CN219653038U - Detachable in-vitro micro-tissue dynamic co-culture device - Google Patents
Detachable in-vitro micro-tissue dynamic co-culture device Download PDFInfo
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- CN219653038U CN219653038U CN202320667087.2U CN202320667087U CN219653038U CN 219653038 U CN219653038 U CN 219653038U CN 202320667087 U CN202320667087 U CN 202320667087U CN 219653038 U CN219653038 U CN 219653038U
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- 238000000338 in vitro Methods 0.000 title claims abstract description 32
- 238000003501 co-culture Methods 0.000 title claims abstract description 31
- 238000003780 insertion Methods 0.000 claims description 25
- 230000037431 insertion Effects 0.000 claims description 25
- 230000004888 barrier function Effects 0.000 claims description 17
- 238000004114 suspension culture Methods 0.000 claims description 13
- 238000007789 sealing Methods 0.000 claims description 11
- 239000012528 membrane Substances 0.000 claims description 7
- 239000004793 Polystyrene Substances 0.000 claims description 3
- 229920007962 Styrene Methyl Methacrylate Polymers 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- ADFPJHOAARPYLP-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;styrene Chemical compound COC(=O)C(C)=C.C=CC1=CC=CC=C1 ADFPJHOAARPYLP-UHFFFAOYSA-N 0.000 claims description 3
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 3
- 229920000515 polycarbonate Polymers 0.000 claims description 3
- 239000004417 polycarbonate Substances 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- 229920002223 polystyrene Polymers 0.000 claims description 3
- SCUZVMOVTVSBLE-UHFFFAOYSA-N prop-2-enenitrile;styrene Chemical compound C=CC#N.C=CC1=CC=CC=C1 SCUZVMOVTVSBLE-UHFFFAOYSA-N 0.000 claims description 3
- 229920000638 styrene acrylonitrile Polymers 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 238000010276 construction Methods 0.000 description 4
- 230000004907 flux Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000012136 culture method Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000013335 3D tissue model Methods 0.000 description 1
- 210000002457 barrier cell Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
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- 230000002572 peristaltic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The utility model discloses a detachable in-vitro micro-tissue dynamic co-culture device, which at least comprises: the carrier is provided with a plurality of column grooves, and each column groove is internally provided with a plurality of clamping grooves for dividing the column groove into a plurality of single-hole structures; and the culture unit is arranged in the single-hole structure and is detachably connected with the carrier. The utility model realizes that various micropores can be independently cultured, can be assembled according to the need in a permutation and combination mode, and forms a flexible and highly customized in-vitro micro-tissue dynamic co-culture device.
Description
Technical Field
The utility model relates to the technical field of tissue culture and microfluidic chips, in particular to a detachable in-vitro micro-tissue dynamic co-culture device.
Background
Along with the rapid development of accurate medicine, an in-vitro 3D tissue culture platform with dynamic, accurate, high flux and low cost is constructed, so that the in-vitro 3D tissue culture platform becomes an urgent requirement for clinical accurate medicine screening. A variety of platforms for in vitro 3D tissue co-culture are currently reported, including pump-driven based culture platforms, submerged co-culture well plates, in vitro barrier culture platforms, gas-liquid interactive culture platforms, and the like. The complex and varied research requirements put higher demands on the flexibility of the dynamic co-culture platform, for example, in constructing a heart-blood brain barrier-skin-liver co-culture system, an immersed tissue culture method, a barrier tissue culture method and a gas-liquid interactive tissue culture method are involved. For such complex co-cultivation modes, it is often necessary to build a cultivation platform in a customized manner, which is costly. A standardized, low-cost culture platform capable of flexibly realizing different culture splices becomes a requirement of complex research.
Disclosure of Invention
The utility model aims to provide a detachable in-vitro micro-tissue dynamic co-culture device, which can realize independent culture among various micropores, and can be assembled as required in a permutation and combination mode to form a flexible and highly customized in-vitro micro-tissue dynamic co-culture device.
The technical scheme adopted by the utility model is as follows:
a detachable in vitro micro-tissue dynamic co-culture device, comprising at least:
the carrier is provided with a plurality of column grooves, and each column groove is internally provided with a plurality of clamping grooves for dividing the column groove into a plurality of single-hole structures;
and the culture unit is arranged in the single-hole structure and is detachably connected with the carrier.
Preferably, a male insertion runner is arranged at one end of the culture unit, a female insertion runner is arranged at the other end of the culture unit, and adjacent culture units are connected end to end through the male insertion runner and the female insertion runner.
