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公开(公告)号：US06238624B1
公开(公告)日：2001-05-29
申请号：US08726278
申请日：1996-10-04
IPC分类号： G01N1506
CPC分类号： C07K1/04 , B01J19/0046 , B01J19/0093 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01J2219/00822 , B01J2219/00828 , B01J2219/00844 , B01J2219/00853 , B01L3/502707 , B01L3/502715 , B01L3/502761 , B01L3/5085 , B01L2300/0636 , B01L2300/0645 , B01L2300/0816 , B01L2300/0819 , B01L2300/0829 , B01L2300/0877 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L29/7834 , H01L2224/45144 , H01L2224/95144 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/0102 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253 , Y10S435/808 , Y10S435/814 , Y10S436/805 , Y10T436/25125 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
摘要翻译： 设计制造了一种自寻址的自组装微电子器件，主动执行和控制微步形式的多步分子生物反应。 这些反应包括核酸杂交，抗体/抗原反应，诊断和生物聚合物合成。 该器件可以使用微光刻和微加工技术制造。 该设备可以电子控制特定绑定实体到特定微位置的传输和附着。 特异性结合实体包括分子生物学分子，例如核酸和多肽。 该装置随后可以控制分析物或反应物在寻址的特定微位置的转运和反应。 该装置能够浓缩分析物和反应物，去除非特异性结合的分子，为DNA杂交反应提供严格控制，并改善分析物的检测。 该设备可以电子复制。
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2.发明授权Self-addressable self-assembling microelectronic systems and devices for molecular biological analysis and diagnostics 有权用于分子生物学分析和诊断的自寻址自组装微电子系统和器件公开(公告)号：US07947486B2
公开(公告)日：2011-05-24
申请号：US11702353
申请日：2007-02-05
CPC分类号： C07K1/04 , B01J19/0046 , B01J19/0093 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01J2219/00822 , B01J2219/00828 , B01J2219/00844 , B01J2219/00853 , B01L3/502707 , B01L3/502715 , B01L3/502761 , B01L3/5085 , B01L2300/0636 , B01L2300/0645 , B01L2300/0816 , B01L2300/0819 , B01L2300/0829 , B01L2300/0877 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L29/7834 , H01L2224/45144 , H01L2224/95144 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/0102 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253 , Y10S435/808 , Y10S435/814 , Y10S436/805 , Y10T436/25125 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A method for analyzing nucleic acid obtained from a cell sample on a platform is described. A platform having a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence, is provided. The cell selector is contacted with a cell sample, wherein a portion of the cells remain associated with the cell selector. At least a portion of cells associated with the cell selector are lysed to release a nucleic acid sample. The nucleic acid selector is then contacted with the nucleic acid sample, such that a portion of the nucleic acid sample remains associated with the nucleic acid selector. The associated nucleic acid sample is then released from the nucleic acid selector and then is contacted with the array of microlocations, such that at least a portion of the released nucleic acid sample hybridizes with the capture sequence.
摘要翻译： 描述了用于分析从平台上的细胞样品获得的核酸的方法。 提供了具有细胞选择剂，核酸选择剂和微位点阵列的平台，其中至少一个微位置具有相关联的捕获序列。 细胞选择器与细胞样品接触，其中一部分细胞保持与细胞选择器相关联。 将与细胞选择器相关联的至少一部分细胞裂解释放核酸样品。 然后使核酸选择剂与核酸样品接触，使得核酸样品的一部分保留与核酸选择器相关联。 然后将相关核酸样品从核酸选择器中释放，然后与微位点阵列接触，使得至少一部分释放的核酸样品与捕获序列杂交。
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3.发明申请Self-addressable self-assembling microelectronic systems and devices for molecular biological analysis and diagnostics 有权用于分子生物学分析和诊断的自寻址自组装微电子系统和器件公开(公告)号：US20100173792A1
公开(公告)日：2010-07-08
申请号：US11702353
申请日：2007-02-05
IPC分类号： C40B30/04
CPC分类号： C07K1/04 , B01J19/0046 , B01J19/0093 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01J2219/00822 , B01J2219/00828 , B01J2219/00844 , B01J2219/00853 , B01L3/502707 , B01L3/502715 , B01L3/502761 , B01L3/5085 , B01L2300/0636 , B01L2300/0645 , B01L2300/0816 , B01L2300/0819 , B01L2300/0829 , B01L2300/0877 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L29/7834 , H01L2224/45144 , H01L2224/95144 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/0102 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253 , Y10S435/808 , Y10S435/814 , Y10S436/805 , Y10T436/25125 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A method for analyzing nucleic acid obtained from a cell sample on a platform is described. A platform having a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence, is provided. The cell selector is contacted with a cell sample, wherein a portion of the cells remain associated with the cell selector. At least a portion of cells associated with the cell selector are lysed to release a nucleic acid sample. The nucleic acid selector is then contacted with the nucleic acid sample, such that a portion of the nucleic acid sample remains associated with the nucleic acid selector. The associated nucleic acid sample is then released from the nucleic acid selector and then is contacted with the array of microlocations, such that at least a portion of the released nucleic acid sample hybridizes with the capture sequence.
