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1. 发明授权

US06632641B1 Method and apparatus for performing large numbers of reactions using array assembly with releasable primers 失效
标题翻译：使用具有可释放引物的阵列组合进行大量反应的方法和装置
公开(公告)号：US06632641B1
公开(公告)日：2003-10-14
申请号：US09686597
申请日：2000-10-10
申请人： Thomas M. Brennan , Francois Chatelain , Mark Berninger
发明人： Thomas M. Brennan , Francois Chatelain , Mark Berninger
IPC分类号： C12Q168
CPC分类号： C12Q1/686 , B01J2219/00527 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00635 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00722 , C12Q1/6837 , C12Q2600/156 , C40B40/06 , C12Q2565/518 , C12Q2537/143 , C12Q2565/515 , C12Q2535/125
摘要： The present invention relates to a method and apparatus for performing a large number of reactions using array assembly. In particular, the present invention features a method and apparatus for performing a large number of chemical and biological reactions by bringing two arrays into close apposition and allowing reactants on the surfaces of two arrays to come into contact. The present invention is exemplified by performing a large number of polynucleotide amplification reactions using array assembly. In addition, the present invention features a method and apparatus for coupling the amplification of polynucleotides and the detection of sequence variations, expression levels, and functions thereof.
摘要翻译：本发明涉及使用阵列组合进行大量反应的方法和装置。特别地，本发明的特征在于通过使两个阵列紧密结合并使两个阵列的表面上的反应物接触来进行大量化学和生物反应的方法和装置。通过使用阵列组合进行大量的多核苷酸扩增反应来举例说明本发明。此外，本发明的特征在于用于偶联多核苷酸的扩增的方法和装置以及序列变异，表达水平和功能的检测。

2. 发明授权

US06337393B1 Method and composition for chemical synthesis on an open environment support surface using high boiling point organic solvents to control evaporation 失效
标题翻译：使用高沸点有机溶剂控制蒸发的开放环境支撑表面上化学合成的方法和组成
公开(公告)号：US06337393B1
公开(公告)日：2002-01-08
申请号：US09662066
申请日：2000-09-14
申请人： Thomas M. Brennan , Albrecht W. Frauendorf
发明人： Thomas M. Brennan , Albrecht W. Frauendorf
IPC分类号： C07H2100
CPC分类号： C07H21/00 , B01J19/0046 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00617 , B01J2219/00619 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00675 , B01J2219/00722 , B82Y30/00 , C40B40/06 , C40B50/14 , C40B60/14 , Y10S435/81
摘要： A method for reducing evaporation of a liquid reagent solution during solid phase, micro-scale chemical synthesis of a molecule comprising sub-units on an open environment solid support surface. The method includes the steps of providing an open solid support surface including at least one binding site which is functionalized with a reactive chemical moiety; and depositing a substantially controlled and minute volume of liquid reagent solution onto the support surface, and in contact with the binding site. The reagent solution includes reactants contained in at least one relatively high boiling point solvent, in contrast to standard organic solvents for such reagents. Application of a high boiling point solvent substantially reduces evaporation of the reagent solution in the open environment during synthesis on the solid support while enabling the maintenance of a substantially high reaction yield.
摘要翻译：一种在固相中减少液体试剂溶液的蒸发的方法，包括在开放环境固体支持体表面上的亚单元的分子的微量化学合成。该方法包括以下步骤：提供开放的固体支持物表面，其包括至少一个用反应性化学部分官能化的结合位点; 并将基本受控和微小体积的液体试剂溶液沉积在支撑表面上，并与结合部位接触。与用于这种试剂的标准有机溶剂相反，试剂溶液包括含在至少一个相对高沸点溶剂中的反应物。在固体支持物的合成过程中，高沸点溶剂的应用显着减少了开放环境中试剂溶液的蒸发，同时能够维持基本上高的反应产率。