Preferably, a sealing ring is further arranged on the outer side of the male insertion flow channel, and a rubber ring is arranged in the sealing ring and used for sealing the joint of the male insertion flow channel and the female insertion flow channel.
Preferably, the male plug is arranged at the top of the male plug flow channel, the female plug is arranged at the top of the female plug flow channel, and the male plug is meshed with the female plug.
Preferably, the male insert and the female insert are engaged in a manner of toothed engagement, latch engagement or snap engagement
Preferably, a clamping groove buckle is arranged at the bottom of the culture unit, and the clamping groove buckle is in clamping connection with the clamping groove.
Preferably, culture micropores are arranged in the culture unit, and the bottom ends of the culture micropores are U-shaped or planar.
Preferably, a suspension culture frame is further connected in the culture micropore, and the suspension culture frame comprises an arc barrier wall and a semi-permeable membrane adhered to the bottom of the arc barrier wall.
Preferably, the left and right side walls of the culture unit are provided with side wall structures with big top and small bottom, and the inclination angle is 0.1-5 degrees.
Preferably, the inclination angle is 1 °.
Preferably, the material of the carrier and the culture unit is one selected from polycarbonate, polystyrene, polymethyl methacrylate, styrene acrylonitrile, and styrene-methyl methacrylate copolymer.
The beneficial effects of the utility model at least comprise:
1. the utility model realizes the multi-pore co-culture with self-defined quantity, and optimizes the limit of the quantity of tissue micropores in a single-pore dynamic co-culture model.
2. The method transfers the original in-vitro multi-tissue dynamic co-culture model based on the microfluidic chip to the size of the microporous plate, discards the defects of complex construction, high cost, standardization degree and small flux of the microfluidic chip, and realizes the construction of the in-vitro multi-tissue dynamic co-culture model with high flux, low cost and high convenience.
3. The utility model is based on a micro-pore plate, and the flow of the micro-fluid is controlled by the swing of the swing bed to provide the hydraulic pressure difference, so that the dynamic and controllable micro-fluid is formed. The method can realize high-flux and low-cost dynamic environment construction, and compared with a peristaltic pump, the method has the advantages of lower cost, more convenient operation and higher flux.
4. The culture unit comprises a plurality of types of in-vitro culture model structures, and provides a standardized culture platform for culturing a plurality of different types of in-vitro 3D tissue models.
5. In the utility model, all types of micropores can be manufactured in a standardized way, so that the construction cost of the in-vitro complex co-culture model is effectively reduced.
Drawings
FIG. 1 is a schematic diagram of a detachable in vitro micro-tissue dynamic co-culture device according to the present utility model;
FIG. 2 is a cross-sectional view of a detachable in vitro micro-tissue dynamic co-culture device according to the present utility model;
FIG. 3 is an enlarged view at A of FIG. 2;
FIG. 4 is a schematic diagram showing the structure of a culture unit according to the present utility model;
FIG. 5 is a schematic diagram of the engagement of male pin 24 and female pin 25 into a toothed engagement according to the present utility model;
FIG. 6 is a schematic diagram of the engagement of male pin 24 and female pin 25 into a latch engagement according to the present utility model;
FIG. 7 is a schematic illustration of the engagement of male pin 24 and female pin 25 into a snap engagement according to the present utility model;
FIG. 8 is a sectional view of a culture unit according to the utility model;
FIG. 9 is a schematic diagram showing the assembly of a culture unit and a suspension culture frame according to the utility model;
FIG. 10 is a schematic diagram showing the structure of a suspension culture frame according to the utility model.
Description of the reference numerals
1-carrier, 11-column groove, 12-clamping groove, 2-culture unit, 21-male insertion runner, 22-female insertion runner, 23-sealing ring, 24-male insertion, 25-female insertion, 26-clamping groove buckle, 27-culture micropore, 3-suspension culture frame, 31-arc barrier wall and 32-semipermeable membrane.
Detailed Description
The following description of at least one exemplary embodiment is merely exemplary in nature and is in no way intended to limit the utility model, its application, or uses. All other embodiments, which can be made by those skilled in the art based on the embodiments of the utility model without making any inventive effort, are intended to be within the scope of the utility model.
Referring to fig. 1-3, a detachable in vitro micro-tissue dynamic co-culture device comprises at least:
the carrier 1 is provided with a plurality of column grooves 11, and each column groove 11 is internally provided with a plurality of clamping grooves 12 for dividing the column groove 11 into a plurality of single-hole structures;
and the culture unit 2 is arranged in the single-hole structure and is detachably connected with the carrier 1.
