozzle, then uses pipettor to nozzle
Solution cavity in be added sodium alginate soln and cell suspension, then nozzle is fixed on chassis.Simultaneously in collecting chamber
Indoor addition calcium chloride solution.Then, chassis and nozzle rotation thereon are driven using actuator, the liquid in the solution cavity of nozzle
Body is crosslinked since centrifugal action is sprayed onto collection chamber and contacts with calcium chloride solution through the outlet of nozzle, forms hydrogel
Carrier.
From the foregoing, it will be observed that when using centrifugal microfluidic control device provided by the invention, it is more when driving chassis rotation by actuator
The suspension of sodium alginate soln and cell in a nozzle respectively enters in multiple collection chamber, and then can form multiple water
Gel carrier substantially increases the production efficiency of hydrogel carrier.In addition, centrifugal microfluidic control apparatus structure letter provided by the invention
Single, cost is relatively low, and operation requires low, can simply and efficiently realize the multi-form encapsulation of cell or drug, can be widely applied
In fields such as cell 3D culture, drug controlled release, cell transplantations.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
It obtains other drawings based on these drawings.
Fig. 1 is the structural schematic diagram on the first chassis provided in an embodiment of the present invention；
Fig. 2 is the structural schematic diagram of single outlet nozzle provided in an embodiment of the present invention；
Fig. 3 is the first chassis provided in an embodiment of the present invention and the schematic diagram that single outlet nozzle cooperates；
Fig. 4 is the structural schematic diagram on the second chassis provided in an embodiment of the present invention；
Fig. 5 is the structural schematic diagram of double outlet nozzles provided in an embodiment of the present invention；
Fig. 6 is the schematic diagram on the second chassis provided in an embodiment of the present invention and double outlet nozzle cooperations；
Fig. 7 is the structural schematic diagram of centrifugal microfluidic control device provided in an embodiment of the present invention；
Fig. 8 a is a kind of hydrogel carrier of the form provided in an embodiment of the present invention formed using single outlet nozzle；
Fig. 8 b is the hydrogel carrier of another form provided in an embodiment of the present invention formed using single outlet nozzle；
Fig. 9 a is a kind of hydrogel carrier of the form provided in an embodiment of the present invention formed using double outlet nozzles；
Fig. 9 b is the hydrogel carrier of another form provided in an embodiment of the present invention formed using double outlet nozzles.
In Fig. 1-9b：
The first chassis 1-, 2- holding tank, 3- collection chamber, 4- glass plate, the single outlet 5- nozzle, the second chassis 6-, 7- are bis-
Outlet nozzle, 7a- exocoel inlet tube, the inner cavity 7b- inlet tube, 8- actuator, 9- fixed screw, 10- fixture nut, a- hydrogel
Shell, b- liquid phase core, c- cell or drug.
Specific embodiment
The purpose of the present invention is to provide a kind of centrifugal microfluidic control device, the structure design of the centrifugal microfluidic control device can be with
The device problem that structure is complicated and production efficiency is low when efficiently solving encapsulation cell or drug.
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
In the description of the present invention, it is to be understood that, term " on ", "lower", "front", "rear", " left side " and " right side " etc. refer to
The orientation or positional relationship shown is to be based on the orientation or positional relationship shown in the drawings, and is merely for convenience of the description present invention and simplifies
Description, rather than the position of indication or suggestion meaning or element must have particular orientation, be constituted and operated with specific orientation,
Therefore it should not be understood as limitation of the invention.In addition, term " first ", " second " are used for description purposes only, and should not be understood as
Indication or suggestion relative importance.
Fig. 1-Fig. 7 is please referred to, centrifugal microfluidic control device provided by the invention includes chassis, actuator 8 and multiple nozzles.Its
In, multiple collection chamber 3 are provided on chassis, and multiple collection chamber 3 are along the circumferentially distributed of chassis.Carry out cell or medicine
When the encapsulation of object, collection chamber 3 is for holding bivalent cation solution such as calcium chloride solution, in order to make bivalent cation solution
It is crosslinked as calcium chloride solution is contacted with sodium alginate soln, ultimately forms hydrogel.