3. 发明授权

US06210894B1 Method and apparatus for conducting an array of chemical reactions on a support surface 失效
标题翻译：用于在支撑表面上进行化学反应阵列的方法和装置
公开(公告)号：US06210894B1
公开(公告)日：2001-04-03
申请号：US09314456
申请日：1999-05-18
申请人： Thomas M. Brennan
发明人： Thomas M. Brennan
IPC分类号： C12Q168
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/00378 , B01J2219/00432 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00635 , B01J2219/00637 , B01J2219/00639 , B01J2219/00659 , B01J2219/00675 , B01J2219/00711 , B01J2219/00722 , B01J2219/00725 , C03C17/30 , C07B61/00 , C07B2200/11 , C07H21/00 , C07K1/045 , C12Q1/6837 , C12Q1/6874 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14 , C40B80/00 , Y02P20/582
摘要： The invention provides apparatus and methods for making arrays of functionalized binding sites on a support surface. The invention further provides apparatus and methods for sequencing oligonucleotides and for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.
摘要翻译：本发明提供了在支撑表面上制备功能化结合位点阵列的装置和方法。本发明还提供了用于测序寡核苷酸并通过将生物活性大分子特异性结合到肽或肽模拟物的阵列来识别与生物活性大分子结合的肽的氨基酸序列的装置和方法。

4. 发明授权

US5472672A Apparatus and method for polymer synthesis using arrays 失效
标题翻译：使用阵列进行聚合物合成的装置和方法
公开(公告)号：US5472672A
公开(公告)日：1995-12-05
申请号：US142593
申请日：1993-10-22
申请人： Thomas M. Brennan
发明人： Thomas M. Brennan
IPC分类号： C12M1/00 , B01J19/00 , C07B61/00 , C07H21/00 , C07H21/02 , C07H21/04 , C07K1/02 , C07K1/04 , C08F2/00 , C08F2/04 , C08G85/00 , C12N15/09 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14 , G01N35/10
CPC分类号： C07H21/00 , B01J19/0046 , C07K1/04 , C07K1/045 , G01N35/1072 , B01J2219/00286 , B01J2219/0031 , B01J2219/00313 , B01J2219/00315 , B01J2219/00328 , B01J2219/00364 , B01J2219/00369 , B01J2219/00414 , B01J2219/00416 , B01J2219/00418 , B01J2219/00423 , B01J2219/00454 , B01J2219/00459 , B01J2219/005 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00686 , B01J2219/00689 , B01J2219/00695 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , C07B2200/11 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14
摘要： A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24) , and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31) , downstream from the nozzles (22) , sweeps the common chamber ( 31 ) of toxic fumes emitted by the reagents. Each reaction well (26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.
摘要翻译：一种用于构建聚合物链的聚合物合成设备（20），其包括具有喷嘴阵列（22）的头组件（21），每个喷嘴连接到液体试剂（24）的容器（23），以及基座组件）具有反应孔阵列（26）。输送机构（27）对准反应孔（26）和选定的喷嘴（22），用于将液体试剂（24）沉积到选定的反应孔（26）中。滑动密封件（30）定位在头部组件（21）和基座组件（25）之间，以形成在其中包围反应井（26）和喷嘴（22）的公共腔室（31）。从喷嘴（22）的上游进入公共室（31）的气体入口（70）和在公共室（31）之外的喷嘴（22）的下游的气体出口（71）扫过公共室（31）试剂发出的有毒烟雾。每个反应井（26）包括延伸到井（26）中的孔（74），其具有尺寸和尺寸以形成毛细管液体密封，以将试剂溶液（76）保持在井（26）中用于聚合物链增长其中。提供压力调节装置（82），用于控制施加在反应井（26）上的第一气体压力和施加在孔口出口（80）上的第二气体压力之间的压力差，使得在压差超过预定量的试剂溶液（76）通过孔口（74）从孔26排出。也包括在合成装置（20）中合成聚合物链的方法。

