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11. 发明申请

US20080058512A1 APPARATUSES AND METHODS FOR OLIGONUCLEOTIDE PREPARATION 有权
标题翻译：用于寡核苷酸制备的装置和方法
公开(公告)号：US20080058512A1
公开(公告)日：2008-03-06
申请号：US11469405
申请日：2006-08-31
申请人： Eric M. Leproust
发明人： Eric M. Leproust
IPC分类号： C07H21/00 , C12M1/34
CPC分类号： C07H21/00
摘要： Provided are improved processes and apparatuses for solid phase oligonucleotide synthesis, the improvements comprising carrying out detritylation of the nascent oligonucleotide using a composition of an organic solvent, a protic solvent and a selected concentration, or selected concentration range, of water. In some embodiments, an oligonucleotide synthesis apparatus includes means for adding water to a detritylation reagent. In some embodiments, an apparatus can include a water detector for analyzing the water concentration of a detritylation reagent to be reacted with a nascent oligonucleotide. An apparatus can comprise a feedback loop to control the concentration of water at the point of the detritylation reaction and/or to control the detritylation reaction time. The apparatuses and methods reduce batch-to-batch variations in the manufacture of oligonucleotides immobilized on the surface of various substrates
摘要翻译：提供了用于固相寡核苷酸合成的改进的方法和装置，其改进包括使用有机溶剂，质子溶剂和所选浓度或选定浓度范围的水进行新生寡核苷酸的去结合。在一些实施方案中，寡核苷酸合成装置包括向去离子化试剂中加入水的装置。在一些实施例中，装置可以包括用于分析与新生寡核苷酸反应的去离子试剂的水浓度的水检测器。装置可以包括反馈回路以控制在去离子化反应的点处的水的浓度和/或控制不稳定反应时间。这些装置和方法减少了固定在各种底物表面上的寡核苷酸制造中的批次间变化

12. 发明申请

US20080241829A1 Methods And Kits For Producing Labeled Target Nucleic Acid For Use In Array Based Hybridization Applications 审中-公开
标题翻译：用于生产标记靶核酸的方法和试剂盒用于基于阵列的杂交应用
公开(公告)号：US20080241829A1
公开(公告)日：2008-10-02
申请号：US11695201
申请日：2007-04-02
申请人： Stephen B. Milligan , Eric M. Leproust
发明人： Stephen B. Milligan , Eric M. Leproust
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q2533/101 , C12Q2525/149 , C12Q2565/501
摘要： Methods for producing labeled probe nucleic acids from genomic nucleic acid template are provided. In some embodiments of the subject methods, a plurality of sequence-specific primers are employed to enzymatically generate a set of labeled target nucleic acids corresponding to coding regions of genes from a genomic template via a primer extension protocol. The subject methods find use in a variety of different applications, and can be used, for example, in the preparation of labeled probe nucleic acids for use in array based comparative genomic hybridization applications. Also provided are kits for use in practicing the subject methods.
摘要翻译：提供了从基因组核酸模板生产标记探针核酸的方法。在本发明方法的一些实施方案中，使用多个序列特异性引物来通过引物延伸方案酶解产生对应于来自基因组模板的基因的编码区的一组标记的靶核酸。本发明方法可用于各种不同的应用，并且可以用于例如用于基于阵列的比较基因组杂交应用中的标记探针核酸的制备。还提供了用于实践主题方法的套件。

