CN118240437A - Polymer coated glass substrate - Google Patents
Polymer coated glass substrate Download PDFInfo
- Publication number
- CN118240437A CN118240437A CN202311480702.XA CN202311480702A CN118240437A CN 118240437 A CN118240437 A CN 118240437A CN 202311480702 A CN202311480702 A CN 202311480702A CN 118240437 A CN118240437 A CN 118240437A
- Authority
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- China
- Prior art keywords
- polymer
- glass substrate
- coated glass
- elastic modulus
- polymer layer
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229920000642 polymer Polymers 0.000 title claims abstract description 130
- 239000011521 glass Substances 0.000 title claims abstract description 85
- 239000000758 substrate Substances 0.000 title claims abstract description 68
- 239000007864 aqueous solution Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000000178 monomer Substances 0.000 claims description 24
- 229920001577 copolymer Polymers 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 7
- 210000004027 cell Anatomy 0.000 abstract description 45
- 206010028980 Neoplasm Diseases 0.000 abstract description 18
- 201000011510 cancer Diseases 0.000 abstract description 18
- 210000000601 blood cell Anatomy 0.000 abstract description 10
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000000034 method Methods 0.000 description 18
- 239000000523 sample Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229920001477 hydrophilic polymer Polymers 0.000 description 12
- 238000000418 atomic force spectrum Methods 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 8
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 210000001124 body fluid Anatomy 0.000 description 5
- 239000010839 body fluid Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 229920001519 homopolymer Polymers 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000005361 soda-lime glass Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WMWLMWRWZQELOS-UHFFFAOYSA-N bismuth(III) oxide Inorganic materials O=[Bi]O[Bi]=O WMWLMWRWZQELOS-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- -1 etc.) Substances 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000005499 meniscus Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 229920000307 polymer substrate Polymers 0.000 description 2
- 229920000193 polymethacrylate Polymers 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- LHENQXAPVKABON-UHFFFAOYSA-N 1-methoxypropan-1-ol Chemical compound CCC(O)OC LHENQXAPVKABON-UHFFFAOYSA-N 0.000 description 1
- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 229910020410 SiO2—B2O3—PbO Inorganic materials 0.000 description 1
- 229910020443 SiO2—PbO—B2O3 Inorganic materials 0.000 description 1
- 239000006087 Silane Coupling Agent Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- PILOURHZNVHRME-UHFFFAOYSA-N [Na].[Ba] Chemical compound [Na].[Ba] PILOURHZNVHRME-UHFFFAOYSA-N 0.000 description 1
- KSHPUQQHKKJVIO-UHFFFAOYSA-N [Na].[Zn] Chemical compound [Na].[Zn] KSHPUQQHKKJVIO-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000005354 aluminosilicate glass Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C17/00—Surface treatment of glass, not in the form of fibres or filaments, by coating
- C03C17/28—Surface treatment of glass, not in the form of fibres or filaments, by coating with organic material
- C03C17/32—Surface treatment of glass, not in the form of fibres or filaments, by coating with organic material with synthetic or natural resins
- C03C17/324—Polyesters
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D133/00—Coating compositions based on homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Coating compositions based on derivatives of such polymers
- C09D133/04—Homopolymers or copolymers of esters
- C09D133/14—Homopolymers or copolymers of esters of esters containing halogen, nitrogen, sulfur or oxygen atoms in addition to the carboxy oxygen
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Geochemistry & Mineralogy (AREA)
- Coating Of Shaped Articles Made Of Macromolecular Substances (AREA)
Abstract
The invention provides a polymer coated glass substrate capable of inhibiting capturing normal cells such as blood cells and selectively capturing specific cells such as cancer cells. A polymer-coated glass substrate, wherein a polymer layer is formed on the surface of the glass substrate, and the elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
Description
Technical Field
The present invention relates to a polymer coated glass substrate.
Background
In order to produce a device for capturing specific cells (blood cells, cancer cells existing in blood or body fluid, etc.) in blood or body fluid, a technique of coating (coating) a specific polymer on a surface of a substrate has been proposed.