5. 发明授权

US5048038A Ion-implanted planar-buried-heterostructure diode laser 失效
标题翻译：离子注入平面埋置异质结二极管激光器
公开(公告)号：US5048038A
公开(公告)日：1991-09-10
申请号：US469996
申请日：1990-01-25
申请人： Thomas M. Brennan , Burrell E. Hammons , David R. Myers , Gregory A. Vawter
发明人： Thomas M. Brennan , Burrell E. Hammons , David R. Myers , Gregory A. Vawter
IPC分类号： H01S5/20 , H01S5/227 , H01S5/32 , H01S5/34
CPC分类号： B82Y20/00 , H01S5/20 , H01S5/227 , H01S5/2059 , H01S5/2275 , H01S5/3211 , H01S5/3215 , H01S5/3409 , H01S5/3428
摘要： A Planar-Buried-Heterostructure, Graded-Index, Separate-Confinement-Heterostructure semiconductor diode laser 10 includes a single quantum well or multi-quantum well active stripe 12 disposed between a p-type compositionally graded Group III-V cladding layer 14 and an n-type compositionally graded Group III-V cladding layer 16. The laser 10 includes an ion implanted n-type region 28 within the p-type cladding layer 14 and further includes an ion implanted p-type region 26 within the n-type cladding layer 16. The ion implanted regions are disposed for defining a lateral extent of the active stripe.
摘要翻译：平面埋置异质结构，分级折射率，分离限制 - 异质结半导体二极管激光器10包括设置在p型组成梯度III-V族包层14和第二组III-V包层14之间的单量子阱或多量子阱有源条纹12。 n型成分分级的III-V族包层16.激光器10包括在p型包层14内的离子注入的n型区域28，并且在n型包层内还包括离子注入的p型区域26 离子注入区域被设置用于限定活性条纹的横向范围。

6. 发明授权

US5003059A Determining DNA sequences by mass spectrometry 失效
标题翻译：通过质谱法测定DNA序列
公开(公告)号：US5003059A
公开(公告)日：1991-03-26
申请号：US209247
申请日：1988-06-20
申请人： Thomas M. Brennan
发明人： Thomas M. Brennan
IPC分类号： G01N27/62 , C07H21/00 , C12Q1/68 , G01N33/60
CPC分类号： C12Q1/6872 , C07H21/00
摘要： This invention relates to the methods, apparatus, reagents and mixtures of reagents for sequencing natural or recombinant DNA and other polynucleotides. In particular, this invention relates to a method for sequencing polynucleotides based on mass spectrometry to determine which of the four bases (adenine, guanine, cytosine or thymine) is a component of the terminal nucleotide. In particular, the present invention relates to identifying the individual nucleotides by the mass of stable nuclide markers contained within either the dideoxynucleotides, the DNA primer, or the deoxynucleotide added to the primer. This invention is particularly useful in identifying specific DNA sequences in very small quantities in biological products produced by fermentation or other genetic engineering techniques. The invention is therefore useful in evaluating safety and other health concerns related to the presence of DNA in products resulting from genetic engineering techniques.
摘要翻译：本发明涉及用于测序天然或重组DNA和其他多核苷酸的试剂的方法，装置，试剂和混合物。特别地，本发明涉及基于质谱法测定多核苷酸的方法，以确定四个碱基（腺嘌呤，鸟嘌呤，胞嘧啶或胸腺嘧啶）中的哪一个是末端核苷酸的组分。特别地，本发明涉及通过添加到引物中的双脱氧核苷酸，DNA引物或脱氧核苷酸中所含的稳定核素标记的质量鉴定单个核苷酸。本发明特别可用于鉴定通过发酵或其他遗传工程技术生产的生物产品中非常少的特定DNA序列。因此，本发明可用于评估与遗传工程技术产生的产品中DNA存在相关的安全性和其他健康问题。

