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1.发明授权公开(公告)号：US08288155B2
公开(公告)日：2012-10-16
申请号：US11777919
申请日：2007-07-13
申请人： John R. Havens , Thomas J. Onofrey , Charles H. Greef , Gregory J. Kevorkian , Jain Krotz , Kristie L. Lykstad , Daniel E. Raymond , Howard R. Reese , Regina Rooney , John J. Scott
发明人： John R. Havens , Thomas J. Onofrey , Charles H. Greef , Gregory J. Kevorkian , Jain Krotz , Kristie L. Lykstad , Daniel E. Raymond , Howard R. Reese , Regina Rooney , John J. Scott
CPC分类号： C40B50/14 , B01J19/0046 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00626 , B01J2219/00635 , B01J2219/00637 , B01J2219/00639 , B01J2219/00641 , B01J2219/00653 , B01J2219/00659 , B01J2219/00713 , B01J2219/0072 , C07B2200/11 , C07C319/02 , C07H21/00 , C40B40/06 , G01N33/54353 , G01N33/545 , C07C323/60
摘要： Methods of addressing a biomolecule to a selectively addressable electrode are described. A permeation layer overlying a plurality of selectively addressable electrodes is provided. The permeation layer includes a reactive group that is adapted to bond to a biomolecule and that requires activation through a chemical transformation before bonding to the biomolecule. At least one selectively addressable electrode is biased such that a pH change occurs in an overlying solution of the at least one selectively addressable electrode. The reactive group in a portion of the permeation layer above the at least one selectively addressable electrode is then chemically transformed to an activated reactive group as a result of the pH change. A biomolecule is then bound to the permeation layer overlying the at least one selectively addressable electrode through the activated reactive group.
摘要翻译： 描述了将生物分子寻址到选择性寻址电极的方法。 提供了覆盖多个选择性寻址电极的渗透层。 渗透层包括适于结合生物分子的反应性基团，并且在结合到生物分子之前需要通过化学转化的活化。 至少一个选择性寻址的电极被偏压，使得在所述至少一个选择性寻址电极的上覆溶液中发生pH变化。 作为pH变化的结果，将至少一个可选寻址电极上方的渗透层的一部分中的反应基团化学转化成活化的反应性基团。 然后将生物分子与穿过活化的反应性基团的至少一个选择性寻址电极重叠的渗透层结合。
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2.发明申请公开(公告)号：US20090069198A1
公开(公告)日：2009-03-12
申请号：US11777919
申请日：2007-07-13
申请人： John R. Havens , Thomas J. Onofrey , Charles H. Greef , Gregory J. Kevorkian , Jain Krotz , Kristie L. Lykstad , Daniel E. Raymond , Howard R. Reese , Regina Rooney , John J. Scott
发明人： John R. Havens , Thomas J. Onofrey , Charles H. Greef , Gregory J. Kevorkian , Jain Krotz , Kristie L. Lykstad , Daniel E. Raymond , Howard R. Reese , Regina Rooney , John J. Scott
IPC分类号： C40B50/18
CPC分类号： C40B50/14 , B01J19/0046 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00626 , B01J2219/00635 , B01J2219/00637 , B01J2219/00639 , B01J2219/00641 , B01J2219/00653 , B01J2219/00659 , B01J2219/00713 , B01J2219/0072 , C07B2200/11 , C07C319/02 , C07H21/00 , C40B40/06 , G01N33/54353 , G01N33/545 , C07C323/60
摘要： Methods of addressing a biomolecule to a selectively addressable electrode are described. A permeation layer overlying a plurality of selectively addressable electrodes is provided. The permeation layer includes a reactive group that is adapted to bond to a biomolecule and that requires activation through a chemical transformation before bonding to the biomolecule. At least one selectively addressable electrode is biased such that a pH change occurs in an overlying solution of the at least one selectively addressable electrode. The reactive group in a portion of the permeation layer above the at least one selectively addressable electrode is then chemically transformed to an activated reactive group as a result of the pH change. A biomolecule is then bound to the permeation layer overlying the at least one selectively addressable electrode through the activated reactive group.