However, it is possible that the blood cells are trapped while specific cells such as cancer cells are trapped on the surface of the substrate. Accordingly, it is desirable to provide a polymer-coated substrate capable of more selectively capturing specific cells such as cancer cells and inhibiting capturing normal cells such as blood cells.
Disclosure of Invention
[ Problem ] to be solved by the invention
The present invention has been made to solve the above problems, and an object of the present invention is to provide a polymer-coated glass substrate capable of suppressing the capture of normal cells such as blood cells and selectively capturing specific cells such as cancer cells.
[ Means for solving the problems ]
The present invention relates to a polymer-coated glass substrate, wherein a polymer layer is formed on the surface of the glass substrate, and the elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
[ Effect of the invention ]
According to the present invention, since the glass substrate is coated with the polymer, and the polymer layer is formed on the surface of the glass substrate, the elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less, and thus normal cells such as blood cells can be inhibited from being trapped, and specific cells such as cancer cells can be selectively trapped. Therefore, the polymer-coated glass substrate is expected to improve the capturing performance of specific cells such as cancer cells.
Detailed Description
The present invention is a polymer-coated glass substrate in which a polymer layer is formed on the surface of a glass substrate, wherein the elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
The number of tumor cells (such as cancer cells) in a body fluid such as tumor cells (several to several hundred tumor cells/1 mL of blood) entering the blood circulation is very small, and it is considered important to capture as many tumor cells as possible present in the collected body fluid for examination. The polymer layer surface of the polymer-coated glass substrate of the present invention has an elastic modulus of 1.20MPa or less in water or an aqueous solution. It is known that specific cells such as cancer cells are generally softer than normal cells such as blood cells. This is related to the movement of a specific cell such as a cancer cell through a gap by greatly deforming the shape of the cell. Therefore, normal cells such as hard blood cells, which are hard to deform, are hard to be trapped by the polymer substrate with a soft surface. On the other hand, specific cells such as cancer cells having deformability are obtained, and even a polymer substrate having a soft surface is easily captured. Therefore, by measuring the number of tumor cells trapped in the polymer layer of the polymer-coated glass substrate of the present invention, the number of tumor cells in the body fluid can be determined, and it is expected that the effect of cancer treatment and the like can be confirmed. Further, by culturing the captured tumor cells and confirming the effect of the anticancer agent or the like with the cells cultured thereby, the effect of the anticancer agent or the like can be confirmed in vitro before administration of the anticancer agent or the like, and the selection of the anticancer agent or the like can be facilitated. Further gene analysis of the captured tumor cells facilitates selection of anticancer agents and the like.
The polymer-coated glass substrate has a polymer layer formed on the surface of the glass substrate, and the elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
The elastic modulus is preferably 0.80MPa or less, more preferably 0.50MPa or less, and even more preferably 0.30MPa or less, from the viewpoint of being able to suppress the capture of normal cells such as blood cells and the selective capture of specific cells such as cancer cells. The lower limit is not particularly limited, but is preferably 0.01MPa or more, more preferably 0.05MPa or more, and still more preferably 0.07MPa or more.
The elastic modulus in water or an aqueous solution can be adjusted by changing the molecular weight or film thickness of the polymer forming the polymer layer. Specifically, if the molecular weight of the polymer increases, the elastic modulus tends to increase, and if the film thickness of the polymer layer increases, the elastic modulus tends to increase.
The elastic modulus in water or an aqueous solution may be adjusted by subjecting the glass substrate to a surface treatment such as a primer treatment or a silane coupling agent treatment in advance. Specifically, when the polymer layer is formed on the surface of the surface-treated glass substrate, the elastic modulus tends to increase.
In addition, in the present specification, unless otherwise specified, the elastic modulus in water or in an aqueous solution refers to an elastic modulus in water or in an aqueous solution measured using an Atomic Force Microscope (AFM).
