Deep ultraviolet photolithographically defined ultra-thin films for selective cell adhesion and outgrowth and method of manufacturing the same and devices containing the same
AssigneesGeo-Centers, Inc., The United States of America as represented by the Secretary of the Navy
InventorsJacque H. Georger, Jr., David A. Stenger, Thomas L. Fare
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Abstract
Patterned surfaces for the selective adhesion and outgrowth of cells are useful in cell culture devices, prosthetic implants, and cell-based microsensors. Such surfaces may be prepared by a deep ultraviolet photolithographic technique.
Claims20
A patterned surface for the selective adhesion and outgrowth of cells, comprising a patterned ultra-thin film wherein said ultra-thin film contains at least a first portion which has an exposed surface of a cell adhesion promoter and at least a second portion having an exposed surface of a cell adhesion inhibitor, wherein said cell adhesion promoter contains a group selected from the group consisting of --NHCH.sub.2 CH.sub.2 NHCH.sub.2 CH.sub.2 NH.sub.2, --NHCH.sub.2 CH.sub.2 NH.sub.2, 11-aminoundecyl, 3-aminopropyl, 3-(-aminopropoxy)-3,3-dimethyl-1-propenyl, 6-(aminohexyl)propyl, N-(2-aminoethyl)-3-aminopropyl, --(CH.sub.2).sub.3 --NH--(CH.sub.2).sub.2 --NH--(CH.sub.2).sub.3, Gly-Arg-Gly-Asp-Tyr-, and Gly-Tyr-Ile-Gly-Ser-Arg-Tyr, and wherein said cell adhesion inhibitor contains a fluorinated alkyl group.
A patterned surfce for the selective adhesion and outgrowth of cells, comprising a patterned ultra-thin film wherein said ultra-thin film contains at least a first portion which has an exposed surface of a cell adhesion promoter and at least a second portion having an exposed surface of a cell adhesion inhibitor, wherein said patterned surface is prepared by a method comprising:
- (i) coating a substrate with a compound to obtain an ultra-thin film which is reactive to radition and has an exposed surface of at least one cell adhesion promoter or cell adhesion inhibitor;
- (ii) irradiating said ultra-thin film in a patternwise fashion to obtain an irradiated film with a surface region in which at least a fraction of said cell adhesion promoter or cell adhesion inhibitor has been removed;
- and
- (iii) treating said irradiated film with a second compound to bind to said surface region in which at least a fraction of said cell adhesion promoter or said cell adhesion inhibitor has been removed;
- wherein said first compound is
- (a) cell adhesion promoter compound selected from the group consisting of trimethoxysilane N-(2-aminoethyl-3-aminopropyl) trimethoxysilane, 11-aminoundecytrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldimethylethoxysilane, 3-(1-aminopropoxy)-3,3-dimethyl-1-propenyltrimethoxysilane, 6-(aminohexylaminopropyl)trimethoxysilane, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, bis[3-(trimethoxysilyl)propyl]ethylenediamine, trimethoxysilylpropyldiethylenetriamine, (aminoethylaminomethyl)phenethyltrimethoxysilane, isopropyltri-(n-ethylenediamino)ethyltitanate, neopentyl(diallyl)oxytri(n-ethylenediamino)ethyltitanate, neopentyl(diallyl)oxytri(amino)phenyltitanate, neopentyl(diallyl)oxytri(n-ethylenediamino)ethylzirconate, and neopentyl(diallyl)oxytri(m-amino)phenylzirconate;
- (b) a cell adhesion inhibitor compound selected from the group consisting of tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-dimethylchlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-trichlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-methyldichlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-triethoxysilane, (3,3,3-trifluoropropyl)trichlorosilane, (3,3,3-triflurorpropyl)methyldichlorosilane, (3,3,3-triflurorpropyl)-dimethylchlorosilane, (3,3,3-trifluoropropyl)methyldimethoxysilane, (3,3,3-trifluoropropyl)trimethoxysilane, (heptafluoroisopropoxy) propylmethyldichlorosilane, and (3-pentafluorophenylpropyl) dimethylchlorosilane;
- and
- wherein when said first compound is a cell adhesion promoter, said second compound is a cell adhesion inhibitor;
- and wherein when said first compound is a cell adhesion inhibitor, said second compound is a cell adhesion promoter.
