CN105886472A - Patterned substrate for constructing in-vitro tumour model - Google Patents
Patterned substrate for constructing in-vitro tumour model Download PDFInfo
- Publication number
- CN105886472A CN105886472A CN201610314863.5A CN201610314863A CN105886472A CN 105886472 A CN105886472 A CN 105886472A CN 201610314863 A CN201610314863 A CN 201610314863A CN 105886472 A CN105886472 A CN 105886472A
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- Prior art keywords
- tumor model
- patterned substrate
- construct
- pattern structure
- basalis
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 35
- 239000000758 substrate Substances 0.000 title claims abstract description 24
- 238000000338 in vitro Methods 0.000 title abstract description 9
- 210000004027 cell Anatomy 0.000 claims abstract description 19
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000000017 hydrogel Substances 0.000 claims description 19
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 7
- 239000002243 precursor Substances 0.000 claims description 7
- 238000001879 gelation Methods 0.000 claims description 5
- 239000000499 gel Substances 0.000 claims description 4
- 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 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000004698 Polyethylene Substances 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000004793 Polystyrene Substances 0.000 claims description 3
- 229910000831 Steel Inorganic materials 0.000 claims description 3
- 229910001069 Ti alloy Inorganic materials 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 3
- -1 polyethylene Polymers 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- 229920005553 polystyrene-acrylate Polymers 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 239000010959 steel Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 8
- 238000011160 research Methods 0.000 abstract description 6
- 230000003993 interaction Effects 0.000 abstract description 4
- 230000006399 behavior Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 238000012216 screening Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 4
- 210000001082 somatic cell Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 230000000118 anti-neoplastic effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000007877 drug screening Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000008143 early embryonic development Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 238000001259 photo etching Methods 0.000 description 1
- 229920002120 photoresistant polymer Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0693—Tumour cells; Cancer cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1347—Smooth muscle cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2535/00—Supports or coatings for cell culture characterised by topography
- C12N2535/10—Patterned coating
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a patterned substrate for constructing an in-vitro tumour model. The patterned substrate comprises a substrate layer and a patterned structure which is arranged on the substrate layer; the patterned structure forms the in-vitro tumour model on the substrate layer after being subjected to pulling treatment. The in-vitro tumour model constructed on the substrate layer can be used for simulating an in-vivo tumour tissue, so that the cell biological behaviours of tumour cells are researched, and the interactions among cells are observed; the in-vitro tumour model can also be used for screening medicaments and observing the effects of an anti-tumour medicament on the tumour cells in the in-vitro tumour model. According to the patterned substrate for constructing the in-vitro tumour model, the in-vitro tumour model which is prepared by a simple method has the characteristics of simple operation, portability, individuation and the like; an important research platform is provided for precision medicine and translational medicine research.
Description
Technical field
The invention belongs to lab on A Chip processing preparation and biomedicine technical field, be specifically related to a kind of patterned substrate for the outer tumor model of construct.
Background technology
Along with multidisciplinary continuous Cross slot interference such as medical science, physics, chemistry, biologies, create the research field that such as translational medicine and accurate medical science etc. are new.Modern medicine study highlights Basic Research Results and can convert to clinic rapidly, and the feature such as personalization, portability.Traditional based on Petri dish two-dimentional cell training method, its condition of culture differs greatly with internal microenvironment, the function of the tissue level that the body cell of cultivation can not be brought into normal play, and the life-span is relatively short.And zoopery is except costly, the cycle is long, difference in genera, it was predicted that human diseases exists outside error, also there is risk ethically.Marginal external threedimensional model, its structure not only rests on cell level, also relates to the interaction between the interaction between cell and cell, cell and extracellular matrix.External threedimensional model reasonable in design, needs the truth in the most accurate antimer.For early embryonic development, the research of stem cell, the most real structural model can be built；For drug screening, then contribute to more effective, quickly screen medicine, shorten the R&D cycle.
Summary of the invention
It is an object of the invention to application prospect based on above-mentioned external model, and the relative deficiency of prior art, a kind of patterned substrate for the outer tumor model of construct is provided, can the outer tumor model of construct easy, effective, thus the research and development for Tissue Engineering Study and antineoplastic provide platform.
The technical scheme is that and be achieved in that:
Patterned substrate for the outer tumor model of construct of the present invention, is characterized in: including basalis and arrange pattern structure on the base layer, described pattern structure is formed with Vitro Tumor model after lifting processes on the base layer.
Wherein, described basalis is made up of sheet metal or macromolecular material.And, described sheet metal is titanium alloy thin slice or aluminum slice or steel thin slice or other sheet metal.Described macromolecular material is polystyrene or polymethyl methacrylate or polyethylene or other macromolecular material.