An Atomic Force Microscope (AFM) is one type of scanning probe microscope, and is a microscope that detects a force acting between atoms of a sample and a probe. The probe is attached to the tip of a cantilever (cantilever spring), and the force (bending amount) acting on the cantilever is measured while changing the distance between the sample and the probe, thereby obtaining a curve (force curve) depicting the relationship between the two. By analyzing the force curve, the elastic modulus (hardness) of the sample surface can be obtained, and the elastic modulus can be measured at the nano level. The method for determining the elastic modulus of the sample surface by measuring the force curve is known to those skilled in the art, and the elastic modulus can be determined by such a known method.
Examples of the method for calculating the elastic modulus from the force curve include a method for calculating the elastic modulus by fitting (fitting) a force curve by JKR (Johnson-Kendall-Roberts) theory. In JKR theory, assuming that the agglutination energy is w, the following formulas (1) and (2) represent the force F applied to the cantilever and the sample deformation δ.
[ Number 1]
Where a represents the radius of the contact line between the probe and the sample, R represents the radius of curvature of the probe tip, and K represents the elastic modulus.
The elastic modulus can be obtained by measuring the F-delta curve obtained from the force curve and fitting using the formulas (1) and (2).
Here, the elastic modulus in water or an aqueous solution specifically refers to a measured value measured by the following method.
The measurement value in water or an aqueous solution can be measured by dropping water or an aqueous solution onto the surface of the sample to form droplets (convex meniscus) and measuring the droplets by AFM.
As the aqueous solution, for example, phosphate Buffered Saline (PBS) is suitably used.
The elastic modulus of the sample (surface of the polymer layer) can be obtained by, for example, scanning the surface of the sample within a predetermined range, acquiring force curves at a plurality of points within the predetermined range, calculating the elastic modulus from the force curves, and calculating the average value thereof.
The type of glass constituting the glass substrate is not particularly limited, and examples thereof include soda lime glass, alkali-free glass, borosilicate glass (SiO 2-B2O3 -ZnO-based glass, siO 2-B2O3-Bi2O3 -based glass, etc.), potassium glass, crystallized glass (PbO-containing glass, for example, siO 2 -PbO-based glass, siO 2-PbO-B2O3 -based glass, siO 2-B2O3 -PbO-based glass, etc.), titanium glass, barium glass, boron glass (B 2O3 -ZnO-PbO-based glass, B 2O3-ZnO-Bi2O3 -based glass, B 2O3-Bi2O3 -based glass, B 2O3 -ZnO-based glass, etc.), strontium glass, aluminosilicate glass, sodium zinc glass, sodium barium glass (BaO-SiO 2 -based glass, etc.), and the like. These glasses may be used alone or in combination of 2 or more kinds.
The thickness of the glass substrate is not particularly limited, but is preferably 100 μm or more and 5000 μm or less, more preferably 500 μm or more and 3000 μm or less, as the average thickness. The average thickness was measured for 10 arbitrary sites by using a micrometer, and the average value of the measured values was obtained.
As the polymer constituting the polymer layer, a known polymer can be suitably used.
Examples of the polymer include homopolymers of 1 monomer and copolymers of 2 or more monomers. The above polymers may be used alone or in combination of 2 or more. Among the above polymers, a polymer having hydrophilicity (hydrophilic polymer) is preferable.
The polymer may be produced by a known method, and for example, a solution of a monomer constituting the polymer may be used, and the monomer may be polymerized and synthesized by a known method. The solvent of the monomer solution is not particularly limited, and for example, a solvent described later can be used. Among them, toluene and methanol are preferable.
Examples of the hydrophilic polymer include homopolymers and copolymers of 1 or2 or more hydrophilic monomers, and copolymers of 1 or2 or more hydrophilic monomers and 1 or2 or more other monomers. These may be used alone or in combination of 2 or more.
The hydrophilic monomer is not particularly limited, and various monomers having a hydrophilic group can be used, for example. Examples of the hydrophilic group include known hydrophilic groups such as an amide group, a sulfate group, a sulfonate group, a carboxylate group, a hydroxyl group, an amino group, and an oxyethylene group.
