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1. 发明公开

EP0717749A1 SELF-ADDRESSABLE SELF-ASSEMBLING MICROELECTRONIC SYSTEMS AND DEVICES FOR MOLECULAR BIOLOGICAL ANALYSIS AND DIAGNOSTICS 失效
标题翻译：自寻址的振作起来TRANSLATED微电子系统和分子生物学TRALYSE和诊断器械
公开(公告)号：EP0717749A1
公开(公告)日：1996-06-26
申请号：EP95925571.0
申请日：1995-07-05
申请人： NANOGEN, INC.
发明人： HELLER, Michael, J. , TU, Eugene , EVANS, Glen, A. , SOSNOWSKI, Ronald, G.
IPC分类号： G01N21 , B01J19 , B01L3 , B82B1 , B82B3 , C07B61 , C07H21 , C07K1 , C12N15 , C12Q1 , G01N27 , G01N33 , G01N37 , G11C13 , G11C19 , H01L21 , H01L29 , H01L51 , H05K1 , C40B40 , C40B60
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.

2. 发明授权

EP1056887B1 METHODS FOR DETERMINATION OF LENGTH POLYMORPHISMS IN DNA 有权
标题翻译：用于确定DNA长度多态性
公开(公告)号：EP1056887B1
公开(公告)日：2006-05-31
申请号：EP99908154.0
申请日：1999-02-12
申请人： NANOGEN, INC.
发明人： SOSNOWSKI, Ronald, G. , TU, Eugene
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/04 , B01J19/00
CPC分类号： H01L29/6656 , B01J2219/00653 , B01J2219/00659 , C12Q1/6825 , C12Q1/6827 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C12Q2565/518 , C12Q2537/125 , C12Q2525/151 , C12Q2565/607
摘要： Methods and apparatus are provided for the analysis and determination of the nature of repeat units in a genetic target. In one method of this invention, the nature of the repeat units in the genetic target is determined by the steps of providing a plurality of hybridization complex assays arrayed on a plurality of test sites, where the hybridization complex assay includes at least a nucleic acid target containing a simple repetitive DNA sequence, a capture probe having a first unique flanking sequence and n repeat units, where n = 0, 1, 2..., or fractions thereof, being complementary to the target sequence, and a reporter probe having a selected sequence complementary to the same target sequence strand wherein the selected sequence of the reporter includes a second unique flanking sequence and m repeat units, where m = 0, 1, 2..., or fractions thereof, but where the sum of repeat units in the capture probe plus reporter probe is greater than 0 (n+m⊃0). In accordance with this method, the sequence of the capture probe differs at least two test sites. The hybridization complex assays are then monitored to determine concordance and discordance among the hybridization complex assays at the test sites as determined at least in part by hybridization stability. Ultimately, the nature of the repeat units in the target sequence may be determined based upon the concordant/discordant determination coupled with knowledge of the probes located in the hybridization complex at that site. In one aspect of this invention, electronic stringency control may be utilized either during the initial hybridization phase, such as to aid in the proper indexing of hybridized materials, or during the concordance/discordance phase, or both. In yet another aspect of this invention, a system includes a plurality of sites wherein each site includes at least a probe having a first unique flanking sequence, a second unique flanking sequence and an intervening repeat unit series having a variable number of repeat units. The existence of loop-outs, or conditions of exact concordance, may be determined. Applications include paternity testing, forensic use, and disease diagnostics, such as for the identification of the existence of a clonal tumor.

3. 发明公开

EP1056887A1 METHODS AND APPARATUS FOR DETERMINATION OF LENGTH POLYMORPHISMS IN DNA 有权
标题翻译：用于确定DNA长度多态性
公开(公告)号：EP1056887A1
公开(公告)日：2000-12-06
申请号：EP99908154.0
申请日：1999-02-12
申请人： NANOGEN, INC.
发明人： SOSNOWSKI, Ronald, G. , TU, Eugene
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/04
CPC分类号： H01L29/6656 , B01J2219/00653 , B01J2219/00659 , C12Q1/6825 , C12Q1/6827 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C12Q2565/518 , C12Q2537/125 , C12Q2525/151 , C12Q2565/607
摘要： Methods and apparatus are provided for the analysis and determination of the nature of repeat units in a genetic target. In one method of this invention, the nature of the repeat units in the genetic target is determined by the steps of providing a plurality of hybridization complex assays arrayed on a plurality of test sites, where the hybridization complex assay includes at least a nucleic acid target containing a simple repetitive DNA sequence, a capture probe having a first unique flanking sequence and n repeat units, where n = 0, 1, 2..., or fractions thereof, being complementary to the target sequence, and a reporter probe having a selected sequence complementary to the same target sequence strand wherein the selected sequence of the reporter includes a second unique flanking sequence and m repeat units, where m = 0, 1, 2..., or fractions thereof, but where the sum of repeat units in the capture probe plus reporter probe is greater than 0 (n+m⊃0). In accordance with this method, the sequence of the capture probe differs at least two test sites. The hybridization complex assays are then monitored to determine concordance and discordance among the hybridization complex assays at the test sites as determined at least in part by hybridization stability. Ultimately, the nature of the repeat units in the target sequence may be determined based upon the concordant/discordant determination coupled with knowledge of the probes located in the hybridization complex at that site. In one aspect of this invention, electronic stringency control may be utilized either during the initial hybridization phase, such as to aid in the proper indexing of hybridized materials, or during the concordance/discordance phase, or both. In yet another aspect of this invention, a system includes a plurality of sites wherein each site includes at least a probe having a first unique flanking sequence, a second unique flanking sequence and an intervening repeat unit series having a variable number of repeat units. The existence of loop-outs, or conditions of exact concordance, may be determined. Applications include paternity testing, forensic use, and disease diagnostics, such as for the identification of the existence of a clonal tumor.

