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1. 发明申请

WO2008073607A3 A METHOD FOR ESTIMATING ERROR FROM A SMALL NUMBER OF EXPRESSION SAMPLES 审中-公开
标题翻译：一种从少量表达样本中估计错误的方法
公开(公告)号：WO2008073607A3
公开(公告)日：2008-12-11
申请号：PCT/US2007083333
申请日：2007-11-01
申请人： HELICOS BIOSCIENCES CORP , THAYER EDWARD
发明人： THAYER EDWARD
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G06F19/20
摘要： A method for estimating error in expression data. In one embodiment, the method includes single molecule sequencing a plurality of expression tags from an organism; removing expression tags that ambiguously relate to multiple genes; assigning each remaining expression tag to a respective gene; selecting a random subset of the expression tags; and counting the number of expression tags associated with each gene. The process of selecting a random subset of the expression tags; and counting the number of expression tags associated with each gene is repeated a predetermined number of times, both for expression tags sequenced before and after exposure of the organism to a perturbation. The method also includes the step of calculating a measure of error in response to the counts of the number of expression tags before and after the perturbation.
摘要翻译：用于估计表达数据中的误差的方法。在一个实施方案中，该方法包括来自生物体的多个表达标签的单分子测序; 去除与多个基因模糊相关的表达标签; 将每个剩余的表达标签分配给各自的基因; 选择表达标签的随机子集; 并计算与每个基因相关的表达标签的数量。选择表达式标签的随机子集的过程; 并且计数与每个基因相关的表达标签的数目重复预定的次数，这两者用于在生物暴露于微扰之前和之后测序的表达标签。该方法还包括响应于扰动之前和之后的表达标签的数量的计数来计算误差度量的步骤。

2. 发明申请

WO2008039772A3 POLYMERASE VARIANTS FOR DNA SEQUENCING 审中-公开
标题翻译：用于DNA测序的聚合酶变体
公开(公告)号：WO2008039772A3
公开(公告)日：2008-10-30
申请号：PCT/US2007079421
申请日：2007-09-25
申请人： HELICOS BIOSCIENCES CORP , BUZBY PHILIP R
发明人： BUZBY PHILIP R
IPC分类号： C12N9/00 , C07H21/04 , C12P19/34 , C12Q1/68 , G01N33/53
CPC分类号： C12Y207/07007 , C12N9/1252
摘要： Described herein is a mutant polymerase, specifically the Klenow exo- polymerase in which the proline at amino acid position 680 is replaced by a glycine (P680G), and its use in sequencing a single polynucleotide template using single molecule sequencing.
摘要翻译：本文描述了突变型聚合酶，特别是其中氨基酸位置680处的脯氨酸被甘氨酸替代的Klenow外切聚合酶（P680G），以及其在使用单分子测序对单个多核苷酸模板进行测序中的用途。

3. 发明申请

WO2008073890A2 BUFFER COMPOSITION 审中-公开
标题翻译：缓冲剂组合物
公开(公告)号：WO2008073890A2
公开(公告)日：2008-06-19
申请号：PCT/US2007086978
申请日：2007-12-10
申请人： HELICOS BIOSCIENCES CORP , BUZBY PHILIP R
发明人： BUZBY PHILIP R
IPC分类号： C12N9/22 , C12Q1/68
CPC分类号： C12Q1/6848 , C12Q2527/125 , C12Q2521/101
摘要： The invention provides compositions for improving the accuracy of a sequencing-by-synthesis reaction by minimizing the incorporation of unlabeled dNTPs.
摘要翻译：本发明提供了用于通过最小化未标记的dNTPs的掺入来提高合成测序反应的准确度的组合物。