Described pattern structure region is set to the area of the pattern that the aqueous solution can adhere to, and the region outside described pattern structure is set to the background area that the aqueous solution can not adhere to.
Described pattern structure may be configured as the graphic structure that arbitrary shape is closed, and described pattern structure can be separately provided be one, or be provided with multiple and form array structure on the base layer.
The area of described pattern structure is 2000 square microns～7500 square millimeters.
Described Vitro Tumor model includes inside and outside two-layer hydrogel, and internal layer hydrogel contains tumour cell, and outer layer hydrogel contains normal body cell.
Described hydrogel comprise can the hydrogel precursor liquid of Rapid gelation, described hydrogel precursor liquid is sodium alginate or gelatin or the polyethylene glycol gel aqueous solution.
The present invention compared with prior art, has the advantage that
The Vitro Tumor model that the present invention builds on the base layer, may be used for the tumor tissues in analogue body, thus the cell behaviors of study tumor cell, the interaction between observation of cell and cell；Can be used for drug screening, observe antineoplastic to the effect of tumour cell in Vitro Tumor model.The present invention prepares Vitro Tumor model with easy method, has the features such as simple to operate, portability, personalization, studies for precisely medical treatment and translational medicine and provide important research platform.
The present invention is further illustrated below in conjunction with the accompanying drawings.
Accompanying drawing explanation
Fig. 1 is the perspective view of the present invention.
Fig. 2 is the planar structure schematic diagram of the present invention.
Detailed description of the invention
As Figure 1-Figure 2, patterned substrate for the outer tumor model of construct of the present invention, including basalis 1 and the pattern structure 2 that is arranged on basalis 1, described pattern structure 2 is formed with Vitro Tumor model 3 after lifting processes on basalis 1.Wherein, described basalis 1 is made up of sheet metal or macromolecular material.When basalis 1 is made up of sheet metal, described sheet metal is titanium alloy thin slice or aluminum slice or steel thin slice or other sheet metal.When basalis 1 is made up of macromolecular material, described macromolecular material is polystyrene or polymethyl methacrylate or polyethylene or other macromolecular material.And, described pattern structure 2 region is set to the area of the pattern that the aqueous solution can adhere to, and the region outside described pattern structure 2 is set to the background area that the aqueous solution can not adhere to.Described pattern structure 2 may be configured as the graphic structure that arbitrary shape is closed, and described pattern structure 2 can be separately provided be one, or be provided with multiple and on basalis 1, form array structure.The area of described pattern structure 2 is 2000 square microns～7500 square millimeters.And, described Vitro Tumor model 3 includes inside and outside two-layer hydrogel, and internal layer hydrogel contains tumour cell, and this tumour cell is Hela cell or MCF7 cell or other type of tumour cell, outer layer hydrogel contains normal body cell, and this normal body cell is including but not limited to SMC cell.Described hydrogel comprise can the hydrogel precursor liquid of Rapid gelation, described hydrogel precursor liquid is the hydrogel precursor liquid of sodium alginate or gelatin or the polyethylene glycol gel aqueous solution or other kind.
The preparation method of the present invention is as follows:
1, the preparation of patterned substrate
Use AutoCAD Software for Design pattern.The method utilizing photoetching, pattern is prepared in face on the base layer.Region outside pattern carries out hydrophobization process to surface so that the aqueous solution cannot adhere to.Further, use acetone to remove photoresist, obtain the surface of patterning；
2, the preparation of Vitro Tumor model
Utilize the method that secondary lifts.First will be patterned into substrate to put into containing lifting in tumour cell solution, containing tumour cell drop inside the base pattern obtained, tumour cell drop is carried out gelation process.Again basalis is put in the solution containing normal somatic cell and lift, containing normal somatic cell drop inside the base pattern obtained, and normal somatic cell drop is carried out gelation process.Containing two kinds of cells in the water gel external model so obtained.
The present invention is described by embodiment, but do not limit the invention, with reference to description of the invention, other changes of the disclosed embodiments, as the professional person for this area is readily apparent that, such change should belong within the scope of the claims in the present invention restriction.
Claims (9)
1. the patterned substrate for the outer tumor model of construct, it is characterized in that: include basalis (1) and the pattern structure (2) being arranged on basalis (1), described pattern structure (2) is formed with Vitro Tumor model (3) after lifting processes on basalis (1).
Patterned substrate for the outer tumor model of construct the most according to claim 1, it is characterised in that: described basalis (1) is made up of sheet metal or macromolecular material.
Patterned substrate for the outer tumor model of construct the most according to claim 2, it is characterised in that: described sheet metal is titanium alloy thin slice or aluminum slice or steel thin slice.
Patterned substrate for the outer tumor model of construct the most according to claim 2, it is characterised in that: described macromolecular material is polystyrene or polymethyl methacrylate or polyethylene.