摘要翻译： 描述了将生物分子寻址到选择性寻址电极的方法。 提供了覆盖多个选择性寻址电极的渗透层。 渗透层包括适于结合生物分子的反应性基团，并且在结合到生物分子之前需要通过化学转化的活化。 至少一个选择性寻址的电极被偏压，使得在所述至少一个选择性寻址电极的上覆溶液中发生pH变化。 作为pH变化的结果，将至少一个选择性寻址电极上方的渗透层的一部分中的反应基团化学转化成活化的反应性基团。 然后将生物分子与穿过活化的反应性基团的至少一个选择性寻址电极重叠的渗透层结合。
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3.发明授权公开(公告)号：US07270850B2
公开(公告)日：2007-09-18
申请号：US11082325
申请日：2005-03-16
申请人： Jainamma Krotz , Daniel J. Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
发明人： Jainamma Krotz , Daniel J. Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
CPC分类号： C12Q1/002 , B01D67/003 , B01D69/125 , B01D2323/18 , B01D2323/34 , B01D2323/42 , C09D123/26 , C12Q1/003 , G01N33/5438 , G01N33/545
摘要： The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The present invention includes methods for forming a permeation layer on an array of microelectrodes including the steps of attaching a linker to the surface of the array by treating the surface with a linker by vapor deposition and providing a polymerization solution that includes at least one monomer having a polymerizable moiety, a modified streptavidin, a surfactant or porogen, and a cross-linking agent. The surface of the array is then contacted with the polymerization solution and the polymerization solution is then polymerized on the surface of the array to form a permeation layer that is attached o the surface of the array through the linker.
摘要翻译： 本发明提供了用于生物测定的活性电子基质装置上的改进的合成聚合物水凝胶渗透层。 本发明包括在微电极阵列上形成渗透层的方法，包括以下步骤：通过气相沉积用接头处理该表面，并提供包含至少一种具有至少一个单体的聚合溶液，将接头连接到阵列的表面上 可聚合部分，修饰的链霉抗生物素蛋白，表面活性剂或致孔剂和交联剂。 然后将阵列的表面与聚合溶液接触，然后聚合溶液在阵列的表面上聚合，形成通过接头连接在阵列表面上的渗透层。
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公开(公告)号：US07129229B2
公开(公告)日：2006-10-31
申请号：US10344092
申请日：2001-08-10
申请人： Stefan Raddatz , Jochen Müller-Ibeler , Markus Schweitzer , Christoph Brücher , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles H. Greef , Daguang Wang
发明人： Stefan Raddatz , Jochen Müller-Ibeler , Markus Schweitzer , Christoph Brücher , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles H. Greef , Daguang Wang
CPC分类号： A61K31/66 , C07F9/2408 , C07F9/2429
摘要： This invention relates to attachment chemistries for binding macromolecules to a substrate surface or to other conjugation targets. More particularly, this invention relates to attachment chemistries involving branched or linear structures having one or more hydrazide attachment moieties for binding the macromolecules to a substrate surface, or for other conjugation reactions. Novel modifying reagents are provided for the introduction of protected hydrazide attachment moieties or precursor forms of such hydrazides to the macromolecule, either as a single hydrazide or as multiple hydrazides.
摘要翻译： 本发明涉及用于将大分子结合到底物表面或其它共轭靶的附着化学物质。 更具体地说，本发明涉及包含具有一个或多个用于将大分子结合到底物表面或其它共轭反应的一个或多个酰肼连接部分的支链或线性结构的附着化学物质。 提供了新的改性试剂，用于将受保护的酰肼连接部分或这种酰肼的前体形式引入高分子，作为单酰肼或多个酰肼。
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5.发明授权公开(公告)号：US07597932B2
公开(公告)日：2009-10-06
申请号：US11855374
申请日：2007-09-14
申请人： Jainamma Krotz , Daniel Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
发明人： Jainamma Krotz , Daniel Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
CPC分类号： C12Q1/002 , B01D67/003 , B01D69/125 , B01D2323/18 , B01D2323/34 , B01D2323/42 , C09D123/26 , C12Q1/003 , G01N33/5438 , G01N33/545
摘要： The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The present invention includes methods for forming a permeation layer on an array of microelectrodes including the steps of attaching a linker to the surface of the array and providing a polymerization solution that includes a porogen. The surface of the array is then contacted with the polymerization solution and the polymerization solution is then polymerized on the surface of the array to form a permeation layer that is attached o the surface of the array through the linker. The porogen is then removed from the permeation layer, thereby creating void spaces in the permeation layer.