4. 发明申请

WO2008016909A3 NUCLEOTIDE ANALOGS 审中-公开
标题翻译：核素类似物
公开(公告)号：WO2008016909A3
公开(公告)日：2008-03-20
申请号：PCT/US2007074831
申请日：2007-07-31
申请人： HELICOS BIOSCIENCES CORP , SIDDIQI SUHAIB M , KRZYMANSKA-OLEJNIK EDYTA , ORGUEIRA HERMAN ANTONIO , BAI XIAOPENG
发明人： SIDDIQI SUHAIB M , KRZYMANSKA-OLEJNIK EDYTA , ORGUEIRA HERMAN ANTONIO , BAI XIAOPENG
IPC分类号： C07H19/06 , C07H19/16 , C07H21/00 , C07H21/02 , C07H21/04 , C12P19/38 , C12Q1/68
CPC分类号： C07H21/00 , C07H19/00 , C07H19/06 , C07H19/16 , C07H21/02 , C07H21/04
摘要： The invention provides nucleotides of Formula (I) for use in sequencing nucleic acid molecules. Formula (I) wherein, B is selected from the group consisting of a purine, a pyrimidine, and analogs thereof, R 1 is selected from the group consisting of OH and -O-blocking agent, R 2 is selected from the group consisting of H and OH, R 3 is selected from the group consisting of Formula (A) and Formula (B), R 4 is selected from the group consisting of alkyl, O, S, and NR 5 , R 5 is selected from the group consisting of H and alkyl, R 6 is N 3 , R 7 is an alkyl linker, L is a label, m, at each occurrence, independently is an integer from 1 to 3, n, at each occurrence, independently is an integer from 1 to 18, and p, at each occurrence, independently is an integer from 0 to 11.
摘要翻译：本发明提供用于测序核酸分子的式（I）核苷酸。式（I）其中B选自嘌呤，嘧啶及其类似物，R 1选自OH和-O-封闭剂，R 1， SUP> 2 选自H和OH，R 3选自式（A）和式（B），R 4， / SUP>选自烷基，O，S和NR 5，R 5选自H和烷基，R SUP > 6是N 3，R 7是烷基连接基，L是每次出现时的标记m，独立地是1至3的整数在每次出现时，n独立地为1〜18的整数，p在每次出现时独立地为0〜11的整数。

5. 发明申请

WO2007062160A8 METHODS AND COMPOSITIONS FOR SEQUENCING A NUCLEIC ACID 审中-公开
标题翻译：用于测序核酸的方法和组合物
公开(公告)号：WO2007062160A8
公开(公告)日：2008-02-14
申请号：PCT/US2006045276
申请日：2006-11-22
申请人： HELICOS BIOSCIENCES CORP , SIDDIQI SUHAIB M , BUZBY PHILIP R , AFEYAN NOUBAR B , LIU DAVID R
发明人： SIDDIQI SUHAIB M , BUZBY PHILIP R , AFEYAN NOUBAR B , LIU DAVID R
IPC分类号： C07H21/00 , C12Q1/68
CPC分类号： C07H21/00 , C12Q1/6869 , C12Q2533/101 , C12Q2525/117 , C12Q2523/107
摘要： The invention provides a family of nucleotide analogs useful in sequencing nucleic acids containing a homopolymer region comprising, for example, two or more base repeats, and to sequencing methods using such nucleotide analogs.
摘要翻译：本发明提供了可用于测序含有例如两个或多个碱基重复序列的均聚物区域的核酸的核苷酸类似物家族，以及使用此类核苷酸类似物的测序方法。

6. 发明申请

WO2006007207A3 METHODS AND DEVICES FOR NUCLEIC ACID SEQUENCE DETERMINATION 审中-公开
标题翻译：用于核酸序列测定的方法和装置
公开(公告)号：WO2006007207A3
公开(公告)日：2007-02-22
申请号：PCT/US2005018602
申请日：2005-05-25
申请人： HELICOS BIOSCIENCES CORP , HARRIS TIMOTHY , BUZBY PHILIP RICHARD , JAROSZ MIRNA , DIMEO JAMES JOSEPH , GILL JAMIE
发明人： HARRIS TIMOTHY , BUZBY PHILIP RICHARD , JAROSZ MIRNA , DIMEO JAMES JOSEPH , GILL JAMIE
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , B01J19/0046 , B01J2219/00432 , B01J2219/00436 , B01J2219/00497 , B01J2219/005 , B01J2219/00511 , B01J2219/00527 , B01J2219/00574 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/00628 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00675 , B01J2219/00677 , B01J2219/00689 , B01J2219/00707 , B01J2219/00722 , B82Y30/00 , C12Q1/6837 , C12Q1/6874 , C12Q2549/125
摘要： Methods of the invention comprise methods and devices for nucleic acid sequence determination. Generally, the invention relates to preparing a substrate for sequencing a target nucleic acid.
摘要翻译：本发明的方法包括用于核酸序列测定的方法和装置。通常，本发明涉及制备用于测序靶核酸的底物。