Specific examples of the hydrophilic monomer include (meth) acrylic acid, (meth) acrylic acid esters (e.g., alkoxyalkyl (meth) acrylate such as methoxyethyl (meth) acrylate, (hydroxyalkyl (meth) acrylate such as hydroxyethyl (meth) acrylate), (meth) acrylamide, and (meth) acrylamide derivatives having a cyclic group (e.g., (meth) acryloylmorpholine). Among them, preferred are (meth) acrylic acid, (meth) acrylic acid esters, more preferred are alkoxyalkyl (meth) acrylates, and particularly preferred is 2-methoxyethyl acrylate. These may be used alone or in combination of 2 or more.
The other monomer may be appropriately selected within a range that does not interfere with the effect of the hydrophilic polymer. Specific examples of the other monomer include aromatic monomers such as styrene, vinyl acetate, and N-isopropylacrylamide which can impart temperature responsiveness. These may be used alone or in combination of 2 or more.
Specific examples of the homopolymers and copolymers include homopolymers made of 1 hydrophilic monomer such as polyacrylic acid, polyacrylate, polymethacrylic acid, polymethacrylate, polyacrylmorpholine, polymethacrylylmorpholine, polyacrylamide, polymethacrylamide, polyalkoxyalkylacrylate, polyalkoxyalkylmethacrylate, and the like; copolymers composed of 2 or more hydrophilic monomers exemplified above; copolymers composed of the above-exemplified 1 or more hydrophilic monomers and the above-exemplified 1 or more other monomers; etc. The hydrophilic polymer may be used in an amount of 1 or 2 or more.
Specific examples of the homopolymers and copolymers of the hydrophilic monomers include polyacrylic acid, polyacrylate, polymethacrylic acid, polymethacrylate, polyacrylmorpholine, polymethacrylylmorpholine, polyacrylamide, polymethacrylamide, polyalkoxyalkylacrylate, polyalkoxyalkylmethacrylate, and the like.
Among them, the hydrophilic polymer is preferably a polymer represented by the following formula (I). These may be used alone or in combination of 2 or more.
[ Chemical formula 1]
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. p represents 1 to 8, m represents 1 to 5, and n represents the number of repeating units. )
As the polymer represented by the above formula (I), for example, a polymer represented by the following formula (I-1) can be suitably used. These may be used alone or in combination of 2 or more.
[ Chemical formula 2]
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. m represents 1 to 5, and n represents the number of repeating units. )
The number of carbon atoms of the alkyl group of R 52 is preferably 1 to 10, more preferably 1 to 5. Among them, R 52 is particularly preferably methyl or ethyl. p is preferably 1 to 5, more preferably 1 to 3.m is preferably 1 to 3.n (the number of repeating units) is preferably 15 to 1500, more preferably 40 to 1200.
As the hydrophilic polymer, a copolymer of a compound represented by the following formula (II) and other monomers can also be suitably used. These may be used alone or in combination of 2 or more.
[ Chemical 3]
(Wherein R 51、R52, p, m are as defined above.)
As the compound represented by the above formula (II), for example, a compound represented by the following formula (II-1) can be suitably used. These may be used alone or in combination of 2 or more.
[ Chemical formula 4]
(Wherein R 51、R52 and m are as defined above.)
Among the above hydrophilic polymers, the hydrophilic polymer represented by the above formula (I) is preferable, and the hydrophilic polymer represented by the above formula (I-1) is particularly preferable from the viewpoint of obtaining more excellent effects.
The number average molecular weight (Mn) of the polymer is preferably 8000 to 150000, more preferably 10000 to 60000, and even more preferably 10000 to 39000, from the viewpoint of obtaining more excellent effects. When the polymer is a hydrophilic polymer, the same number average molecular weight (Mn) is also preferable.
In the present specification, the number average molecular weight (Mn) and the weight average molecular weight (Mw) can be obtained by converting standard polystyrene into measured values obtained by Gel Permeation Chromatography (GPC) (GPC-8000 series manufactured by Tosoh Co., ltd., detector: differential refractometer, column chromatography: TSKGEL SUPERMALTPORE HZ-M manufactured by Tosoh Co., ltd.).