7. 发明授权

US4804782A Branched amides of L-aspartyl-D-amino acid dipeptides 失效
公开(公告)号：US4804782A
公开(公告)日：1989-02-14
申请号：US796173
申请日：1985-11-08
申请人： Thomas M. Brennan , Michael E. Hendrick
发明人： Thomas M. Brennan , Michael E. Hendrick
IPC分类号： A23L27/30 , C07C45/00 , C07C45/29 , C07C45/61 , C07C45/63 , C07C45/64 , C07C45/68 , C07C45/75 , C07C233/00 , C07C323/25 , C07D307/22 , C07D307/32 , C07D331/04 , C07D333/32 , C07D333/36 , C07D335/02 , C07K5/072 , C07C103/37 , A23L1/236 , C07C103/52
CPC分类号： C07D307/32 , A23L27/32 , C07C323/00 , C07C323/25 , C07C45/004 , C07C45/292 , C07C45/61 , C07C45/63 , C07C45/64 , C07C45/68 , C07C45/75 , C07D307/22 , C07D331/04 , C07D333/32 , C07D333/36 , C07D335/02 , C07K5/06113
摘要： Amides of L-aspartyl-D-amino acid dipeptides of the formula ##STR1## and physiologically acceptable cationic and acid addition salts thereof wherein R.sup.a is methyl, ethyl, n-propyl or isopropyl; R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, ##STR2## where at least one of R.sup.3, R.sup.4, R.sup.5, R.sup.6 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms, X is O, S, SO, SO.sub.2, C.dbd.O or CHOH; m is zero or 1-4, n and p are each zero, 1, 2 or 3 where the sum of n+p is not greater than 3 and the sum of the carbon atoms in R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is not greater than six, and when both of R.sup.3 and R.sup.4 or R.sup.5 and R.sup.6 are alkyl they are methyl or ethyl, ##STR3## where one of R.sup.7, R.sup.8, R.sup.9 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms and the sum of the carbon atoms in R.sup.7, R.sup.8 and R.sup.9 is not greater than six, m and q are the same or different and each have the values previously defined for m; ##STR4## where each of R.sup.12 and R.sup.13 are methyl or ethyl, or R.sup.12 is hydrogen and R.sup.13 is alkyl having from one to four carbon atoms, Z is O or NH and t is 1 or 2, ##STR5## where w is 1-4, R.sup.14 and R.sup.16 are each alkyl having from one to four carbon atoms, R.sup.15 is H, OH, methyl or ethyl and the sum of the carbon atoms in R.sup.14, R.sup.15 and R.sup.16 is not greater than six and when both of R.sup.14 and R.sup.15 are alkyl they are methyl or ethyl, and where R.sup.17 and R.sup.19 are alkyl having from one to four carbon atoms, R.sup.18 and R.sup.20 are H or alkyl having one to two carbon atoms, A is OH and B is H, OH or CH.sub.3 and taken together A and B are ##STR6## where the sum of the carbon atoms in R.sup.17, R.sup.18, R.sup.19 and R.sup.20 is not greater than six and when both of R.sup.17 and R.sup.18 or R.sup.19 and R.sup.20 are alkyl they are methyl or ethyl;said amides are potent sweetners having advantages over the prior art, edible compositions containing them, methods for their use in edible compositions and novel amine and amide intermediates useful in their production.

8. 发明授权

US4289704A Preparation of gamma-pyrones 失效
标题翻译： γ-吡喃酮的制备
公开(公告)号：US4289704A
公开(公告)日：1981-09-15
申请号：US164514
申请日：1980-07-02
申请人： Thomas M. Brennan , Daniel P. Brannegan , Paul D. Weeks , Donald E. Kuhla
发明人： Thomas M. Brennan , Daniel P. Brannegan , Paul D. Weeks , Donald E. Kuhla
IPC分类号： C07D309/32 , C07D309/40 , C07D309/22
CPC分类号： C07D309/40 , C07D309/32
摘要： 2-Methyl-3-hydroxy-4H-pyran-4-one is prepared by contacting 1(2-furyl)-1-ethanol in aqueous solution with two equivalents of a halogen oxidant at room temperature and then heating until the hydrolysis of the formed 4-halo-dihydropyran intermediate is substantially complete. Other valuable related gamma-pyrones are prepared in analogous manner from appropriate alcohols.
摘要翻译： 2-甲基-3-羟基-4H-吡喃-4-酮通过在室温下将1（2-呋喃基）-1-乙醇与2当量卤素氧化剂在室温下接触，然后加热至水解形成的4-卤代 - 二氢吡喃中间体基本上完成。其他有价值的有关的γ-吡喃虫是以适当的醇类似的方式制备的。

