IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0014895
(2001-12-10)
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발명자
/ 주소 |
- Krotz, Jainamma
- Smolko, Daniel
- Reese, Howard R.
- Onofrey, Thomas J.
- Wang, Daguang
- Winger, Theodore M.
- Havens, John R.
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출원인 / 주소 |
|
대리인 / 주소 |
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인용정보 |
피인용 횟수 :
22 인용 특허 :
67 |
초록
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The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The permeation layers have a defined porous character, with mesopores in a size range between about 100 nanometers and about 1000 nanometers, and ma
The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The permeation layers have a defined porous character, with mesopores in a size range between about 100 nanometers and about 1000 nanometers, and may also have micropores in the micrometer size range. The mesoporous synthetic hydrogel permeation layers demonstrate improved signal intensity and linearity characteristics as compared to nanoporous synthetic hydrogel permeation layers on active electronic matrix devices. In addition, the present invention also provides synthetic polymer hydrogel permeation layers which contain copolymerized attachment sites for nucleic acid probes or other biomolecules.
대표청구항
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1. A mesoporous synthetic polymer hydrogel permeation layer overlying an electrode on a substrate, wherein the permeation layer comprises mesopores which are between about 100 nm and 1000 nm across, wherein the permeation layer is covalently anchored to the electrode and wherein the electrode compri
1. A mesoporous synthetic polymer hydrogel permeation layer overlying an electrode on a substrate, wherein the permeation layer comprises mesopores which are between about 100 nm and 1000 nm across, wherein the permeation layer is covalently anchored to the electrode and wherein the electrode comprises a silicon-containing conductive material.2. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the mesopores are between about 100 nm and about 500 nm across.3. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the mesopores are between about 200 nm and about 500 nm across.4. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer further comprises micropores which are between about 1.0 μm and 3.0 μm across.5. The mesoporous synthetic polymer hydrogel permeation layer of claim 4 wherein the micropores are between about 1.0 μm and 2.0 μm across.6. The mesoporous synthetic polymer hydrogel permeation layer of claim 4 wherein the micropores are between about 1.0 μm and 1.5 μm across.7. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer is between about 0.5 μm and about 10 μm thick when dry.8. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer is between about 1.0 μm and about 5.0 μm thick when dry.9. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer is between about 1.0 μm and about 2.0 μm thick when dry.10. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the polymer comprises a polymerized acryloyl or acrylamido monomer.11. The mesoporous synthetic polymer hydrogel permeation layer of claim 10 wherein the acryloyl or acrylamido monomer is an acrylamide.12. The mesoporous synthetic polymer hydrogel permeation layer of claim 10 wherein the acryloyl or acrylamido monomer is an N-substituted acrylamide.13. The mesoporous synthetic polymer hydrogel permeation layer of claim 10 wherein the acryloyl or acrylamido monomer is an N-substituted methacrylamide.14. The mesoporous synthetic polymer hydrogel permeation layer of claim 10 wherein the acryloyl or acrylamido monomer is methacrylamide.15. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer is covalently anchored to the electrode.16. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the electrode comprises a material selected from the group consisting of: platinum silicide, titanium silicide, gold silicide, and tungsten silicide.17. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer is covalently anchored to the substrate around the electrode.18. The mesoporous synthetic polymer hydrogel permeation layer of claim 17 wherein the permeation layer is further covalently anchored to the electrode.19. The mesoporous synthetic polymer hydrogel permeation layer of claim 1 wherein the permeation layer comprises a copolymerized attachment moiety for the attachment of specific binding entities.20. The mesoporous synthetic polymer hydrogel permeation layer of claim 19 wherein the specific binding entity is copolymerized with the synthetic polymer hydrogel through a structure of the general formula: wherein, P is a polymerizable moiety covalently attached to one or two moieties selected from the group consisting of: a monomeric unit of the synthetic polymer and another P-X-R group, as defined herein, wherein the other P-X-R group may be the same as or different from the first P-X-R group, further wherein the dashed line is a covalent bond to the second moiety if P is covalently attached to two moieties; X is a covalent bond or a linking moiety; and R is a functional moiety for attaching, either covalently or non-covalently, a biomolecule. 21. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein R is attached to a biomolecule.22. The mesoporous synthetic polymer hydrogel permeation layer of claim 21 wherein the biomolecule is a nucleic acid.23. The mesoporous synthetic polymer hydrogel permeation layer of claim 21 wherein the biomolecule is a protein.24. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein R is selected from the group consisting of biotin, avidin, streptavidin, and another biotin binding moiety.25. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein R is streptavidin.26. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein R is selected from the group consisting of aldehyde, carboxylic acid, acyl halide, succinimidyl, maleimidyl, thiol, hydrazide, hydrazine, amine, ester, thioester, ketal, and disulfide moieties.27. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein P is selected from the group consisting of acrylamide, acrylate, methacrylate, methacrylamide, allyl, amino, and epoxy moieties.28. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein P is an acryloyl or acrylamido moiety.29. The mesoporous synthetic polymer hydrogel permeation layer of claim 20 wherein X is a covalent bond.30. A mesoporous synthetic polymer hydrogel permeation layer overlying an electrode on a substrate, wherein the permeation layer has a θ value between about 2.0 and about 4.0 when compared to a standard permeation layer composition S, wherein said composition comprises a ratio of Acrylamide: Bisacrylamide 19:1 mol/mol, total monomer content 20% by weight, wherein θ is defined by the equation: wherein integrated light intensity readings λ are taken using dark field microscopy on a compound optical microscope of the dry hydrogel permeation layer on the substrate (λ), the standard permeation layer (λs) and a non-phase separated or solid layer (λ0).31. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer has a θ value between about 2.0 and about 3.8 when compared to composition S.32. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer has a θ value between about 2.0 and about 3.0 when compared to composition S.33. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer has a θ value between about 3.0 and about 3.8 when compared to composition S.34. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer is between about 0.5 μm and about 10 μm thick when dry.35. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer is between about 1.0 μm and about 5.0 μm thick when dry.36. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer is between about 1.0 μm and about 2.0 μm thick when dry.37. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the polymer comprises a polymerized acryloyl or acrylamido monomer.38. The mesoporous synthetic polymer hydrogel permeation layer of claim 37 wherein the acryloyl or acrylamido monomer is an acrylamide.39. The mesoporous synthetic polymer hydrogel permeation layer of claim 37 wherein the acryloyl or acrylamido monomer is an N-substituted acrylamide.40. The mesoporous synthetic polymer hydrogel permeation layer of claim 37 wherein the acryloyl or acrylamido monomer is an N-substituted methacrylamide.41. The mesoporous synthetic polymer hydrogel permeation layer of claim 37 wherein the acryloyl or acrylamido monomer is methacrylamide.42. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer is covalently anchored to the electrode.43. The mesoporous synthetic polymer hydrogel permeation layer of claim 42 wherein the electrode comprises a silicon-containing conductive material.44. The mesoporous synthetic polymer hydrogel permeation layer of claim 43 wherein the electrode comprises a material selected from the group consisting of: platinum silicide, titanium silicide, gold silicide, and tungsten silicide.45. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer is covalently anchored to the substrate around the electrode.46. The mesoporous synthetic polymer hydrogel permeation layer of claim 45 wherein the permeation layer is further covalently anchored to the electrode.47. The mesoporous synthetic polymer hydrogel permeation layer of claim 30 wherein the permeation layer comprises a copolymerized attachment moiety for the attachment of specific binding entities.48. The mesoporous synthetic polymer hydrogel permeation layer of claim 47 wherein the specific binding entity is copolymerized with the synthetic polymer hydrogel through a structure of the general formula: wherein, P is a polymerizable moiety covalently attached to one or two moieties selected from the group consisting of: a monomeric unit of the synthetic polymer and another P-X-R group, as defined herein, wherein the other P-X-R group may be the same as or different from the first P-X-R group, further wherein the dashed line is a covalent bond to the second moiety if P is covalently attached to two moieties; X is a covalent bond or a linking moiety; and R is a functional moiety for attaching, either covalently or non-covalently, a biomolecule. 49. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is attached to a biomolecule.50. The mesoporous synthetic polymer hydrogel permeation layer of claim 49 wherein the biomolecule is a nucleic acid.51. The mesoporous synthetic polymer hydrogel permeation layer of claim 49 wherein the biomolecule is a protein.52. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is selected from the group consisting of biotin, avidin, streptavidin, and another biotin binding moiety.53. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is streptavidin.54. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is selected from the group consisting of aldehyde, carboxylic acid, acyl halide, succinimidyl, maleimidyl, thiol, hydrazide, hydrazine, amine, ester, thioester, ketal, and disulfide moieties.55. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is a hydrazide moiety.56. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is a succinimidyl ester moiety.57. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is an aldehyde moiety.58. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein R is a psoralen moiety.59. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein P is selected from the group consisting of acrylamide, acrylate, methacrylate, methacrylamide, allyl, amino, and epoxy moieities.60. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein P is selected an acryloyl or acrylamido moiety.61. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein X is a covalent bond.62. The mesoporous synthetic polymer hydrogel permeation layer of claim 48 wherein X is a polyalkylene glycol linker.63. A mesoporous synthetic polymer hydrogel permeation layer overlying an electrode on a substrate, wherein the permeation layer comprises mesopores which are between about 100 nm and 1000 nm across, wherein the permeation layer comprises a copolymerized attachment moiety for the attachment of specific binding entities, and wherein the specific binding entities are copolymerized with the permeation layer according to a structure of the general formula:wherein,P is a polymerizable moiety covalently attached to one or two moieties selected from the group consisting of: a monomeric unit of the synthetic polymer and another P-X-R group, as defined herein, wherein the other P-X-R group may be the same as or different from the first P-X-R group, further wherein the dashed line is a covalent bond to the second moiety if P is covalently attached to two moieties; X is a covalent bond or a linking moiety; and R is a functional moiety for attaching, either covalently or non-covalently, a biomolecules, wherein R is selected from the group consisting of a hydrazide, succinimidyl ester, aldehyde, and psoralen moiety. 64. The mesoporous synthetic polymer hydrogel permeation layer of claim 63 wherein P is selected from the group consisting of acrylamide, acrylate, methacrylate, methacrylamide, allyl, amino, and epoxy moieties.65. The mesoporous synthetic polymer hydrogel permeation layer of claim 63 wherein P is an acryloyl or acrylamido moiety.66. The mesoporous synthetic polymer hydrogel permeation layer of claim 63 wherein X is a covalent bond.67. The mesoporous synthetic polymer hydrogel permeation layer of claim 63 wherein R is attached to a biomolecule.68. The mesoporous synthetic polymer hydrogel permeation layer of claim 67 wherein the biomolecule is a nucleic acid.69. The mesoporous synthetic polymer hydrogel permeation layer of claim 67 wherein the biomolecule is a protein.70. A mesoporous synthetic polymer hydrogel permeation layer overlying an electrode on a substrate, wherein the permeation layer comprises mesopores which are between about 100 nm and 1000 nm across, wherein the permeation layer comprises a copolymerized attachment moiety for the attachment of specific binding entities, and wherein the specific binding entities are copolymerized with the permeation layer according to a structure of the general formula: wherein,P is a polymerizable moiety covalently attached to one or two moieties selected from the group consisting of: a monomeric unit of the synthetic polymer and another P-X-R group, as defined herein, wherein the other P-X-R group may be the same as or different from the first P-X-R group, further wherein the dashed line is a covalent bond to the second moiety if P is covalently attached to two moieties; X is a polyalkylene glycol linker; and R is a functional moiety for attaching, either covalently or non-covalently, a biomolecules. 71. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein P is selected from the group consisting of acrylamide, acrylate, methacrylate, methacrylamide, allyl, amino, and epoxy moieties.72. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein P is an acryloyl or acrylamido moiety.73. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein X is a covalent bond.74. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein R is attached to a biomolecule.75. The mesoporous synthetic polymer hydrogel permeation layer of claim 74 wherein the biomolecule is a nucleic acid.76. The mesoporous synthetic polymer hydrogel permeation layer of claim 74 wherein the biomolecule is a protein.77. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein R is selected from the group consisting of biotin, avidin, streptavidin, and another biotin binding moiety.78. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein R is streptavidin.79. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein R is selected from the group consisting of aldehyde, carboxylic acid, acyl halide, succinimidyl, maleimidyl, thiol, hydrazide, hydrazine, amine, ester, thioester, ketal, and disulfide moieties.80. The mesoporous synthetic polymer hydrogel permeation layer of claim 70 wherein R is selected from the group consisting of a hydrazide, succinimidyl ester, aldehyde, and psoralen moiety.
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