The carrier 1 is mainly used for fixing the culture unit 2. The culture unit 2 is divided into a submerged culture unit, a barrier culture unit and a low adsorption suspension culture unit according to culture requirements. Each culture unit 2 is an independent module, and can be freely switched and mutually assembled so as to meet the personalized co-culture requirement.
Referring to fig. 4, one end of the culture unit 2 is provided with a male insertion flow channel 21, the other end of the culture unit 2 is provided with a female insertion flow channel 22, and adjacent culture units 2 are connected end to end through the male insertion flow channel 21 and the female insertion flow channel 22.
The outside of the male insertion flow passage 21 is also provided with a sealing ring 23, and a rubber ring is arranged in the sealing ring 23 and used for sealing the joint of the male insertion flow passage 21 and the female insertion flow passage 22.
The cultivation unit 2 is located the public top of inserting runner 21 is provided with the public plug 24 of buckle, the cultivation unit 2 is located the female top of inserting runner 22 is provided with the female 25 of buckle, public plug 24 with female 25 engagement of inserting.
The male plug 24 and the female plug 25 are engaged in a manner of being classified into a toothed engagement, a latch engagement or a snap engagement.
Referring to fig. 4, the male plug 24 and the female plug 25 are engaged in a toothed manner, and the male plug 24 and the female plug 25 are engaged in a single tooth manner;
referring to fig. 5, the male plug 24 and the female plug 25 are engaged with each other in a toothed manner, and the male plug 24 and the female plug 25 are both toothed and engaged with each other;
referring to fig. 6, male insert 24 engages female insert 25 as a latch engagement;
referring to fig. 7, male insert 24 is engaged with female insert 25 as a snap-fit engagement. The bottom of the culture unit 2 is provided with a clamping groove buckle 26, and the clamping groove buckle 26 is clamped with the clamping groove 12.
Culture micropores 27 are arranged in the culture unit 2, and the bottom ends of the culture micropores 27 are U-shaped or planar.
Referring to fig. 8 (a), when the bottom end of the culture micro-hole 27 is planar, it is an immersed culture unit, and the culture micro-hole 27 is TC-treated, which can be used for cell culture and in vitro tissue culture, as in a conventional cell culture well plate.
Referring to fig. 8 (b), when the bottom of the culture micro-hole 27 is U-shaped, it is a low adsorption suspension type culture unit, the culture micro-hole 27 is not TC-treated, and its functionality is similar to that of a common U-shaped culture well plate, and after cells or micro-tissues are seeded into the culture micro-hole 27, the cells and micro-tissues spontaneously aggregate at the dish bottom due to gravity due to the low adsorption plate bottom, and spontaneously form a 3d tissue structure.
Referring to fig. 9-10, a suspension culture frame 3 is further connected in the culture microwell 27, and the suspension culture frame 3 includes a circular arc barrier wall 31 and a semi-permeable membrane 32 adhered to the bottom of the circular arc barrier wall 31. And the suspension culture frame 3 is connected to the culture microwells 27, so that the barrier culture unit can be freely combined with the submerged culture unit or the low-adsorption suspension culture unit to form the barrier culture unit. By culturing barrier cells on the semipermeable membrane 32 in two parts, such as: endothelial cells, epithelial cells, muscle cells, and the like, thereby forming an in vitro biological barrier model.
The left and right side walls of the culture unit 2 are provided with side wall structures with big top and small bottom, and the inclination angle is 0.1-5 degrees.
The tilt angle is 1 °.
The material of the carrier 1 and the culture unit 2 is selected from one of polycarbonate, polystyrene, polymethyl methacrylate, styrene acrylonitrile and styrene-methyl methacrylate copolymer.
The working process of the utility model is described in detail below: when the utility model is used, a plurality of culture units 2 are connected according to the need, the male buckle plug 24 and the female buckle plug 25 are meshed with each other, the male plug runner 21 and the female plug runner 22 are communicated with each other, the rubber ring is embedded into the sealing ring 23 at the meshing position, the air tightness of the communicating position of the runners is effectively ensured, and the clamping groove buckles 26 of the bottom plate of the culture units 2 are meshed with the clamping grooves 12 on the carrier 1 to fix the culture units.