9. 发明授权

US4076978A Fiber optic bundle beam expander with image intensifier 失效
标题翻译：具有图像增强器的光纤束束扩展器
公开(公告)号：US4076978A
公开(公告)日：1978-02-28
申请号：US732347
申请日：1976-10-14
申请人： Thomas M. Brennan , Robert M. Burley
发明人： Thomas M. Brennan , Robert M. Burley
IPC分类号： G02B6/06 , G02B23/08 , H01J29/89 , H01J31/50 , G02B5/16
CPC分类号： H01J29/892 , G02B23/08 , G02B6/06
摘要： A tapered or twisted fiber optic bundle having a unidirectional diffuser at an output face thereof defines a fiber optic bundle beam expander. In a viewing system, such a beam expander is provided at the output of an image intensifier tube for unidirectionally spreading rays of an amplified image in a horizontal direction for biocular viewing.
摘要翻译：在其输出面具有单向扩散器的锥形或扭曲光纤束限定了光纤束束扩展器。在观察系统中，这种光束扩展器设置在图像增强管的输出处，用于在水平方向上单向扩散放大图像的光线，用于生物观察。

10. 发明授权

US08084245B2 Apparatus and method for polymer synthesis using arrays 失效
标题翻译：使用阵列进行聚合物合成的装置和方法
公开(公告)号：US08084245B2
公开(公告)日：2011-12-27
申请号：US12950335
申请日：2010-11-19
申请人： Thomas M. Brennan
发明人： Thomas M. Brennan
IPC分类号： C12M1/00 , B01L3/02
CPC分类号： C07H21/00 , B01J19/0046 , B01J2219/00286 , B01J2219/0031 , B01J2219/00313 , B01J2219/00315 , B01J2219/00328 , B01J2219/00364 , B01J2219/00369 , B01J2219/00414 , B01J2219/00416 , B01J2219/00418 , B01J2219/00423 , B01J2219/00454 , B01J2219/00459 , B01J2219/005 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00686 , B01J2219/00689 , B01J2219/00695 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , C07B2200/11 , C07K1/04 , C07K1/045 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14 , G01N35/1072
摘要： A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31), downstream from the nozzles (22), sweeps the common chamber (31) of toxic fumes emitted by the reagents. Each reaction well (26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.
摘要翻译：一种用于构建聚合物链的聚合物合成设备（20），其包括具有喷嘴阵列（22）的头组件（21），每个喷嘴连接到液体试剂（24）的容器（23），以及基座组件）具有反应孔阵列（26）。输送机构（27）对准反应孔（26）和选定的喷嘴（22），用于将液体试剂（24）沉积到选定的反应孔（26）中。滑动密封件（30）定位在头部组件（21）和基座组件（25）之间，以形成在其中包围反应井（26）和喷嘴（22）的公共腔室（31）。从喷嘴（22）的上游进入公共室（31）的气体入口（70）和在公共室（31）之外的喷嘴（22）的下游的气体出口（71）扫过公共室（31）试剂发出的有毒烟雾。每个反应井（26）包括延伸到井（26）中的孔（74），其具有尺寸和尺寸以形成毛细管液体密封，以将试剂溶液（76）保持在井（26）中用于聚合物链增长其中。提供压力调节装置（82），用于控制施加在反应井（26）上的第一气体压力和施加在孔口出口（80）上的第二气体压力之间的压力差，使得在压差超过预定量的试剂溶液（76）通过孔口（74）从孔26排出。也包括在合成装置（20）中合成聚合物链的方法。

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