The thickness of the polymer layer (layer formed of a polymer) is preferably 10 to 1000nm, more preferably 30 to 700nm, and even more preferably 50 to 350nm. By adjusting the amount within the above range, a favorable low adsorptivity to proteins and cells and a favorable selective capturing property to cancer cells can be expected.
In addition, when the polymer layer is a hydrophilic polymer layer (layer formed of a hydrophilic polymer), the same thickness (film thickness) is also expected.
The thickness of the polymer layer may be measured by a Transmission Electron Microscope (TEM).
At least a part (part or all) of the surface of the polymer layer (the surface of the polymer layer in the polymer-coated glass substrate) has a contact angle with water of preferably 60 degrees or less, more preferably 50 degrees or less. The contact angle of water is preferably 25 degrees or more, more preferably 33 degrees or more.
The polymer layer may be obtained by (1) a method of injecting a polymer solution/dispersion in which a polymer is dissolved/dispersed in various solvents into a surface of a glass substrate (substrate recess or the like), holding the solution for a predetermined period of time, and drying the solution; (2) A method of applying (spraying) the polymer solution/dispersion to the surface of a glass substrate and optionally drying the same; and the like, to produce a polymer-coated glass substrate in which a polymer layer is formed on all or a part of the surface of the glass substrate. Then, by adding other members to the polymer coated glass substrate as necessary, a device capable of capturing, culturing, inspecting, and the like of a specific cell can be manufactured.
The solvent, injection method, coating (spraying) method, etc. may use conventionally known materials and methods.
(1) The holding time and the drying time of (2) may be appropriately set according to the size of the substrate, the kind of the introduced liquid, and the like. The holding time is preferably 10 seconds to 10 hours, more preferably 1 minute to 5 hours, and still more preferably 5 minutes to 2 hours. The drying is preferably carried out at room temperature (about 23 ℃) to 80 ℃, more preferably at room temperature to 60 ℃. In addition, drying under reduced pressure is also possible. After the holding for a predetermined period of time, the excess polymer solution/dispersion may be appropriately discharged and dried.
The solvent is not particularly limited as long as it is a solvent capable of dissolving the polymer, and may be appropriately selected according to the polymer used. Examples of the organic solvent include alcohols such as methanol, ethanol, n-propanol, isopropanol, and methoxypropanol; ketones such as acetone and methyl ethyl ketone; tetrahydrofuran, acetonitrile, ethyl acetate, toluene, and the like.
The concentration of the polymer solution/dispersion is not particularly limited, and may be appropriately selected in consideration of injectability, coatability, sprayability, productivity, and the like, and the concentration of the polymer in the polymer solution/dispersion (100 mass%) is preferably 0.1 to 10.0 mass%, more preferably 0.2 to 5.0 mass%.
The polymer coated glass substrate prepared by the method has the elastic modulus of the surface of the polymer layer in water or aqueous solution below 1.20MPa and soft surface. Therefore, the polymer-coated glass substrate has low trapping ability for normal cells such as blood cells, and has high trapping ability for specific cells such as cancer cells and excellent selective trapping ability for specific cells.
[ Example ]
Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.
Example 1]
(Production of Polymer)
2-Methoxyethyl acrylate (2.5 wt% toluene) was thermally polymerized at 60℃for 7 hours using AIBN (azobisisobutyronitrile) 12.5mg/ml toluene solution to produce poly (2-methoxyethyl acrylate) (PMEA).
145 Μl of 0.155% methanol solution of PMEA was injected into a 2-well chamber slide (manufactured by soda lime glass, average thickness 1300 μm). Then, immediately, the polymer-coated glass substrate was vacuum-dried (coated) in an oven at 40℃for 5 minutes, to produce a polymer-coated glass substrate.
Example 2]
(Production of Polymer)
2-Methoxyethyl acrylate (2.5 wt% methanol) was thermally polymerized at 60℃for 7 hours using AIBN (azobisisobutyronitrile) 12.5mg/ml methanol solution to produce poly (2-methoxyethyl acrylate) (PMEA).