13. 发明授权

US07252938B2 Methods and devices for producing a polymer at a location of a substrate 失效
标题翻译：在基材的位置处制备聚合物的方法和装置
公开(公告)号：US07252938B2
公开(公告)日：2007-08-07
申请号：US10374857
申请日：2003-02-25
申请人： Eric M. Leproust , Douglas A. Amorese
发明人： Eric M. Leproust , Douglas A. Amorese
IPC分类号： C12Q1/00 , C12Q1/68 , C12M1/36 , C12M3/00 , G01N33/53 , G01N33/566 , G01N33/543 , G01N33/551 , G01N33/544 , G01N21/00 , G01N21/75 , G01N21/76
CPC分类号： B01J19/0046 , B01J2219/00378 , B01J2219/00576 , B01J2219/00691 , B01J2219/00693 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B60/14 , Y10S436/807 , Y10S436/809
摘要： Methods and devices for producing a polymer at a location of a substrate are provided. In the subject methods, a fluid droplet containing a first monomer labeled with a first detectable label is deposited from a fluid deposition device onto a location of a substrate surface having a second monomer labeled with a second detectable label. The first and second detectable labels are then detected to determine any misalignment between the fluid deposition device and the location of the substrate surface during deposition. Also provided are algorithms that perform the subject methods, as well as fluid deposition devices that include the subject algorithms. The subject invention also includes arrays produced according to the subject methods and kits that include the subject arrays.
摘要翻译：提供了在基板的位置处制造聚合物的方法和装置。在本发明方法中，将含有用第一可检测标记物标记的第一单体的流体液滴从流体沉积装置沉积到具有用第二可检测标记物标记的第二单体的基底表面的位置。然后检测第一和第二可检测标记以确定在沉积期间流体沉积装置与基底表面的位置之间的任何未对准。还提供了执行主题方法的算法，以及包括主题算法的流体沉积设备。本发明还包括根据主题方法和包括主题阵列的试剂盒制备的阵列。

14. 发明授权

US07094537B2 Micro arrays with structured and unstructured probes 失效
公开(公告)号：US07094537B2
公开(公告)日：2006-08-22
申请号：US10136773
申请日：2002-04-30
申请人： Eric M. Leproust , David L. Hirschberg , Glenda C. Delenstarr
发明人： Eric M. Leproust , David L. Hirschberg , Glenda C. Delenstarr
IPC分类号： C12Q1/68 , C12M1/36 , C07H21/04
CPC分类号： C40B30/04 , B01J19/0046 , B01J2219/00274 , B01J2219/00378 , B01J2219/00387 , B01J2219/00549 , B01J2219/00576 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00662 , B01J2219/00675 , B01J2219/00677 , B01J2219/00707 , B01J2219/00722 , B01J2219/00725 , B01J2219/00731 , B82Y30/00 , C40B40/06 , C40B40/10 , C40B40/12 , C40B50/14 , C40B60/14
摘要： The invention provides an apparatus and method for determining a signal produced by a micro array device. The apparatus provides an unstructured probe and structured probe. The unstructured probe binds to a target and provides a first signal that can be compared to a second signal produced by a structured probe. A more accurate level of intensity of the first signal can be determined by comparing to the second signal produced by the structured probe. A method for determining a more accurate level of signal intensity produced from the unstructured probes bound to the target is also disclosed.

15. 发明授权

US07070932B2 Methods and devices for detecting printhead misalignment of an in situ polymeric array synthesis device 失效
标题翻译：用于检测原位聚合物阵列合成装置的打印头未对准的方法和装置
公开(公告)号：US07070932B2
公开(公告)日：2006-07-04
申请号：US10374307
申请日：2003-02-25
申请人： Eric M. Leproust , Douglas A. Amorese , Mel N. Kronick
发明人： Eric M. Leproust , Douglas A. Amorese , Mel N. Kronick
IPC分类号： C07H21/04 , C12Q1/68
CPC分类号： C12Q1/6837 , C12Q2525/173
摘要： Methods and devices for detecting deposition unit misalignment, e.g., printhead misalignment, of an in situ polymeric, e.g., a nucleic acid, array synthesis device are provided. In accordance with the subject methods, at least one test probe feature is synthesized on a substrate using an in situ polymeric array, e.g., nucleic acid array or protein array, synthesis device. The at least one test probe feature is then contacted with at least two different distinguishably labeled targets, e.g., target nucleic acids. The binding of the targets to the at least one test probe feature is then evaluated to detect any misalignment, e.g., deposition unit or pulse jet misalignments, of the synthesis device. Also provided are substrates having at least one test probe feature and at least one polymeric array, as well as methods of using the substrates in array assays. Also included are kits for use in practicing the subject methods.
摘要翻译：提供了用于检测原位聚合物例如核酸阵列合成装置的沉积单元未对准（例如，打印头未对准）的方法和装置。根据本发明的方法，使用原位聚合物阵列，例如核酸阵列或蛋白质阵列，合成装置，在底物上合成至少一种测试探针特征。然后将至少一个测试探针特征与至少两个不同的可区分标记的靶，例如靶核酸接触。然后评估目标与至少一个测试探针特征的结合以检测合成装置的任何未对准，例如沉积单元或脉冲射流未对准。还提供了具有至少一个测试探针特征和至少一个聚合物阵列的基底，以及在阵列测定中使用底物的方法。还包括用于实践主题方法的工具包。