Multiple nozzles can be arranged on chassis, and multiple nozzles are along the circumferentially distributed of chassis.Any one nozzle
Outlet and a collection chamber 3 inside be connected to, i.e., multiple nozzles it is identical with multiple 3 quantity of collection chamber and correspond.It is right
It in the nozzle and collection chamber 3 answered, is connected to inside the outlet of nozzle and collection chamber 3, and the outlet of nozzle and collection chamber 3
The distance between bottom wall is greater than zero.I.e. when chassis is laid flat, in corresponding nozzle and collection chamber 3, the outlet of nozzle, which is higher than, is received
Collect the bottom wall setting of chamber 3, so by adjusting the liquid level height of the calcium chloride solution of collection chamber 3, and then may be implemented to adjust
The outlet of whole nozzle is away from the vertical distance between the liquid level of calcium chloride solution.Liquid level of the outlet of nozzle away from calcium chloride solution at this
Between vertical distance be nozzle outlet center line away from the vertical distance between the liquid level of calcium chloride solution.In addition, spray
Mouth is located at the side of the close center chassis of collection chamber 3, i.e. the nozzle inside that is located at collection chamber 3.Nozzle include outlet and
With the solution cavity of outlet.
Actuator 8 can drive chassis to rotate, and actuator 8 drives chassis to surround its center rotating.
When using centrifugal microfluidic control device provided by the invention, nozzle is single outlet nozzle 5, then uses pipettor to nozzle
Solution cavity in be added sodium alginate soln and cell suspension, then nozzle is fixed on chassis.Simultaneously in collecting chamber
Calcium chloride solution is added in room 3.Then, chassis and nozzle rotation thereon are driven using actuator 8, in the solution cavity of nozzle
Liquid is crosslinked since centrifugal action is sprayed onto collection chamber 3 and contacts with calcium chloride solution through the outlet of nozzle, forms water
Gel carrier.
From the foregoing, it will be observed that when using centrifugal microfluidic control device provided by the invention, when driving chassis rotation by actuator 8,
The suspension of sodium alginate soln and cell in multiple nozzles respectively enters in multiple collection chamber 3, and then can be formed more
A hydrogel carrier substantially increases the production efficiency of hydrogel carrier.In addition, centrifugal microfluidic control device knot provided by the invention
Structure is simple, and cost is relatively low, and operation requires low, can simply and efficiently realize the multi-form encapsulation of cell or drug, can be extensive
Applied to fields such as cell 3D culture, drug controlled release, cell transplantations.
In above-described embodiment, groove can be opened up on chassis, and lid sets cover board, groove and cover board at the notch of groove
Collection chamber 3 is surrounded jointly.Cover board can only cover the part of the notch of groove, to form semi open model collection chamber 3.
The material on chassis can be organic glass material, and cover board may be glass plate 4.Specifically, it can choose 10mm
The organic glass of left and right is processed to form chassis, and the depth of groove is not limited thereto in 7mm or so.Cover board can be by organic
Glass cement is bonded on chassis.Certainly, chassis can also be not limited thereto for other materials.
In one embodiment, chassis can be disk, and certain chassis may be square plate or other shapes, herein not
It limits.
Multiple collection chamber 3 are uniformly distributed along the circumferential direction on chassis, while multiple nozzles are also along the circumferential uniform of chassis
Distribution.So that the stress on chassis is more balanced, entire centrifugal microfluidic control device is more stable.
For the ease of installation nozzle, multiple holding tanks 2 for being used to accommodate nozzle can be set on chassis, it so will be multiple
Nozzle is respectively embedded into the positioning that can be realized in multiple holding tanks 2 to nozzle.Further, the depth of holding tank 2, which is less than, collects
The depth of chamber 3, so ensure that has difference in height between the outlet of nozzle and collection chamber 3.Sea in nozzle in order to prevent
The bottom wall of the suspension flow of solution of sodium alginate and cell, above-mentioned holding tank 2 can be along the direction for moving closer to collection chamber 3
It gradually decreases.
Certainly, nozzle can also be bonded on chassis by glue, or be fixed on chassis by screw etc., herein not
It limits.
In the first embodiment, nozzle be single outlet nozzle 5, single outlet nozzle 5 include outlet and with outlet
Solution cavity.Single outlet nozzle 5 mainly for the production of one pack system microcarrier.When using above-mentioned single outlet nozzle 5, pipettor is used
The suspension of sodium alginate soln and cell is added into the solution cavity of single outlet nozzle 5, is then fixed on single outlet nozzle 5
It is prevented in holding tank 2 on chassis.Calcium chloride solution is added in collection chamber 3 simultaneously.Then, it is driven using actuator 8
Chassis and nozzle rotation thereon, liquid in the solution cavity of nozzle through the outlet of nozzle are sprayed onto collection chamber due to centrifugal action
It contacts in 3 and with calcium chloride solution and crosslinks, form hydrogel carrier.