145 Μl of 0.155% methanol solution of PMEA was injected into a 2-well chamber slide (manufactured by soda lime glass, average thickness 1300 μm). Then, immediately, the polymer-coated glass substrate was vacuum-dried (coated) in an oven at 40℃for 5 minutes, to produce a polymer-coated glass substrate.
Comparative example 1]
(Production of Polymer)
2-Methoxyethyl acrylate (5.0 wt% methanol) was thermally polymerized at 60℃for 7 hours using AIBN (azobisisobutyronitrile) 12.5mg/ml methanol solution to produce poly (2-methoxyethyl acrylate) (PMEA).
145 Μl of 0.155% methanol solution of PMEA was injected into a 2-well chamber slide (manufactured by soda lime glass, average thickness 1300 μm). Then, immediately, the polymer-coated glass substrate was vacuum-dried (coated) in an oven at 40℃for 5 minutes, to produce a polymer-coated glass substrate.
For the polymer-coated glass substrates produced in the above examples and comparative examples, the thickness of the polymer layer and the elastic modulus of AFM in PBS (phosphoric acid buffered aqueous solution) were measured by the following methods. The results are shown in Table 1.
[ Thickness of Polymer layer ]
The thickness (film thickness) of the polymer layer formed on the polymer-coated glass substrate was measured by TEM under conditions of an acceleration voltage of 200kV (manufactured by JEOL Co., ltd., JEM-2800). The film thicknesses of examples 1, 2 and comparative example 1 were 78nm, 88nm and 90nm, respectively.
(Determination of elastic modulus in PBS (phosphate buffered saline) by AFM)
The surface of the polymer layer of the polymer-coated glass substrate was dropped with phosphate-buffered saline to form droplets (convex meniscus), and the elastic modulus was measured by the following method using the following Apparatus (AFM). The obtained elastic modulus was defined as the elastic modulus measured in water or an aqueous solution.
In addition, when the elastic modulus was measured, analysis based on JKR contact theory was performed based on the obtained force curve, and the elastic modulus was obtained.
< Method for measuring elastic modulus >
Device (AFM): oxford Instruments manufacture of MFP-3D-SA
Measurement mode: AFM force curve drawing (Force curve mapping)
Cantilever arm: material quality: si, front end radius of curvature R=150 nm, spring constant 0.67N/m
Measurement range: 20 μm by 20 μm scan, elastic modulus was calculated by the two-point JKR method
Scanning speed: 1Hz
Measuring atmosphere: in PBS
Measuring temperature: 23 DEG C
[ Table 1]
The elastic modulus of comparative example 1 was 2MPa or more, and it was considered that the adhesiveness of specific cells such as cancer cells was lowered. In addition, the adhesion of white blood cells is considered to be high.
In contrast, in example 2, the elastic modulus was 0.50MPa or less, and it was considered that the adhesiveness of specific cells such as cancer cells was improved. In addition, the adhesion of leukocytes is thought to be reduced.
In example 1, since the elastic modulus is 0.30MPa or less, it is considered that the adhesiveness of specific cells such as cancer cells is improved as compared with example 2. In addition, the adhesiveness of the white blood cells was considered to be lower than that of example 2.
The invention (1) is a polymer-coated glass substrate, a polymer layer is formed on the surface of the glass substrate,
The elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
The invention (2) is the polymer-coated glass substrate according to the invention (1), wherein the elastic modulus is 0.50MPa or less.
The invention (3) is the polymer-coated glass substrate according to the invention (1), wherein the elastic modulus is 0.30MPa or less.
The invention (4) is the polymer-coated glass substrate according to any one of the combinations of the invention (1) to (3), wherein the elastic modulus is 0.05MPa or more.
The invention (5) is the polymer-coated glass substrate according to any one of the combinations of the invention (1) to (4), wherein the polymer layer is formed of a polymer represented by the following formula (I).