16. 发明授权

US06939673B2 Manufacture of arrays with reduced error impact 失效
标题翻译：减少误差影响的阵列的制造
公开(公告)号：US06939673B2
公开(公告)日：2005-09-06
申请号：US10172468
申请日：2002-06-14
申请人： Jay K. Bass , Maryam Mobed-Miremadi , Eric M. Leproust
发明人： Jay K. Bass , Maryam Mobed-Miremadi , Eric M. Leproust
IPC分类号： B01J19/00 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14 , G01N35/10 , C07H21/04 , C12Q1/68
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/0036 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00637 , B01J2219/00675 , B01J2219/00691 , B01J2219/00693 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B50/14 , C40B60/14 , G01N35/1011 , G01N35/1016 , G01N35/1074 , G01N2035/1034
摘要： Methods and apparatus are disclosed for synthesizing a purality of compounds such as biopolymers on the surface of supports. The synthesis comprises a plurality of steps in which reagents for conducting the synthesis are deposited o the surface of the support to form precursors of the chemical compounds and, ultimately, the chemical compounds themselves. An error in the deposition may occur in one or more of the plurality of steps. A reagent for forming the chemical compounds is deposited on the surface of the support. A determination is made as to whether an error occurred in the depositing of the reagent. If an error is detected, the support is treated to re-deposit at least some of those reagents that were not correctly deposited. In one approach the support is treated to stabilize precursors of the chemical compounds, the source of the error is corrected, and the reagent applied above is re-deposited on the surface.
摘要翻译：公开了用于在载体表面上合成多种化合物如生物聚合物的方法和装置。该合成包括多个步骤，其中用于进行合成的试剂沉积在载体的表面上以形成化合物的前体，最终化学化合物本身。沉积中的错误可能发生在多个步骤中的一个或多个步骤中。用于形成化合物的试剂沉积在载体的表面上。确定在试剂的沉积中是否发生错误。如果检测到错误，则处理支持物以重新沉积至少一些未正确沉积的试剂。在一种方法中，处理支持物以稳定化学化合物的前体，校正错误的来源，并且将上面施加的试剂重新沉积在表面上。

17. 发明授权

US10017879B2 Chemical arrays and methods of using the same 有权
公开(公告)号：US10017879B2
公开(公告)日：2018-07-10
申请号：US13116998
申请日：2011-05-26
申请人： Mel N. Kronick , Eric M. Leproust
发明人： Mel N. Kronick , Eric M. Leproust
IPC分类号： C40B50/18 , C40B30/04 , G01N33/543
CPC分类号： C40B30/04 , G01N33/54366
摘要： Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.