摘要翻译： 描述了用于分析从平台上的细胞样品获得的核酸的方法。 提供了具有细胞选择剂，核酸选择剂和微位点阵列的平台，其中至少一个微位置具有相关联的捕获序列。 细胞选择器与细胞样品接触，其中一部分细胞保持与细胞选择器相关联。 将与细胞选择器相关联的至少一部分细胞裂解释放核酸样品。 然后使核酸选择剂与核酸样品接触，使得核酸样品的一部分保留与核酸选择器相关联。 然后将相关核酸样品从核酸选择器中释放，然后与微位点阵列接触，使得至少一部分释放的核酸样品与捕获序列杂交。
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公开(公告)号：US07172864B1
公开(公告)日：2007-02-06
申请号：US09490965
申请日：2000-01-24
CPC分类号： B01L3/5085 , 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 , B01J2219/00637 , B01J2219/00641 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L3/502707 , B01L2200/0647 , B01L2300/0636 , B01L2300/0645 , B01L2300/0877 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L25/50 , H01L2224/45144 , H01L2224/95145 , H01L2924/10253 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
摘要翻译： 设计制造了一种自寻址的自组装微电子器件，主动执行和控制微步形式的多步分子生物反应。 这些反应包括核酸杂交，抗体/抗原反应，诊断和生物聚合物合成。 该器件可以使用微光刻和微加工技术制造。 该设备可以电子控制特定绑定实体到特定微位置的传输和附着。 特异性结合实体包括分子生物学分子，例如核酸和多肽。 该装置随后可以控制分析物或反应物在寻址的特定微位置的转运和反应。 该装置能够浓缩分析物和反应物，去除非特异性结合的分子，为DNA杂交反应提供严格控制，并改善分析物的检测。 该设备可以电子复制。
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5.发明授权
公开(公告)号：US6051380A
公开(公告)日：2000-04-18
申请号：US986065
申请日：1997-12-05
申请人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
发明人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
IPC分类号： C12N15/09 , B01J19/00 , B01L3/00 , C07B61/00 , C07H21/00 , C07K1/04 , C12Q1/68 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/02 , G11C19/00 , H01L21/336 , H01L21/98 , H01L29/78
CPC分类号： H01L29/7834 , B01J19/0046 , B01J19/0093 , B01L3/502707 , B01L3/50273 , B01L3/502761 , B01L3/5085 , B82Y10/00 , B82Y5/00 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6825 , C12Q1/6832 , C12Q1/6837 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00635 , B01J2219/00637 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L2200/0647 , B01L2200/10 , B01L2300/0636 , B01L2300/0645 , B01L2400/0415 , B01L2400/0421 , C07B2200/11 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/04 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/01025 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253
摘要： A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific microlocations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific microlocations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
摘要翻译： 设计制造了一种自寻址的自组装微电子器件，主动执行和控制微步形式的多步分子生物反应。 这些反应包括核酸杂交，抗体/抗原反应，诊断和生物聚合物合成。 该器件可以使用微光刻和微加工技术制造。 该装置可以电子控制特定结合实体到特定微位置的转运和附着。 特异性结合实体包括分子生物学分子，例如核酸和多肽。 该装置随后可以控制分析物或反应物在所寻址的特定微位置的转运和反应。 该装置能够浓缩分析物和反应物，去除非特异性结合的分子，为DNA杂交反应提供严格控制，并改善分析物的检测。 该设备可以电子复制。
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公开(公告)号：US6048690A
公开(公告)日：2000-04-11
申请号：US855058
申请日：1997-05-14
IPC分类号： B01J19/00 , B01L3/00 , B82B3/00 , C07B61/00 , C07H21/00 , C07K1/04 , C12Q1/68 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , C40B70/00 , G01N33/543 , G02B6/122 , G06N3/00 , G06N3/06 , G06N3/12 , G11B7/0037 , G11B7/0045 , G11B7/005 , G11B7/24 , G11B7/244 , G11C13/02 , G11C13/04 , G11C19/00 , H01L21/336 , H01L21/98 , H01L29/78 , H01L51/00 , H01L51/30