Patterned substrate for the outer tumor model of construct the most according to claim 1, it is characterized in that: described pattern structure (2) region is set to the area of the pattern that the aqueous solution can adhere to, the region outside described pattern structure (2) is set to the background area that the aqueous solution can not adhere to.
Patterned substrate for the outer tumor model of construct the most according to claim 1, it is characterized in that: described pattern structure (2) may be configured as the graphic structure that arbitrary shape is closed, and described pattern structure (2) can be separately provided be one, or be provided with multiple and form array structure on basalis (1).
Patterned substrate for the outer tumor model of construct the most according to claim 1, it is characterised in that: the area of described pattern structure (2) is 2000 square microns～7500 square millimeters.
Patterned substrate for the outer tumor model of construct the most according to claim 1, it is characterised in that: described Vitro Tumor model (3) includes inside and outside two-layer hydrogel, and internal layer hydrogel contains tumour cell, and outer layer hydrogel contains normal body cell.
Patterned substrate for the outer tumor model of construct the most according to claim 8, it is characterised in that: described hydrogel comprise can the hydrogel precursor liquid of Rapid gelation, described hydrogel precursor liquid is sodium alginate or gelatin or the polyethylene glycol gel aqueous solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610314863.5A CN105886472A (en) | 2016-05-13 | 2016-05-13 | Patterned substrate for constructing in-vitro tumour model |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610314863.5A CN105886472A (en) | 2016-05-13 | 2016-05-13 | Patterned substrate for constructing in-vitro tumour model |
Publications (1)
| Publication Number | Publication Date |
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| CN105886472A true CN105886472A (en) | 2016-08-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610314863.5A Pending CN105886472A (en) | 2016-05-13 | 2016-05-13 | Patterned substrate for constructing in-vitro tumour model |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107058098A (en) * | 2017-03-01 | 2017-08-18 | 北京科技大学 | A kind of device and method of the cell patterning culture based on 3D printing technique |
| CN108823165A (en) * | 2018-04-17 | 2018-11-16 | 广州波奇亚标准及检测技术有限公司 | It is a kind of to change the new method that surface wettability realizes three-dimensional cell cultivation based on laser |
| CN114603846A (en) * | 2022-03-02 | 2022-06-10 | 中山大学 | Method for producing three-dimensional multilayer structure |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101978272A (en) * | 2008-03-27 | 2011-02-16 | 哈佛学院院长等 | Paper-based cellular arrays |
| CN102465119A (en) * | 2010-11-12 | 2012-05-23 | 国家纳米科学中心 | Substrate for cell micropatterning growth as well as preparation method and application thereof |
| CN104178415A (en) * | 2014-08-23 | 2014-12-03 | 吉林大学 | Cell patterning structure, preparation method and application in cell proliferation inhibition |
-
2016
- 2016-05-13 CN CN201610314863.5A patent/CN105886472A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101978272A (en) * | 2008-03-27 | 2011-02-16 | 哈佛学院院长等 | Paper-based cellular arrays |
| CN102465119A (en) * | 2010-11-12 | 2012-05-23 | 国家纳米科学中心 | Substrate for cell micropatterning growth as well as preparation method and application thereof |
| CN104178415A (en) * | 2014-08-23 | 2014-12-03 | 吉林大学 | Cell patterning structure, preparation method and application in cell proliferation inhibition |
Non-Patent Citations (2)
| Title |
|---|
| KANG SUN 等: ""Semi-Egg-Like Heterogeneous Compartmentalization of Cells Controlled by Contact Angle Hysteresis"", 《ADVANCED FUNCTIONAL MATERIALS》 * |
| ZHAOBIN GUO 等: ""Fabrication of Hydrogel with Cell Adhesive Micropatterns for Mimicking the Oriented Tumor-Associated Extracellular Matrix"", 《ACS APPLIED MATERIALS & INTERFACES》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107058098A (en) * | 2017-03-01 | 2017-08-18 | 北京科技大学 | A kind of device and method of the cell patterning culture based on 3D printing technique |
| CN108823165A (en) * | 2018-04-17 | 2018-11-16 | 广州波奇亚标准及检测技术有限公司 | It is a kind of to change the new method that surface wettability realizes three-dimensional cell cultivation based on laser |
| CN108823165B (en) * | 2018-04-17 | 2021-11-16 | 广州波奇亚标准及检测技术有限公司 | Novel method for realizing three-dimensional cell culture by changing surface wettability based on laser |
| CN114603846A (en) * | 2022-03-02 | 2022-06-10 | 中山大学 | Method for producing three-dimensional multilayer structure |
| CN114603846B (en) * | 2022-03-02 | 2023-03-14 | 中山大学 | Method for producing three-dimensional multilayer structure |
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Application publication date: 20160824 |