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51. 发明申请

US20080176211A1 Microfabricated Cell Sorter 审中-公开
标题翻译：微型细胞分选机
公开(公告)号：US20080176211A1
公开(公告)日：2008-07-24
申请号：US11744097
申请日：2007-05-03
申请人： Charles F. Spence , Anne Y. Fu , Stephen R. Quake , Frances H. Arnold
发明人： Charles F. Spence , Anne Y. Fu , Stephen R. Quake , Frances H. Arnold
IPC分类号： C12Q3/00 , B01J19/00 , B01D57/02 , B01J19/08 , G01N27/26
CPC分类号： G01N27/26 , B01L3/502761 , B01L2200/0647 , B01L2300/0864 , B01L2300/123 , B01L2400/0406 , B01L2400/0415 , B01L2400/0418 , B01L2400/0421 , B01L2400/0424 , B01L2400/0454 , B01L2400/0481 , B01L2400/0487 , B01L2400/0655 , G01N15/14 , G01N2015/149
摘要： The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time. The cells can be sorted into an appropriate branch channel based on the presence or amount of a detectable signal such as an optical signal, with or without stimulation, such as exposure to light in order to promote fluorescence.
摘要翻译：本发明提供了一种用于基于所需特征分选细胞的微制造装置，例如，报道分子标记的细胞可以通过细胞上报告物的存在或水平进行分选。该装置包括具有基板的芯片，微基板将至少一个分析单元微加工。每个分析单元包括主通道，具有通常在一端的样品入口通道和沿其长度的一部分的检测区域。相邻和下游的检测区域，主通道具有通向至少两个分支通道的识别区域或分支点。分析单元还可以根据需要进一步包括额外的入口通道，检测点，分支点和分支通道。包含细胞的流通过检测区域，使得平均一个细胞在给定时间占据检测区域。基于可检测信号（例如光信号）的存在或量，可以将细胞分类到适当的分支通道中，具有或不具有刺激，例如暴露于光以促进荧光。

52. 发明授权

US06540895B1 Microfabricated cell sorter for chemical and biological materials 有权
标题翻译：用于化学和生物材料的微型细胞分选仪
公开(公告)号：US06540895B1
公开(公告)日：2003-04-01
申请号：US09325667
申请日：1999-05-21
申请人： Charles F. Spence , Anne Y. Fu , Stephen R. Quake , Frances H. Arnold
发明人： Charles F. Spence , Anne Y. Fu , Stephen R. Quake , Frances H. Arnold
IPC分类号： G01N2726
CPC分类号： G01N15/14 , B01L3/502707 , B01L3/502738 , B01L3/502761 , B01L2200/0647 , B01L2200/0652 , B01L2300/0654 , B01L2300/0816 , B01L2300/0864 , B01L2300/123 , B01L2400/0406 , B01L2400/0415 , B01L2400/0418 , B01L2400/0421 , B01L2400/0424 , B01L2400/0454 , B01L2400/0481 , B01L2400/0484 , B01L2400/0487 , B01L2400/0655 , G01N2015/149
摘要： The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time. The cells can be sorted into an appropriate branch channel based on the presence or amount of a detectable signal such as an optical signal, with or without stimulation, such as exposure to light in order to promote fluorescence.
摘要翻译：本发明提供了一种用于基于所需特征分选细胞的微制造装置，例如，报道分子标记的细胞可以通过细胞上报告物的存在或水平进行分选。该装置包括具有基板的芯片，微基板将至少一个分析单元微加工。每个分析单元包括主通道，具有通常在一端的样品入口通道和沿其长度的一部分的检测区域。相邻和下游的检测区域，主通道具有通向至少两个分支通道的识别区域或分支点。分析单元还可以根据需要进一步包括额外的入口通道，检测点，分支点和分支通道。包含细胞的流通过检测区域，使得平均一个细胞在给定时间占据检测区域。基于可检测信号（例如光信号）的存在或量，可以将细胞分类到适当的分支通道中，具有或不具有刺激，例如暴露于光以促进荧光。

53. 发明授权

US06524837B1 Hydantoinase variants with improved properties and their use for the production of amino acids 有权
标题翻译：具有改进性质的乙内酰脲酶变体及其用于生产氨基酸的用途
公开(公告)号：US06524837B1
公开(公告)日：2003-02-25
申请号：US09497585
申请日：2000-02-03
申请人： Frances H. Arnold , Oliver May , Karlheinz Drauz , Andreas Bommarius
发明人： Frances H. Arnold , Oliver May , Karlheinz Drauz , Andreas Bommarius
IPC分类号： C12N986
CPC分类号： C12P13/12 , C07H21/04 , C12N9/86 , C12P13/04 , C12P13/06 , C12P13/08 , C12P41/009
摘要： Hydantoinase enzymes which are mutants of a previously isolated hydantoinase having the amino acid SEQ. ID. NO. 2. The mutants include amino acid substitutions at positions 95, 154, 180, 251 and/or 255 of the wild type hydantoinase (SEQ. ID. NO. 2). The mutant hydantoinases, like the parent hydantoinase, are used in the production of optically pure amino acids.
摘要翻译：乙内酰脲酶，其是具有氨基酸SEQ ID NO：1的先前分离的乙内酰脲酶的突变体。 ID。没有。突变体包括野生型乙内酰脲酶（SEQ ID NO：2）的95,54,180,251和/或255位的氨基酸取代。突变的乙内酰脲酶，如亲水乙内酰脲酶，用于生产光学纯氨基酸。