CPC分类号： B01J19/0046 , B01J19/0093 , B01L3/502761 , B01L3/5085 , B82B3/00 , B82Y10/00 , B82Y20/00 , B82Y30/00 , B82Y40/00 , B82Y5/00 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6818 , C12Q1/6837 , G01N33/54366 , G02B6/1225 , G06N3/002 , G06N3/061 , G06N3/123 , G11B7/0037 , G11B7/0045 , G11B7/00455 , G11B7/005 , G11B7/0052 , G11B7/24 , G11B7/244 , G11C13/0014 , G11C13/0019 , G11C13/04 , G11C19/00 , H01L24/95 , H01L25/50 , H01L51/0595 , B01J2219/00315 , B01J2219/00317 , B01J2219/00497 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00545 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/00612 , B01J2219/00621 , B01J2219/0063 , B01J2219/00637 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00707 , B01J2219/00711 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L2200/025 , B01L2200/0663 , B01L2200/12 , B01L2300/0636 , B01L2300/0645 , B01L2400/0421 , C07B2200/11 , C12Q1/683 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , C40B70/00 , H01L2924/01005 , H01L2924/01006 , H01L2924/01011 , H01L2924/01012 , H01L2924/01013 , H01L2924/01019 , H01L2924/01033 , H01L2924/01039 , H01L2924/01047 , H01L2924/01057 , H01L2924/01061 , H01L2924/01063 , H01L2924/01065 , H01L2924/01074 , H01L2924/01075 , H01L2924/01078 , H01L2924/01082 , H01L2924/12042 , H01L51/0093
摘要： Methods for electronic perturbation of fluorescence, chemilluminescence and other emissive materials provide for molecular biological analysis. In a preferred method for hybridization analysis of a sample, an electronic stringency control device is used to perform the steps of: providing the sample, a first probe with a fluorescent label and a second probe with a label under hybridization conditions on the electronic stringency control device, forming a hybridization product, subjecting the hybridization product to an electric field force, monitoring the fluorescence from the hybridization product, and analyzing the fluorescent signal. The label preferably serves as a quencher for the fluorescent label. In yet another aspect of this invention, a method for achieving electronic fluorescence perturbation on an electronic stringency control device comprising the steps of: locating a first polynucleotide and a second polynucleotide adjacent the electronic stringency control device, the first polynucleotide and second polynucleotide being complementary over at least a portion of their lengths and forming a hybridization product, the hybridization product having an associated environmental sensitive emission label, subjecting the hybridization product and label to a varying electrophoretic force, monitoring the emission from the label, and analyzing the monitored emission to determine the electronic fluorescence perturbation effect. In yet another aspect of this invention, a method is provided for electronic perturbation catalysis of substrate molecules on an electronic control device containing at least one microlocation comprising the steps of: immobilizing on the microlocation an arrangement of one or more reactive groups, exposing the reactive groups to a solution containing the substrate molecules of interest, and applying an electronic pulsing sequence which causes charge separation between the reactive groups to produce a catalytic reaction on the substrate molecules.