It should be noted that the liquid level by adjusting the calcium chloride solution of collection chamber 3 is high in the first above-mentioned embodiment
It is low, and then the outlet of adjustment single outlet nozzle 5 may be implemented away from the vertical distance between the liquid level of calcium chloride solution, single outlet spray
The outlet of mouth 5 will directly determine the one pack system hydrogel carrier generated away from the vertical distance size between the liquid level of calcium chloride solution
Form.Under surface tension and the collective effect of centrifugal force, sodium alginate soln is gathered into drop in jet expansion, most laggard
Enter and is cross-linked to form hydrogel microsphere in calcium chloride solution.When the outlet of single outlet nozzle 5 is away from perpendicular between calcium chloride solution liquid level
When straight distance is greater than 0 but is less than 5mm, certain deformation can occur for the form of microcarrier, can not formation rule spherical shape, work as distance
When greater than 5mm, the microcarrier of generation is in spherical shape with good uniformity, as shown in Figure 8 a.
When the vertical distance between liquid level of the outlet of single outlet nozzle 5 away from calcium chloride solution is less than or equal to zero, nozzle
Outlet contacted with calcium chloride solution, the liquid that the outlet of single outlet nozzle 5 sprays when centrifugation continuously enters calcium chloride solution
And crosslink, the microfibre of cell-hydrogel is ultimately formed, as shown in Figure 8 b.
In the first above-mentioned embodiment, multiple single outlet nozzles 5 are arranged on chassis, and multiple single outlet nozzles 5 go out
Mouth diameter can be identical or not identical.By changing the outlet diameter and centrifugation rate of single outlet nozzle 5, can be generated not
With the hydrogel microsphere or fiber of size.Preferably, when centrifugation rate is between 1000-3500r/min, the hydrogel of generation is micro-
The diameter of ball is generally between 100-300um.
In the first above-mentioned embodiment, the outlet diameter of single outlet nozzle 5 is less than 1mm.Preferably, single outlet nozzle 5
Outlet diameter is between tens to several hundred microns.
In second of embodiment, nozzle is double outlet nozzles 7, and double outlet nozzles 7 include inner cavity and exocoel, wherein inner cavity
It is not connected to independently of each other between exocoel.Two outlets of double outlet nozzles 7 are connected to inner cavity and exocoel respectively, i.e., inner cavity is molten
Liquid is sprayed from one outlet, and the solution of exocoel is discharged from another outlet.Also, two outlets of double outlet nozzles 7 are coaxially set
It sets, i.e., it is circle that one outlet, which is another outlet of annular, and ring exit is arranged around round exit, annular outlet and exocoel
Connection, circular outlet are connected to inner cavity, i.e., ring exit is outer vent, and round exit is inner outlet.The two of double outlet nozzles 7
A concordant setting in outlet, i.e., two outlets of double outlet nozzles 7 are concordant on outlet axial direction.
Double outlet nozzles 7 are mainly used for the microcarrier of core-shell structure.It is intracavitary outside to add when using above-mentioned double outlet nozzles 7
Enter hydrogel prepolymer such as sodium alginate soln, inside phase solution such as carboxymethylcellulose sodium solution in intracavitary addition.Then will
Nozzle is fixed on chassis, while appropriate calcium chloride solution being added in collection chamber 3, drives chassis to rotate using actuator 8.
Under the influence of centrifugal force, the solution of the hydrogel prepolymer of exocoel and inner cavity forms the drop or fiber with core-shell structure,
And then the microcarrier for ultimately forming hydrogel is crosslinked after contacting with calcium chloride solution.
In above-mentioned second of embodiment, the viscosity of inner cavity solution determines to generate the form of carrier, if inner cavity solution is viscous
The lower suspension such as cell and culture medium is spent, then interior exocoel solution can spray into strips when being centrifuged, and then it is molten to drop down onto sodium chloride
In liquid, the aquagel fibre that strip has core-shell structure is generated, as shown in figure 9b, wherein outer layer is the shell of hydrogel, internal layer
It is cell suspending liquid.If the suspension of the viscosity of inner cavity solution higher such as cell and carboxymethylcellulose sodium solution, is centrifuged
When interior exocoel solution can be gathered into drop in nozzle tip, and then drop down onto sodium chloride solution, can generate with core-shell structure
Microcapsules, as illustrated in fig. 9, wherein outer layer is hydrogel shell a, and internal layer is liquid phase core b, and cell or drug c are suspended in liquid phase core
In b.