A cell culture apparatus, having a patterned surface for the selective adhesion and outgrowth of cells, comprising a patterned ultra-thin film wherein said ultra-thin film contains at least a first portion which has an exposed surface of a cell adhesion promoter and at least a second portion having an exposed surface of a cell adhesion inhibitor, wherein said patterned surface is prepared by a method, comprising:
- (i) coating a substrate with a compound to obtain an ultra-thin film which is reactive to radiation and has an exposed surface of at least one cell adhesion promoter or cell adhesion inhibitor;
- (ii) irradiating said ultra-thin film in a patternwise fashion to obtain an irradiated film with a surface region in which at least a fraction of said cell adhesion promoter or cell adhesion inhibitor has been removed;
- and
- (iii) treating said irradiated film with a second compound to bind to said surface region in which at least a fraction of said cell adhesion promoter or said cell adhesion inhibitor has been removed:
- wherein said first compound is
- (a) cell adhesion promoter compound selected from the group consisting of trimethoxysilane N-(2-aminoethyl-3-aminopropyl) trimethoxysilane, 11-aminoundecyltrimethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropylmethyldiethoxysilane, 3-aminopropyldimethylethoxysilane, 3-(1-aminopropoxy)-3,3-dimethyl-1-propenyltrimethoxysilane, 6-(aminohexylaminopropyl)trimethoxysilane, N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane, bis[3-(trimethoxysilyl)propyl]ethylenediamine, trimethoxysilylpropyldiethylenetriamine, (aminoethylaminomethyl)phenethyltrimethoxysilane, isopropyltri-(n-ethylenediamino)ethyltitanate, neopentyl(diallyl)oxytri(n-ethylenediamino)ethyltitanate, neopentyl(diallyl)oxytri(amino)phenyltitanate, neopentyl(diallyl)oxytri(n-ethylenediamino)ethylzirconate, and neopentyl(diallyl)oxytri(m-amino)phenylzirconate;
- (b) a cell adhesion inhibitor compound selected from the group consisting of tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-dimethylchlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-trichlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-methyldichlorosilane, tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-triethoxysilane, (3,3,3-trifluoropropyl)trichlorosilane, (3,3,3-trifluoropropyl)methyldichlorosilane, (3,3,3-trifluoropropyl)-dimethylchlorosilane, (3,3,3-trifluoropropyl)methyldimethoxysilane, (3,3,3-trifluoropropyl)trimethoxysilane, (heptafluoroisopropoxy) propylmethyldichlorosilane, and (3-pentafluorophenylpropyl) dimethylchlorosilane;
- and
- wherein when said first compound is a cell adhesion promoter, said second compound is a cell adhesion inhibitor;
- and wherein when said first compound is a cell adhesion inhibitor, said second compound is a cell adhesion promoter.
A cell-based microsensor, comprising:
- (i) at least one transducer;
- and
- (ii) a substrate having a patterned surface for the selective adhesion and outgrowth of cells;
- wherein said patterned surface contains at least one region having an exposed surface of at least one cell adhesion promoter, such that said region is spatially related to said transducer so that a cell adhering to said region may be stimulated or detected by said transducer;
- wherein said cell adhesion promoter contains a terminal group selected from the group consisting of --NHCH.sub.2 CH.sub.2 NHCH.sub.2 CH.sub.2 NH.sub.2, --NHCH.sub.2 CH.sub.2 NH.sub.2, 11-aminoundecyl, 3-aminopropyl, 3-(1-aminopropoxy)-3,3-dimethyl-1-propenyl, 6-(aminohexyl)propyl, N-(2-aminoethyl)-3-aminopropyl, --(CH.sub.2).sub.3 --NH-- (CH.sub.2).sub.3 --NH-- (CH.sub.2).sub.3, Gly-Arg-Gly-Asp- Tyr-, and Gly-Tyr-Ile-Gly-Ser-Arg-Tyr.
Dependencies are inferred from the claim text.