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7.发明授权公开(公告)号：US06518022B1
公开(公告)日：2003-02-11
申请号：US09444539
申请日：1999-11-22
申请人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
发明人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
IPC分类号： C12Q168
CPC分类号： H01L29/7834 , 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 , B01J2219/00635 , B01J2219/00637 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L3/502707 , B01L3/50273 , B01L3/502761 , B01L3/5085 , B01L2200/0647 , B01L2200/10 , B01L2300/0636 , B01L2300/0645 , B01L2400/0415 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6825 , C12Q1/6832 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C13/04 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/01025 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific microlocations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific microlocations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
摘要翻译： 设计制造了一种自寻址的自组装微电子器件，主动执行和控制微步形式的多步分子生物反应。 这些反应包括核酸杂交，抗体/抗原反应，诊断和生物聚合物合成。 该器件可以使用微光刻和微加工技术制造。 该装置可以电子控制特定结合实体到特定微位置的转运和附着。 特异性结合实体包括分子生物学分子，例如核酸和多肽。 该装置随后可以控制分析物或反应物在所寻址的特定微位置的转运和反应。 该装置能够浓缩分析物和反应物，去除非特异性结合的分子，为DNA杂交反应提供严格控制，并改善分析物的检测。 该设备可以电子复制。
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8.发明授权公开(公告)号：US08114589B2
公开(公告)日：2012-02-14
申请号：US11726520
申请日：2007-03-22
申请人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
发明人： Ronald G. Sosnowski , William F. Butler , Eugene Tu , Michael I. Nerenberg , Michael J. Heller , Carl F. Edman
CPC分类号： H01L29/7834 , 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 , B01J2219/00635 , B01J2219/00637 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L3/502707 , B01L3/50273 , B01L3/502761 , B01L3/5085 , B01L2200/0647 , B01L2200/10 , B01L2300/0636 , B01L2300/0645 , B01L2400/0415 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6825 , C12Q1/6832 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/0014 , G11C13/0019 , G11C13/04 , G11C19/00 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L2224/95145 , H01L2224/95147 , H01L2924/01019 , H01L2924/01025 , H01L2924/01046 , H01L2924/01078 , H01L2924/01079 , H01L2924/10253 , C12Q2565/515 , C12Q2565/607 , H01L2924/00
摘要： A method for electronically stabilizing hybridization of nucleic acids bound at a test site of a microelectronic device is described. First and second negatively charged nucleic acids are provided, the second nucleic acid being bound to the test site. A zwitterionic buffer having a conductance of less than 100 mS/cm is applied to the microelectronic device. A current is applied to the test site to positively bias the test site, such that the first negatively charged nucleic acid is transported to the positively biased test site having the bound the second negatively charged nucleic acid. At the test site, the first and second negatively charged nucleic acids hybridize. The zwitterionic buffer acquires a net positive charge under influence of the current, such that the positively charged zwitterionic buffer stabilizes the hybridization by reducing the repulsion between the first and second negatively charged nucleic acids.
摘要翻译： 描述了用于电子稳定在微电子器件的测试位点处结合的核酸杂交的方法。 提供第一和第二带负电荷的核酸，第二核酸与测试部位结合。 将具有小于100mS / cm 2的电导的两性离子缓冲液施加到微电子器件。 将电流施加到测试部位以使测试部位正偏置，使得将第一带负电荷的核酸转运到具有结合第二带负电荷核酸的正偏压测试位点。 在测试位点，第一和第二带负电荷的核酸杂交。 两性离子缓冲液在电流影响下获得净正电荷，使得带正电的两性离子缓冲液通过降低第一和第二带负电的核酸之间的排斥来稳定杂交。
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公开(公告)号：US08389212B1
公开(公告)日：2013-03-05
申请号：US09358788
申请日：1999-07-22
申请人： Michael J. Heller , Eugene Tu
发明人： Michael J. Heller , Eugene Tu
CPC分类号： B01L3/5085 , B01J19/0046 , B01J19/0093 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01L3/502707 , B01L2300/0636 , B01L2300/0645 , B01L2300/0829 , B01L2300/0877 , B01L2400/0421 , B82Y5/00 , B82Y10/00 , C07B2200/11 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G01N27/3276 , G11C13/0014 , G11C13/0019 , G11C19/00 , H01L24/95 , H01L25/50 , H01L29/6656 , H01L29/6659 , H01L29/66628 , H01L29/7834 , H01L2224/45124 , H01L2224/45144 , H01L2224/95085 , H01L2224/95145 , H01L2924/00014 , H01L2924/09701 , H01L2924/10253 , H01L2924/12033 , H01L2924/12043 , H01L2924/15788 , Y10S435/808 , Y10S435/814 , Y10S436/805 , Y10T436/25125 , C12Q2565/515 , C12Q2565/607 , H01L2924/00 , H01L2224/48