18. 发明授权

US07977119B2 Chemical arrays and methods of using the same 有权
标题翻译：化学数组及其使用方法
公开(公告)号：US07977119B2
公开(公告)日：2011-07-12
申请号：US11008384
申请日：2004-12-08
申请人： Mel N. Kronick , Eric M. Leproust
发明人： Mel N. Kronick , Eric M. Leproust
IPC分类号： G01N33/53 , G01N33/532 , G01N33/543 , G01N33/566 , C07K5/00 , C07K14/00 , C07K17/00
CPC分类号： C40B30/04 , G01N33/54366
摘要： Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.
摘要翻译：提供了从初始化学阵列产生产物分子的混合物的方法和组合物。在本发明方法中，表面固定的第一部分的化学阵列经受切割条件，使得产生溶液相第一部分的组合物。然后将所得到的溶液相第一部分的组合物与一种或多种反应物接触以产生不同于第一部分的产物分子的混合物。还提供了用于实践本发明方法的主题方法和试剂盒中使用的阵列。

19. 发明授权

US07588889B2 Chemical arrays and methods of using the same 失效
标题翻译：化学数组及其使用方法
公开(公告)号：US07588889B2
公开(公告)日：2009-09-15
申请号：US11008603
申请日：2004-12-08
申请人： Paul K. Wolber , Robert H. Kincaid , Douglas Amorese , Diane Ilsley-Tyree , Andrew S. Atwell , Mel N. Kronick , Eric M. Leproust
发明人： Paul K. Wolber , Robert H. Kincaid , Douglas Amorese , Diane Ilsley-Tyree , Andrew S. Atwell , Mel N. Kronick , Eric M. Leproust
IPC分类号： C12Q1/68 , C12M1/00 , C07H21/04
CPC分类号： C12Q1/6883 , B01J2219/00497 , B01J2219/00572 , B01J2219/00574 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/00617 , B01J2219/00626 , B01J2219/00659 , B01J2219/00675 , B01J2219/00722 , B82Y30/00 , C12Q1/6806 , C12Q1/6837 , C12Q1/6876 , C12Q2600/158 , C40B40/06 , C40B50/14 , C40B70/00 , C12Q2565/537 , C12Q2525/161 , C12Q2565/525 , C12Q2525/131 , C12Q2521/301
摘要： Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.
摘要翻译：提供了从初始化学阵列产生产物分子的混合物的方法和组合物。在本发明方法中，表面固定的第一部分的化学阵列经受切割条件，使得产生溶液相第一部分的组合物。然后将所得到的溶液相第一部分的组合物与一种或多种反应物接触以产生不同于第一部分的产物分子的混合物。还提供了用于实践本发明方法的主题方法和试剂盒中使用的阵列。

20. 发明授权

US07504213B2 Methods and apparatus for preparing arrays comprising features having degenerate biopolymers 失效
标题翻译：用于制备包括具有简并生物聚合物的特征的阵列的方法和装置
公开(公告)号：US07504213B2
公开(公告)日：2009-03-17
申请号：US10722155
申请日：2003-11-25
申请人： Theodore R. Sana , Eric M. Leproust , Paul K. Wolber
发明人： Theodore R. Sana , Eric M. Leproust , Paul K. Wolber
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02
CPC分类号： C12Q1/6813
摘要： Methods and apparatus are disclosed for synthesizing a plurality of biopolymers at predetermined feature locations on a surface of a substrate. One or more of the feature locations comprises degenerate biopolymers. One or more biopolymer subunit precursors are added, in multiple rounds of subunit additions, at each of multiple feature locations on the surface to form the plurality of biopolymers on the surface. For each feature location comprising degenerate biopolymers, the biopolymer subunit precursors comprise a mixture of biopolymer subunit precursors for forming the degenerate biopolymers at the feature location.
摘要翻译：公开了用于在基材表面上的预定特征位置合成多种生物聚合物的方法和装置。一个或多个特征位置包括简并生物聚合物。在表面上的多个特征位置的每一个处，在多轮亚基添加物中加入一种或多种生物聚合物亚基前体，以在表面上形成多种生物聚合物。对于包含简并生物聚合物的每个特征位置，生物聚合物亚基前体包含用于在特征位置形成简并生物聚合物的生物聚合物亚基前体的混合物。

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