In above-mentioned second of embodiment, between the center and calcium chloride solution liquid level of two outlets of double outlet nozzles 7
Vertical distance is maintained at 4-6mm, specifically may remain in 5mm.In addition, going out in two outlets of double outlet nozzles 7
The outer diameter of mouth can be 300-900 μm, and the diameter of inner outlet can be 100-250 μm.Preferably, two of double outlet nozzles 7
The outer diameter of outer vent can be 600 μm in outlet, and the diameter of inner outlet can be 160 μm.Certainly, two of double outlet nozzles 7
The diameter of the outer diameter of outer vent and inner outlet can adjust according to the actual situation in outlet, be not limited thereto.
In above-mentioned second of embodiment, centrifugation rate is between 800-1300r/min.
In above-mentioned second of embodiment, the exocoel feed liquor being connected to its exocoel can be set on the side wall of double outlet nozzles 7
Pipe 7a, exocoel inlet tube 7a can be hose.Holding tank 2 can also accommodate exocoel inlet tube 7a.The end of double outlet nozzles 7 can
Inner cavity inlet tube 7b, i.e., one end setting inner cavity inlet tube 7b of double outlet nozzles 7 exported originally is arranged.
It should be noted that the shape of holding tank 2 can be different in the first embodiment and in second embodiment.First
In embodiment, holding tank 2 is matched with single outlet nozzle 5；In second embodiment, holding tank 2 is matched with double outlet nozzles 7.So
Nozzle is mounted on chassis, does not need glue and can be with easy removal nozzle.
In order to further increase, the formation efficiency of hydrogel carrier, the quantity on chassis is multiple, and the stacking of multiple chassis is set
It sets, actuator 8 drives multiple chassis to rotate jointly.More hydrogel carriers so once can be generated.Two adjacent bottoms
There is gap, in order to observe between disk.
Furthermore it is possible to which chassis is mounted on actuator 8 by fixed screw 9 and fixture nut 10.Actuator 8 includes electricity
Machine and the panel being connect with the output end of motor.Chassis is mounted on panel, motor driven panel rotation and then drive chassis turn
It is dynamic.Fixed screw 9 pass through multiple chassis, fixture nut 10 and fixed screw 9 cooperation realization panel and chassis it is relatively fixed.
As shown in fig. 7, including the first chassis 1 and the second chassis 6, the first bottom in multiple chassis in the third embodiment
Nozzle on disk 1 is single outlet nozzle 5.Nozzle on second chassis 6 is double outlet nozzles 7, double outlet nozzles 7 include inner cavity and
Two outlets of exocoel, double outlet nozzles 7 are connected to inner cavity and exocoel respectively, and two outlets of double outlet nozzles 7 are coaxially set
It sets.Such actuator 8 drives the first chassis 1 and the second chassis 6 to rotate simultaneously, raw using the first the One On The Chassis single outlet nozzle 5
At multiple one pack system hydrogel carriers, carried using the hydrogel that double outlet nozzles 7 on the second chassis 6 generate multiple core-shell structures
Body.A variety of hydrogel carriers are disposably generated so set, realizing, easy to operate and high production efficiency.
Further, 5 collection chamber 3 and 5 single outlet nozzles 5 can be set on the first chassis 1；Second chassis 6
On be provided with the double outlet nozzles 7 of 3 collection chamber 3 and 3.The outlet diameter of above-mentioned 5 single outlet nozzles 5 can be respectively 60
μm, 90 μm, 160 μm, 210 μm and 250 μm.The outer diameter of outer vent can be 600 μ in two outlets of above-mentioned double outlet nozzles 7
M, the diameter of inner outlet can be 160 μm.
In any embodiment, outer vent in the outlet diameter of single outlet nozzle 5, two of double outlet nozzles 7 outlets
The outlet of the diameter of inner outlet, chassis revolving speed rate and nozzle is molten away from calcium chloride in outer diameter, two of double outlet nozzles 7 outlets
Vertical distance between the liquid level of liquid can be adjusted according to actual needs, be not limited thereto.
Collection chamber 3 on chassis can be sector-shaped compartments, and certainly, collection chamber 3 can also be other arbitrary shapes,
It is not limited thereto.
It is emphasized that in the preparation process of microcarrier, common micro-fluidic chip method, to the treatment effeciency of sample
Tens ul/min magnitudes are typically limited to, and centrifugal microfluidic control device of the present invention, treatment effeciency can be easily reached
10ml/min magnitude.And it is noted that device expansion according to the present invention is extremely strong, increase chassis can be passed through
The quantity of size and nozzle increases the stacking between chassis, and the efficiency that processing is greatly improved reaches several hundred mL/min, and processing speed is
At least 1000 times of traditional microfluidic chip.