摘要翻译： 本发明提供了用于生物测定的活性电子基质装置上的改进的合成聚合物水凝胶渗透层。 本发明包括在微电极阵列上形成渗透层的方法，包括将接头连接到阵列的表面并提供包含致孔剂的聚合溶液的步骤。 然后将阵列的表面与聚合溶液接触，然后聚合溶液在阵列的表面上聚合，形成通过接头连接在阵列表面上的渗透层。 然后从渗透层除去致孔剂，从而在渗透层中产生空隙。
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6.发明授权公开(公告)号：US06960298B2
公开(公告)日：2005-11-01
申请号：US10014895
申请日：2001-12-10
申请人： Jainamma Krotz , Daniel Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
发明人： Jainamma Krotz , Daniel Smolko , Howard R. Reese , Thomas J. Onofrey , Daguang Wang , Theodore M. Winger , John R. Havens
IPC分类号： G01N33/53 , A61K20060101 , B01D29/00 , B01D39/14 , B01D63/08 , B01J19/00 , C08J5/12 , C12M1/34 , C12Q1/68 , G01N27/26 , G01N27/30 , G01N27/447 , G01N33/543 , G01N33/547 , G01N33/566
CPC分类号： C12Q1/002 , B01D67/003 , B01D69/125 , B01D2323/18 , B01D2323/34 , B01D2323/42 , C09D123/26 , C12Q1/003 , G01N33/5438 , G01N33/545
摘要： 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.
摘要翻译： 本发明提供了用于生物测定的活性电子基质装置上的改进的合成聚合物水凝胶渗透层。 渗透层具有限定的多孔性质，其中介孔的尺寸范围在约100纳米至约1000纳米之间，并且也可以具有微米尺寸范围内的微孔。 与有源电子矩阵器件上的纳米多孔合成水凝胶渗透层相比，介孔合成水凝胶渗透层显示出改进的信号强度和线性特性。 此外，本发明还提供含有用于核酸探针或其他生物分子的共聚附着位点的合成聚合物水凝胶渗透层。
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公开(公告)号：US06306348B1
公开(公告)日：2001-10-23
申请号：US09354931
申请日：1999-07-15
IPC分类号： G01N1500
CPC分类号： B01L3/502761 , B01J19/0046 , B01J19/0093 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01J2219/00853 , B01L3/502707 , B01L3/50273 , B01L3/508 , B01L3/5085 , B01L2200/0647 , B01L2300/0636 , B01L2300/0645 , B01L2300/069 , B01L2400/0415 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C07K1/24 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C13/04 , G11C19/00 , H01L24/95 , H01L25/50 , H01L51/0595 , H01L2924/10253 , H01L2924/14 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： The present invention pertains to a method of, and a device created by, depositing an inorganic permeation layer on a micro-electronic device for molecular biological reactions. The permeation layer is preferably sol-gel. The sol-gel permeation layer can be created with pre-defined porosity, pore size distribution, pore morphology, and surface area. The sol-gel permeation layer may also function as the attachment layer of the micro-electric device.