When the bottom of the culture micro-hole 27 is planar, the micro-tissue to be cultured is immersed in the culture unit, and the micro-tissue can be directly inoculated/printed/transferred to the bottom of the dish, and then immersed in the culture medium. When the microporous unit 2 is disassembled, the culture medium is sucked away, the liquid level is below the female plug flow channel 22 in the culture unit 2, then the culture medium is assembled with other culture units 2, and after the assembly is completed, the culture medium is newly added and exceeds the male plug flow channel 21 in the culture unit 2 so as to ensure the full communication between the holes.
When the suspension culture frame 3 is connected to the culture microwells 27, the barrier type culture unit is a barrier type culture unit, and the barrier type culture unit can be freely combined with the submerged type culture unit or the low adsorption suspension type culture unit. Cells or matrix mixed with the cells can be respectively adhered to two sides of the semipermeable membrane 31 in a planting mode, so that a barrier structure is formed, and the upper part and the lower part of the semipermeable membrane 31 can be used for culturing tissue micro-tissues, organoids, cells or the like according to research requirements.
When the bottom end of the culture micro-hole 27 is in a U shape, the culture micro-hole is a low adsorption suspension type culture unit, and tissues or cells are spontaneously deposited at the U-shaped bottom due to gravity after being injected into the culture micro-hole 27, so as to form a 3D culture structure.
And (5) constructing a dynamic culture environment. The carrier with culture micropores is placed on an inclined shaking table to shake, so that a dynamic culture environment can be formed.
The above description is only of the preferred embodiments of the present utility model and is not intended to limit the present utility model, but various modifications and variations can be made to the present utility model by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present utility model should be included in the protection scope of the present utility model.
Claims (10)
1. A detachable in vitro micro-tissue dynamic co-culture device, which is characterized by at least comprising:
the carrier (1) is provided with a plurality of column grooves (11), and each column groove (11) is internally provided with a plurality of clamping grooves (12) for dividing the column groove (11) into a plurality of single-hole structures;
and the culture unit (2) is arranged in the single-hole structure and is detachably connected with the carrier (1).
2. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 1, wherein one end of the culture unit (2) is provided with a male insertion runner (21), the other end of the culture unit (2) is provided with a female insertion runner (22), and adjacent culture units (2) are connected end to end through the male insertion runner (21) and the female insertion runner (22).
3. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 2, wherein a sealing ring (23) is further arranged on the outer side of the male insertion flow channel (21), and a rubber ring is arranged in the sealing ring (23) and is used for sealing the joint of the male insertion flow channel (21) and the female insertion flow channel (22).
4. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 2, wherein the culture unit (2) is provided with a male plug (24) at the top of the male plug flow channel (21), the culture unit (2) is provided with a female plug (25) at the top of the female plug flow channel (22), and the male plug (24) is meshed with the female plug (25).
5. A detachable in vitro micro-tissue dynamic co-culture device according to claim 3, wherein the male insert (24) and the female insert (25) are engaged in a manner which is classified as a toothed engagement, a bayonet engagement or a snap engagement.
6. The detachable in-vitro micro-tissue dynamic co-culture device according to any one of claims 1-5, wherein a clamping groove buckle (26) is arranged at the bottom of the culture unit (2), and the clamping groove buckle (26) is clamped with the clamping groove (12).
7. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 1, wherein culture micro-holes (27) are arranged in the culture unit (2), and the bottom ends of the culture micro-holes (27) are U-shaped or planar.
8. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 7, wherein a suspension culture frame (3) is further connected in the culture micro-holes (27), and the suspension culture frame (3) comprises an arc barrier wall (31) and a semi-permeable membrane (32) adhered to the bottom of the arc barrier wall (31).
9. The detachable in-vitro micro-tissue dynamic co-culture device according to claim 1, wherein the left and right side walls of the culture unit (2) are provided with side wall structures with big top and small bottom, and the inclination angle is 0.1-5 degrees.
10. The detachable in vitro micro-tissue dynamic co-culture device according to claim 1, wherein the material of the carrier (1) and the culture unit (2) is selected from one of polycarbonate, polystyrene, polymethyl methacrylate, styrene acrylonitrile, styrene-methyl methacrylate copolymer.
Priority Applications (1)
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CN202320667087.2U CN219653038U (en) | 2023-03-30 | 2023-03-30 | Detachable in-vitro micro-tissue dynamic co-culture device |
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CN202320667087.2U CN219653038U (en) | 2023-03-30 | 2023-03-30 | Detachable in-vitro micro-tissue dynamic co-culture device |
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