[ Chemical 5]
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. p represents 1 to 8, m represents 1 to 5, and n represents the number of repeating units. )
The invention (6) is the polymer-coated glass substrate according to any one of the combinations of the invention (1) to (4), wherein the polymer layer is formed of a polymer represented by the following formula (I-1).
[ 6] A method for producing a polypeptide
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. m represents 1 to 5, and n represents the number of repeating units. )
The invention (7) is the polymer-coated glass substrate according to any one of the combinations of any one of the inventions (1) to (4), wherein the polymer layer is formed of a copolymer of a compound represented by the following formula (II) with other monomers.
[ Chemical 7]
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. p represents 1 to 8, and m represents 1 to 5. )
The invention (8) is the polymer-coated glass substrate according to any one of the combinations of the invention (1) to (4), wherein the polymer layer is formed of a copolymer of a compound represented by the following formula (II-1) with other monomers.
[ Chemical formula 8]
( Wherein R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. m represents 1 to 5. )
The invention (9) is the polymer-coated glass substrate according to any one of the combinations of the invention (5) to (8), wherein the polymer forming the polymer layer has a number average molecular weight (Mn) of 10000 to 39000.
The invention (10) is a polymer-coated glass substrate according to any combination of the invention (1) to (9), wherein the thickness of the polymer layer is 10 to 1000nm.
The invention (11) is a polymer-coated glass substrate according to any combination of the invention (1) to (10), wherein the elastic modulus is a value measured using an atomic force microscope.
Claims (11)
1. A polymer-coated glass substrate, wherein a polymer layer is formed on the surface of the glass substrate,
The elastic modulus of the surface of the polymer layer in water or an aqueous solution is 1.20MPa or less.
2. The polymer-coated glass substrate of claim 1, wherein the elastic modulus is 0.50MPa or less.
3. The polymer-coated glass substrate of claim 1, wherein the elastic modulus is 0.30MPa or less.
4. The polymer-coated glass substrate of claim 1, wherein the elastic modulus is 0.05MPa or greater.
5. The polymer-coated glass substrate of claim 1, wherein the polymer layer is formed from a polymer of formula (I),
Wherein R 51 represents a hydrogen atom or a methyl group, R 52 represents an alkyl group, p represents 1 to 8, m represents 1 to 5, and n represents the number of repeating units.
6. The polymer-coated glass substrate according to claim 1, wherein the polymer layer is formed of a polymer represented by the following formula (I-1),
Wherein R 51 represents a hydrogen atom or a methyl group, R 52 represents an alkyl group, m represents 1 to 5, and n represents the number of repeating units.
7. The polymer-coated glass substrate according to claim 1, wherein the polymer layer is formed of a copolymer of a compound represented by the following formula (II) with other monomers,
Wherein R 51 represents a hydrogen atom or a methyl group, R 52 represents an alkyl group, p represents 1 to 8, and m represents 1 to 5.
8. The polymer-coated glass substrate according to claim 1, wherein the polymer layer is formed of a copolymer of a compound represented by the following formula (II-1) with other monomers,
Wherein R 51 represents a hydrogen atom or a methyl group, R 52 represents an alkyl group, and m represents 1 to 5.
9. The polymer-coated glass substrate of claim 5, wherein the polymer forming the polymer layer has a number average molecular weight Mn of 10000-39000.
10. The polymer-coated glass substrate of claim 1, wherein the polymer layer has a thickness of 10-1000 nm.
11. The polymer coated glass substrate of claim 1, wherein the elastic modulus is a value determined using an atomic force microscope.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022-206606 | 2022-12-23 | ||
| JP2023182573A JP2024091434A (en) | 2022-12-23 | 2023-10-24 | Polymer-coated glass substrates |
| JP2023-182573 | 2023-10-24 |
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| Publication Number | Publication Date |
|---|---|
| CN118240437A true CN118240437A (en) | 2024-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311480702.XA Pending CN118240437A (en) | 2022-12-23 | 2023-11-08 | Polymer coated glass substrate |
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| Country | Link |
|---|---|
| CN (1) | CN118240437A (en) |
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