摘要翻译： 本发明涉及通过在用于分子生物反应的微电子器件上沉积无机渗透层而产生的方法和装置。 渗透层优选为溶胶 - 凝胶。 溶胶 - 凝胶渗透层可以产生具有预定孔隙率，孔径分布，孔形态和表面积。 溶胶 - 凝胶渗透层也可以用作微电子装置的附着层。
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8.发明申请BIOMOLECULES HAVING MULTIPLE ATTACHMENT MOIETIES FOR BINDING TO A SUBSTRATE SURFACE 有权具有多个附着力的生物分子结合到基底表面公开(公告)号：US20110201080A1
公开(公告)日：2011-08-18
申请号：US12946777
申请日：2010-11-15
申请人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
发明人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
CPC分类号： C07H19/04 , C07H21/00 , C12Q1/68 , G01N33/54353
摘要： Compounds relating to attachment chemistries for binding biomolecules to a substrate surface are described. These include compounds of the following structure: The biomolecule includes a single nucleic acid, oligonucleotides, polynucleotides, DNAs, RNAs, proteins, peptides, enzymes, antibodies, CNAs (cyclohexyl nucleic acids), p-MeNAs (methyl or methoxy phosphate nucleic acids), peptide nucleic acids (PNAs), and pyranosyl RNAs (p-RNAs).
摘要翻译： 描述了与用于将生物分子结合到基底表面的附着化学物质有关的化合物。 这些包括以下结构的化合物：生物分子包括单个核酸，寡核苷酸，多核苷酸，DNAs，RNAs，蛋白质，肽，酶，抗体，CNA（环己基核酸），p-MeNA（甲基或甲氧基磷酸核酸） ，肽核酸（PNA）和吡喃糖基RNA（p-RNA）。
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9.发明授权Biomolecules having multiple attachment moieties for binding to a substrate surface 有权具有多个附着部分的生物分子用于结合底物表面公开(公告)号：US07186813B1
公开(公告)日：2007-03-06
申请号：US10181207
申请日：2000-08-11
申请人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
发明人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
CPC分类号： C07H21/00 , A61K47/61 , C07B2200/11 , C07F9/2408 , C07F9/2429 , C07F9/65616 , C40B40/00 , G01N33/54353
摘要： Biomolecules are provided having multiple binding sites for attachment to a substrate surface. The multiple attachment sites may be produced directly on the biomolecule or through use of branched phosphoramidite moieties that can be added in multiple to form dendritic structures which can in turn provide attachment sites for substrate binding moieties. Substrate binding moieties may include noncovalent binding moieties. For covalent binding moieties oligonucleotides containing hydrazides are provided. These hydrazides can be introduced via protected building blocks such as phosphoramidites or via building blocks containing precursor forms of such hydrazides.
摘要翻译： 提供了生物分子，其具有用于附着到基底表面的多个结合位点。 多个附着位点可以直接在生物分子上生产，或通过使用可以多次加入以形成树突状结构的支链亚磷酰胺部分，这又可以提供底物结合部分的附着位点。 底物结合部分可以包括非共价结合部分。 对于共价结合部分，提供了含有酰肼的寡核苷酸。 这些酰肼可以通过保护的结构单元如亚磷酰胺或通过含有这种酰肼前体形式的构建块引入。
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10.发明授权Biomolecules having multiple attachment moieties for binding to a substrate surface 有权具有多个附着部分的生物分子用于结合底物表面公开(公告)号：US08067581B2
公开(公告)日：2011-11-29
申请号：US12946777
申请日：2010-11-15
申请人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
发明人： Markus Schweitzer , Norbert Windhab , John R. Havens , Thomas J. Onofrey , Charles Greef , Daguang Wang
CPC分类号： C07H19/04 , C07H21/00 , C12Q1/68 , G01N33/54353
摘要： Compounds relating to attachment chemistries for binding biomolecules to a substrate surface are described. These include compounds of the following structure: The biomolecule includes a single nucleic acid, oligonucleotides, polynucleotides, DNAs, RNAs, proteins, peptides, enzymes, antibodies, CNAs (cyclohexyl nucleic acids), p-MeNAs (methyl or methoxy phosphate nucleic acids), peptide nucleic acids (PNAs), and pyranosyl RNAs (p-RNAs).
摘要翻译： 描述了与用于将生物分子结合到基底表面的附着化学物质有关的化合物。 这些包括以下结构的化合物：生物分子包括单个核酸，寡核苷酸，多核苷酸，DNAs，RNAs，蛋白质，肽，酶，抗体，CNA（环己基核酸），p-MeNA（甲基或甲氧基磷酸核酸） ，肽核酸（PNA）和吡喃糖基RNA（p-RNA）。
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