7. 发明申请

WO2006055521A9 TIRF SINGLE MOLECULE ANALYSIS AND METHOD OF SEQUENCING NUCLEIC ACIDS 审中-公开
标题翻译： TIRF单分子分析和序列核酸分析方法
公开(公告)号：WO2006055521A9
公开(公告)日：2006-08-17
申请号：PCT/US2005041264
申请日：2005-11-15
申请人： HELICOS BIOSCIENCES CORP , HARRIS TIMOTHY D , BUZBY PHILIP R , JAROSZ MIRNA , GILL JAIME , WEISS HOWARD , LAPIDUS STANLEY N
发明人： HARRIS TIMOTHY D , BUZBY PHILIP R , JAROSZ MIRNA , GILL JAIME , WEISS HOWARD , LAPIDUS STANLEY N
IPC分类号： G01N21/64 , C12Q1/68
CPC分类号： G01N21/648 , C12Q1/6869 , G01N21/6458 , G01N2021/6419 , G02B2207/113 , C12Q2565/102 , C12Q2563/107 , C12Q2523/313
摘要： An apparatus for analyzing the presence of a single molecule comprises a sample plate (30') having a sample located thereon. In one embodiment the apparatus comprises two lasers (46', 46'') for providing illumination light at two different wavelengths suitable for exciting fluorescence in the sample, a collimator comprising a band-pass filter (50', 55''), a diverging lens (54', 54''), a field stop (62'), and a converging lens (66') for directing the illunination light through a total internal reflection objective (74') onto the sample, and means (34', 34'') for detecting a fluorescent image produced by said sample in response to the illunination light. In one embodiment the apparatus further comprises an auto-focus module comprising a laser (38'), a beam splitter cube (86'), a converging lens (90'), and an auto-focus dichroec (94') for maintaining focus of the objective on the sample.
摘要翻译：用于分析单分子存在的装置包括其上具有样品的样品板（30'）。在一个实施例中，该装置包括两个激光器（46'，46“），用于提供适于激发样品中的荧光的两个不同波长的照明光，准直器包括带通滤波器（50'，55”），（74'）引导到样品上的发散透镜（54'，54“），视场光阑（62'）和会聚透镜（66'）， '，34“），用于检测由所述样品响应于所述illunination光而产生的荧光图像。在一个实施例中，该设备还包括自动对焦模块，该自动对焦模块包括用于保持聚焦的激光器（38'），分束器立方体（86'），会聚透镜（90'）和自动对焦二向色镜（94'）样本上的目标。

8. 发明申请

WO2008016906A2 NUCLEOTIDE ANALOGS 审中-公开
标题翻译：核苷酸类似物
公开(公告)号：WO2008016906A2
公开(公告)日：2008-02-07
申请号：PCT/US2007074828
申请日：2007-07-31
申请人： HELICOS BIOSCIENCES CORP , SIDDIQI SUHAIB M , KRZYMANSKA-OLEJNIK EDYTA , ORGUEIRA HERMAN ANTONIO , BAI XIAOPENG
发明人： SIDDIQI SUHAIB M , KRZYMANSKA-OLEJNIK EDYTA , ORGUEIRA HERMAN ANTONIO , BAI XIAOPENG
CPC分类号： C07H19/04 , C07H19/10 , C07H19/20 , C07H19/207
摘要： The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.
摘要翻译：本发明提供了用于测序核酸分子的核苷酸类似物。