Each embodiment in this specification is described in a progressive manner, the highlights of each of the examples are with other
The difference of embodiment, the same or similar parts in each embodiment may refer to each other.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
Claims (10)
1. a kind of centrifugal microfluidic control device, which is characterized in that including：
Chassis is provided with multiple circumferentially distributed collection chamber (3) on the chassis；
Multiple nozzles on the chassis and circumferentially distributed, the outlet of any one of nozzle and a receipts can be set to
Collect connection inside chamber (3), the distance between the outlet of the nozzle and the bottom wall of the collection chamber (3) are greater than zero, and institute
State the side that nozzle is located at the close center chassis of the collection chamber (3)；
Actuator (8), the actuator (8) can drive the chassis to rotate.
2. centrifugal microfluidic control device according to claim 1, which is characterized in that the chassis is disk, and multiple collections
Chamber (3) is uniformly distributed along the circumferential direction on the chassis, and multiple nozzles are uniformly distributed along the circumferential direction on the chassis.
3. centrifugal microfluidic control device according to claim 1, which is characterized in that be provided on the chassis multiple for holding
The holding tank (2) of nozzle is set, the depth of the holding tank (2) is less than the depth of the collection chamber (3).
4. centrifugal microfluidic control device according to claim 1, which is characterized in that the nozzle is single outlet nozzle (5), and
Its diameter exported is less than 1mm.
5. centrifugal microfluidic control device according to claim 1, which is characterized in that the nozzle is double outlet nozzles (7), institute
Stating double outlet nozzles (7) includes inner cavity and exocoel, and two outlets of double outlet nozzles (7) are connected to inner cavity and exocoel respectively, and
Two outlets of double outlet nozzles (7) are coaxially disposed.
6. centrifugal microfluidic control device according to claim 1, which is characterized in that the quantity on the chassis is multiple and more
A chassis is stacked, and the actuator (8) drives multiple chassis rotations jointly.
7. centrifugal microfluidic control device according to claim 6, which is characterized in that include the first chassis in multiple chassis
(1) and the second chassis (6), the nozzle on first chassis (1) is single outlet nozzle (5)；Spray on second chassis (6)
Mouth is double outlet nozzles (7), and double outlet nozzles (7) include inner cavity and exocoel, two outlets difference of double outlet nozzles (7)
It is connected to inner cavity and exocoel, and two outlets coaxial arrangement of double outlet nozzles (7).
8. centrifugal microfluidic control device according to claim 7, which is characterized in that be provided with 5 on first chassis (1)
Collection chamber (3) and 5 single outlet nozzles (5)；
3 collection chamber (3) and 3 double outlet nozzles (7) are provided on second chassis (6).
9. centrifugal microfluidic control device according to claim 1, which is characterized in that the material on the chassis is organic glass.
10. centrifugal microfluidic control device according to claim 1, which is characterized in that the collection chamber (3) is fan-shaped chamber
Room.
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| CN201811099440.1A CN108889353A (en) | 2018-09-20 | 2018-09-20 | A kind of centrifugal microfluidic control device |
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| CN201811099440.1A CN108889353A (en) | 2018-09-20 | 2018-09-20 | A kind of centrifugal microfluidic control device |
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| CN111434385A (en) * | 2019-01-14 | 2020-07-21 | 北京博奥晶典生物技术有限公司 | Misplug-proof microfluidic chip centrifugal tray and use method thereof |
| CN114231397A (en) * | 2021-12-21 | 2022-03-25 | 中国医科大学 | High-throughput drug testing centrifugal microfluidic system and use method thereof |
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| CN108169317A (en) * | 2017-12-20 | 2018-06-15 | 南京大学 | A kind of sodium alginate drop auxiliary living matter mass spectrum sample preparation and the method for ionization |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111434385A (en) * | 2019-01-14 | 2020-07-21 | 北京博奥晶典生物技术有限公司 | Misplug-proof microfluidic chip centrifugal tray and use method thereof |
| CN111434385B (en) * | 2019-01-14 | 2022-04-12 | 北京博奥晶典生物技术有限公司 | Misplug-proof microfluidic chip centrifugal tray and use method thereof |
| CN114231397A (en) * | 2021-12-21 | 2022-03-25 | 中国医科大学 | High-throughput drug testing centrifugal microfluidic system and use method thereof |
| CN114231397B (en) * | 2021-12-21 | 2024-02-23 | 中国医科大学 | Centrifugal microfluidic system for high-flux drug testing and application method thereof |
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Application publication date: 20181127 |