摘要： A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
摘要翻译： 设计制造了一种自寻址的自组装微电子器件，主动执行和控制微步形式的多步分子生物反应。 这些反应包括核酸杂交，抗体/抗原反应，诊断和生物聚合物合成。 该器件可以使用微光刻和微加工技术制造。 该设备可以电子控制特定绑定实体到特定微位置的传输和附着。 特异性结合实体包括分子生物学分子，例如核酸和多肽。 该装置随后可以控制分析物或反应物在寻址的特定微位置的转运和反应。 该装置能够浓缩分析物和反应物，去除非特异性结合的分子，为DNA杂交反应提供严格控制，并改善分析物的检测。 该设备可以电子复制。
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公开(公告)号：US5632957A
公开(公告)日：1997-05-27
申请号：US304657
申请日：1994-09-09
申请人： Michael J. Heller , Eugene Tu , William F. Butler
发明人： Michael J. Heller , Eugene Tu , William F. Butler
IPC分类号： G01N35/00 , B01J19/00 , B01L3/00 , C07B61/00 , C07H21/00 , C07K1/04 , C12M1/00 , C12Q1/68 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G01N33/53 , G01N37/00 , G11C13/02 , G11C19/00 , H01L21/336 , H01L21/98 , H01L29/78 , C12M1/34 , C12M1/42
CPC分类号： G11C13/0019 , B01J19/0046 , B01J19/0093 , B01L3/502761 , B01L3/5085 , B82Y10/00 , B82Y5/00 , C07H21/00 , C07K1/04 , C07K1/045 , C07K1/047 , C12Q1/6813 , C12Q1/6816 , C12Q1/6825 , C12Q1/6837 , G11C13/0014 , G11C19/00 , H01L25/50 , B01J2219/00315 , B01J2219/00317 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00614 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00653 , B01J2219/00659 , B01J2219/00686 , B01J2219/00689 , B01J2219/00713 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B01J2219/00783 , B01J2219/00828 , B01J2219/00853 , B01L2200/025 , B01L2200/143 , B01L2300/0636 , B01L2300/0645 , B01L2300/0816 , B01L2300/0838 , B01L2300/0877 , B01L2400/0421 , B01L3/502707 , B01L3/502715 , C07B2200/11 , C40B40/06 , C40B40/10 , C40B40/12 , C40B60/14 , G11C13/04 , H01L2924/0002 , H01L2924/09701
摘要： A system for performing molecular biological diagnosis, analysis and multi-step and multiplex reactions utilizes a self-addressable, self-assembling microelectronic system for actively carrying out controlled reactions in microscopic formats. These reactions include most molecular biological procedures, such as nucleic acid hybridization, antibody/antigen reaction, and clinical diagnostics. Multi-step combinatorial biopolymer synthesis may be performed. A controller interfaces with a user via input/output devices, preferably including a graphical display. Independent electronic control is achieved for the individual microlocations. In the preferred embodiment, the controller interfaces with a power supply and interface, the interface providing selective connection to the microlocations, polarity reversal, and optionally selective potential or current levels to individual electrodes. A system for performing sample preparation, hybridization and detection and data analysis integrates multiple steps within a combined system. Charged materials are transported preferably via free field electrophoresis. DNA complexity reduction is achieved preferably by binding of DNA to a support, followed by cleaving unbound materials, such as by restriction enzymes, followed by transport of the cleaved DNA fragments. Active, programmable matrix devices are formed in a variety of formats, including a square matrix pattern with fanned out electrical connections, an array having electrical connections and optionally optical connections from beneath the specific microlocations. A highly automated DNA diagnostic system results.
摘要翻译： 用于进行分子生物学诊断，分析和多步骤和多重反应的系统利用自寻址的自组装微电子系统来主动进行微观格式的受控反应。 这些反应包括大多数分子生物学方法，如核酸杂交，抗体/抗原反应和临床诊断。 可以进行多步组合生物聚合物的合成。 控制器通过输入/输出设备与用户接口，优选地包括图形显示器。 对于单个微位置实现独立的电子控制。 在优选实施例中，控制器与电源和接口接口，该接口提供对微位置的选择性连接，极性反转以及对各个电极的任选选择性电位或电流水平。 用于进行样品制备，杂交和检测和数据分析的系统集成了组合系统中的多个步骤。 带电材料优选通过自由电泳进行输送。 DNA复合物的降低优选通过将DNA与载体结合，然后用限制酶切割未结合的材料，然后转移切割的DNA片段来实现。 活动的可编程矩阵器件以各种格式形成，包括具有扇形电连接的方形矩阵图案，具有电连接的阵列和可选地从特定微位置下方的光学连接。 高度自动化的DNA诊断系统结果。
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