9. 发明申请

WO2007019479A3 MULTI-CHANNEL FLOW CELLS 审中-公开
标题翻译：多通道流动细胞
公开(公告)号：WO2007019479A3
公开(公告)日：2007-09-20
申请号：PCT/US2006030824
申请日：2006-08-04
申请人： HELICOS BIOSCIENCES CORP , LAWSON JOHN , WELLMAN PARRIS , KIANI SEPEHR
发明人： LAWSON JOHN , WELLMAN PARRIS , KIANI SEPEHR
IPC分类号： F15C1/06 , C12M1/36 , C12M3/00
CPC分类号： B01L3/502715 , B01J2219/00522 , B01J2219/00605 , B01J2219/00621 , B01L3/5025 , B01L3/502761 , B01L2200/027 , B01L2300/0636 , B01L2300/0816 , B01L2300/0829 , B01L2300/0877 , B01L2300/0887 , B01L2300/16 , B01L2300/163 , B01L2400/0406 , B01L2400/049 , G01N21/05 , G01N35/1095 , G01N2021/0346
摘要： A multi-channel flow cell can allow for reduced cross-contamination in sample loading and the ability to observe activity within the flow cell once the channels are loaded. A multi-channel flow cell includes a plurality of independently-addressable channels sandwiched between a two substrates. Each of the channels can be coated with a layer that facilitates support-binding of an analyte. Each of the channels terminates on one end in an inlet and on the other end in an outlet. A loading block having inlet ports that match the inlets of the channels can be mated to the inlets of the channels, and an outlet block can be mated to the outlets of the channels. Analytes can be introduced into the channels via the inlet ports of the loading block and are pulled through the channels by capillary action or by vacuum. Once analyte has been introduced into each of the channels, the loading and outlet blocks can be removed and the device turned over. Such a flow cell can be used for streamlining the process of reaction and interrogation of biochemical assays at the microfluidic level. Reagents can be introduced into each of the channels of the flow cell for chemical reactions therein, excess reagent being washed out through the channel outlets. Observation of optically-detectable moieties is then conducted. With such a flow cell optical labels associated with incorporation in a sequencing-by-synthesis reaction can be observed.
摘要翻译：多通道流通池可以允许在样品加载中减少交叉污染，并且一旦加载通道，就能够观察流动池内的活性。多通道流动池包括夹在两个基板之间的多个可独立寻址的通道。每个通道可以涂覆有促进分析物的支持结合的层。每个通道的一端在入口处终止，另一端在出口处终止。具有与通道的入口匹配的入口端口的装载块可以配合到通道的入口，并且出口块可以配合到通道的出口。分析物可以通过装载块的入口引入通道，并通过毛细作用或真空被吸引通过通道。一旦分析物被引入到每个通道中，则可以去除装载和出口块并且将装置翻转。这样的流动池可以用于在微流控水平下精简生物化学测定的反应和询问过程。可以将试剂引入流动池的每个通道中用于其中的化学反应，多余的试剂通过通道出口被洗出。然后进行光学可检测部分的观察。通过这样的流动池，可以观察到与逐步合成反应相结合的光学标记。

10. 发明申请

WO2007103465A2 SYSTEMS AND METHODS FOR REDUCING DETECTED INTENSITY NON-UNIFORMITY IN A LASER BEAM 审中-公开
标题翻译：用于减少激光束中检测强度非均匀性的系统和方法
公开(公告)号：WO2007103465A2
公开(公告)日：2007-09-13
申请号：PCT/US2007005876
申请日：2007-03-07
申请人： HELICOS BIOSCIENCES CORP , WEBER AARON , TRACY DAVID
发明人： WEBER AARON , TRACY DAVID
CPC分类号： G01J1/4257 , G01J1/04 , G01J1/0407 , G01J1/0414 , G01J1/0437 , G01J2001/4261
摘要： A method of increasing the spatial uniformity of the detected intensity of a beam of light from a laser in a system including the laser and a light detector. In one embodiment the method includes the steps of generating a beam of light with the laser; and moving the beam of light and the light detector relative to each other, such that the detector averages the spatial intensity of the beam of light over time. In another embodiment the invention relates to a system for increasing the detected spatial uniformity of the intensity of a beam of light. In one embodiment the system comprises a light detector; a laser source for generating the beam of light; and a means for moving the beam of light and the detector relative to one another such that the detector averages the intensity of the light beam over time
摘要翻译：一种增加在包括激光器和光检测器的系统中来自激光器的光束的检测强度的空间均匀性的方法。在一个实施例中，该方法包括以下步骤：用激光产生光束; 并且相对于彼此移动光束和光检测器，使得检测器随时间平均光束的空间强度。在另一个实施例中，本发明涉及一种用于增加检测到的光束的强度的空间均匀性的系统。在一个实施例中，系统包括光检测器; 用于产生光束的激光源; 以及用于相对于彼此移动光束和检测器的装置，使得检测器随着时间平均光束的强度

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