4. 发明授权

EP0717749B1 SELF-ADDRESSABLE SELF-ASSEMBLING MICROELECTRONIC SYSTEMS AND DEVICES FOR MOLECULAR BIOLOGICAL ANALYSIS AND DIAGNOSTICS 失效
标题翻译：自寻址的振作起来TRANSLATED微电子系统和分子生物学TRALYSE和诊断器械
公开(公告)号：EP0717749B1
公开(公告)日：2003-02-12
申请号：EP95925571.2
申请日：1995-07-05
申请人： NANOGEN, INC.
发明人： HELLER, Michael, J. , TU, Eugene , EVANS, Glen, A. , SOSNOWSKI, Ronald, G.
IPC分类号： G01N33/543 , B01J19/00
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.

5. 发明公开

EP1173611A1 METHODS FOR DETERMINATION OF SINGLE NUCLEIC ACID POLYMORPHISMS USING A BIOELECTRONIC MICROCHIP 审中-公开
标题翻译：方法来确定单核苷酸通过使用生物电MICROCHIP
公开(公告)号：EP1173611A1
公开(公告)日：2002-01-23
申请号：EP00918506.7
申请日：2000-03-28
申请人： NANOGEN, INC.
发明人： NERENBERG, Michael, I. , CANTER, David, M. , RADTKEY, Ray, R. , OCONNELL, James, P. , WANG, Ling , SOSNOWSKI, Ronald, G.
IPC分类号： C12Q1/68 , C12P19/34 , A01N1/02 , C07H21/04
CPC分类号： C12Q1/6827 , C12Q2565/501
摘要： Methods are provided for the analysis and determination of the nature of single nucleic acid polymorphisms (SNPs) in a genetic target. In one method of this invention, the nature of the SNPs in the genetic target is determined by the steps of providing a plurality of hybridization complexes arrayed on a plurality of test sites on an electronically bioactive microchip, where the hybridization complex includes at least a nucleic acid target containing an SNP, a stabilizer probe having a sequence complementary to the target sequence and/or reporter probe, and a reporter probe having a selected sequence complementary to either the stabilizer or the same target sequence strand wherein a selected sequence of the reporter includes either a wild type nucleotide or a nucleotide corresponding to the SNP of the target. In accordance with the invention, the stabilizer, reporter and target amplicons are hybridized using electronic assistance of the microchip system such that base-stacking energies are utilized in discerning among other identifying indicators, the presence of wild type or polymorphism sequence. Applications include disease diagnostics, such as for the identification of polymorphisms in structural genes, regulatory regions, antibiotic or chemotherapeutic resistance conferring regions, or for SNPs associated with speciation or used for determination of genetic linkage.

6. 发明公开

EP1036085A1 SELF-ADDRESSABLE SELF-ASSEMBLING MICROELECTRONIC INTEGRATED SYSTEMS, COMPONENT DEVICES, MECHANISMS, METHODS, AND PROCEDURES FOR MOLECULAR BIOLOGICAL ANALYSIS AND DIAGNOSTICS 审中-公开
标题翻译：本身一起寻址TRANSLATED集成微电子系统，部件装置，机构，方法和分析方法分子生物学及规例
公开(公告)号：EP1036085A1
公开(公告)日：2000-09-20
申请号：EP98961847.5
申请日：1998-12-01
申请人： NANOGEN, INC.
发明人： SOSNOWSKI, Ronald, G. , BUTLER, William, F. , TU, Eugene , NERENBERG, Michael, I. , HELLER, Michael, J. , EDMAN, Carl, F.
IPC分类号： C07H21/00
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.

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