54. 发明授权

US6153410A Recombination of polynucleotide sequences using random or defined primers 失效
标题翻译：使用随机或定义的引物重组多核苷酸序列
公开(公告)号：US6153410A
公开(公告)日：2000-11-28
申请号：US905359
申请日：1997-08-04
申请人： Frances H. Arnold , Zhixin Shao , Joseph A. Affholter , Huimin H Zhao , Lorraine J. Giver
发明人： Frances H. Arnold , Zhixin Shao , Joseph A. Affholter , Huimin H Zhao , Lorraine J. Giver
IPC分类号： C12N15/09 , C12N9/16 , C12N9/56 , C12N9/80 , C12N15/10 , C12Q1/68 , C12P19/34
CPC分类号： C12N15/1027 , C12N9/16 , C12N9/54 , C12N9/80 , C12Q1/6811 , C12Q1/683
摘要： A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.
摘要翻译：公开了一种基于聚合酶催化的引物寡核苷酸延伸的多核苷酸序列的体外诱变和重组方法。该方法包括用随机序列或定义序列引物引发模板多核苷酸以产生具有低水平点突变的短DNA片段池。将DNA片段进行变性，然后退火并进一步进行酶催化的DNA聚合。重复该过程足够次数以产生包含原始模板多核苷酸突变体的全长基因。这些基因可以通过聚合酶链反应进一步扩增，并克隆到用于表达编码蛋白质的载体中。

55. 发明授权

US6063637A Sensors for sugars and other metal binding analytes 失效
标题翻译：糖和其他金属结合分析物的传感器
公开(公告)号：US6063637A
公开(公告)日：2000-05-16
申请号：US875047
申请日：1997-07-07
申请人： Frances H. Arnold , Zhibin Guan , Chao-Tsen Chen , Guohua Chen
发明人： Frances H. Arnold , Zhibin Guan , Chao-Tsen Chen , Guohua Chen
IPC分类号： A61B5/00 , G01N21/00 , G01N21/64 , G01N33/00 , G01N33/14 , G01N33/487
CPC分类号： A61B5/14539 , G01N27/4145 , A61B5/14532 , G01N21/64 , G01N33/143 , Y10T436/142222 , Y10T436/143333 , Y10T436/144444 , Y10T436/20 , Y10T436/200833 , Y10T436/203332
摘要： Sensors (20, 50, 70) for use in detecting the presence of sugars and other analytes (target molecules). The sensor is composed of a metal complex that binds to the target molecule and releases a proton or includes an exchangable ligand which is exchanged for the target molecule during the binding interaction between the metal complex and the target molecule. The result of the binding interaction is the release of a proton, hydroxide ion or ligand species generated during the ligand exchange. Measurement of the release of proton, hydroxide ion or other ligand species from the sensor (20, 50, 70) provides an indirect indication of target molecule concentration. The metal complexes may be attached to support structures (10, 12) to provide both anchoring and positioning of the metal ions to increase selectivity of sugar/metal complex interactions. Detection systems in which pH is used as an indication of proton or hydroxide release are disclosed, as are detection systems in which Cl.sup.- release is used. Methods for monitoring the concentrations of sugars and related molecules using the metal based sensors (20, 50, 70) are also disclosed.
摘要翻译： PCT No.PCT / US97 / 03654 Sec。 371日期1997年7月7日 102（e）日期1997年7月7日PCT 1997年3月3日PCT公布。公开号WO97 / 33177 1997年9月12日发布的传感器（20,50,70）用于检测糖和其他分析物（靶分子）的存在。该传感器由结合目标分子并释放质子的金属络合物组成，或者包括在金属络合物和靶分子之间的结合相互作用期间与靶分子交换的可交换配体。结合相互作用的结果是在配体交换期间产生的质子，氢氧根离子或配体物质的释放。从传感器（20,50,70）释放质子，氢氧根离子或其他配体物质的测量提供了目标分子浓度的间接指示。金属络合物可以连接到支撑结构（10,12），以提供金属离子的锚定和定位，以增加糖/金属络合物相互作用的选择性。公开了使用pH作为质子或氢氧化物释放指示的检测系统，其中使用Cl-释放的检测系统也是如此。还公开了使用金属基传感器（20,50,70）监测糖和相关分子的浓度的方法。

56. 发明授权

US5786428A Adsorbents for amino acid and peptide separation 失效
标题翻译：用于氨基酸和肽分离的吸附剂
公开(公告)号：US5786428A
公开(公告)日：1998-07-28
申请号：US622747
申请日：1996-03-27
申请人： Frances H. Arnold , Vidyasankar Sundaresan
发明人： Frances H. Arnold , Vidyasankar Sundaresan
IPC分类号： B01D15/38 , B01J20/26 , B01J20/32 , C08F12/08 , C08F20/10 , C08F112/08 , C08F212/08
CPC分类号： B01D15/3828 , B01J20/26 , B01J20/268 , B01J20/3204 , B01J20/3208 , B01J20/3219 , B01J20/3265 , B01J20/3278 , B01J20/3282 , B01D15/3833
摘要： An adsorbent which selectively binds to one enantiomer of an optically active amino acid or peptide. The adsorbent includes a polymer matrix which contains one or more metal complexes that are oriented within the polymer matrix by molecular imprinting to provide selective binding of the matrix to only one enantiomer of the optically active amino acid or peptide. Separation systems are disclosed which use the adsorbent as the basis for conducting enantioresolution of optically active amino acids and peptides. Methods for using the adsorbent are also disclosed.
摘要翻译：选择性结合光学活性氨基酸或肽的一个对映异构体的吸附剂。吸附剂包括聚合物基质，其含有通过分子印迹在聚合物基质内取向的一种或多种金属络合物，以提供基质与光学活性氨基酸或肽的仅一个对映异构体的选择性结合。公开了使用吸附剂作为光学活性氨基酸和肽的对映体分析的基础的分离系统。还公开了使用吸附剂的方法。

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