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1. 发明授权

US08563246B2 Combinatorial decoding of random nucleic acid arrays 有权
公开(公告)号：US08563246B2
公开(公告)日：2013-10-22
申请号：US13532606
申请日：2012-06-25
申请人： Mark S. Chee , David R. Walt
发明人： Mark S. Chee , David R. Walt
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , B01J2219/005 , B01J2219/00572 , B01J2219/00585 , B01J2219/00596 , B01J2219/00648 , B01J2219/00659 , B01J2219/00702 , B01J2219/00722 , C07B2200/11 , C07H21/00 , C12Q1/6837 , C40B20/04 , C40B40/06 , C40B70/00 , C12Q2563/161 , C12Q2563/185 , C12Q2525/179 , C12Q2563/155 , C12Q2565/514
摘要： Methods disclosed herein relate to identification of nucleotides in a nucleotide sequence.

2. 发明授权

US08426217B2 Self-encoding sensor with microspheres 有权
公开(公告)号：US08426217B2
公开(公告)日：2013-04-23
申请号：US13215749
申请日：2011-08-23
申请人： David R. Walt , Todd A. Dickinson
发明人： David R. Walt , Todd A. Dickinson
IPC分类号： G01N21/00 , G01N33/543 , G01N21/75
CPC分类号： C12Q1/682 , B01J2219/00317 , B01J2219/0045 , B01J2219/00466 , B01J2219/005 , B01J2219/00524 , B01J2219/00585 , B01J2219/00648 , B01J2219/00659 , C12Q1/6834 , C40B60/14 , G01N21/6428 , G01N21/6452 , G01N21/7703 , G01N33/0031 , G01N33/54313 , G01N2201/0846 , Y10T436/101666 , Y10T436/109163
摘要： Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

3. 发明授权

US07595473B2 Method and system of array imaging 有权
标题翻译：阵列成像的方法和系统
公开(公告)号：US07595473B2
公开(公告)日：2009-09-29
申请号：US11209432
申请日：2005-08-22
申请人： David R. Walt , Sandra Bencic-Nagale
发明人： David R. Walt , Sandra Bencic-Nagale
IPC分类号： G01N21/00
CPC分类号： G01J3/2803 , G01J3/02 , G01J3/0213 , G01J3/0229 , G01J3/10 , G01J3/4406 , G01J2001/0276 , G01N21/6428 , G01N21/6458 , G01N2021/6441 , G01N2021/6484 , G01N2201/08 , G01N2201/088
摘要： The present invention relates to a method and system of array imaging that extends or maximizes the longevity of the sensor array by minimizing the effects of photobleaching. The imaging system has a light source, a variable exposure aperture, and a variable filter system. The system extends the longevity of sensors by (1) using the variable exposure aperture to selectively expose sections of the sensor array containing representative numbers of each type of sensor, and/or (2) using the variable filter system to control the intensity of the excitation light, providing only the intensity required to induce the appropriate excitation and increasing that intensity over time as necessary to counteract the effects of photobleaching.
摘要翻译：本发明涉及阵列成像的方法和系统，该方法和系统通过最小化光漂白的影响来延长或最大化传感器阵列的寿命。成像系统具有光源，可变曝光孔径和可变过滤器系统。该系统通过（1）使用可变曝光孔径来延长传感器的寿命，以选择性地暴露包含每种类型的传感器的代表数的传感器阵列的部分，和/或（2）使用可变过滤器系统来控制传感器的强度激发光，仅提供诱导适当激发所需的强度，并根据需要随时间增加强度以抵消光漂白的影响。

4. 发明申请

US20090201499A1 Spectroscopic Imaging Microscopy 有权
标题翻译：光谱成像显微镜
公开(公告)号：US20090201499A1
公开(公告)日：2009-08-13
申请号：US12239628
申请日：2008-09-26
申请人： David J. Monk , David R. Walt
发明人： David J. Monk , David R. Walt
IPC分类号： G01J3/04
CPC分类号： G01J3/18 , G01J3/02 , G01J3/0208 , G01J3/0229 , G01J3/0237 , G01J3/0264 , G01J3/14 , G01J3/32 , G02B21/06 , G02B21/367
摘要： Disclosed herein are systems that include: (a) an objective lens system configured to collect light from a sample; (b) a first aperture positioned to allow a portion of the collected light received from the objective lens system to pass as input light; (c) a first lens positioned to transmit the input light received from the first aperture; (d) a dispersive element configured to spatially disperse the input light received from the first lens in a first plane; (e) a second lens positioned to transmit the spatially dispersed light; (f) a second aperture positioned to allow a portion of the spatially dispersed light received from the second lens to pass as detection light; and (g) a detector positioned to receive the detection light and configured to form at least one image of the sample.
摘要翻译：这里公开的系统包括：（a）被配置为收集来自样品的光的物镜系统; （b）第一孔，定位成允许从物镜系统接收的一部分收集的光作为输入光通过; （c）第一透镜，定位成透射从第一孔接收的输入光; （d）分散元件，被配置为在第一平面中将从第一透镜接收的输入光空间分散; （e）定位成透射空间分散的光的第二透镜; （f）第二孔，定位成允许从第二透镜接收的部分空间分散的光作为检测光通过; 和（g）定位成接收检测光并被配置成形成样品的至少一个图像的检测器。

5. 发明申请

US20090156425A1 METHODS FOR DETECTING TARGET ANALYTES AND ENZYMATIC REACTIONS 审中-公开
标题翻译：检测目标分析和酶活性的方法
公开(公告)号：US20090156425A1
公开(公告)日：2009-06-18
申请号：US12371449
申请日：2009-02-13
申请人： David R. Walt , Karri Lynn Michael-Ballard
发明人： David R. Walt , Karri Lynn Michael-Ballard
IPC分类号： C40B30/04
CPC分类号： G01N15/1456 , B01J19/0046 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/005 , B01J2219/00524 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00648 , B01J2219/00659 , B01J2219/00677 , B01J2219/00704 , B01J2219/00722 , B01J2219/00725 , B01J2219/0074 , B82Y30/00 , C12Q1/6837 , C40B40/06 , C40B40/10 , G01N21/6428 , G01N21/6452 , G01N21/6456 , G01N21/7703 , G01N21/78 , G01N33/543 , G01N33/54313 , G01N2015/1438 , G01N2021/6441 , G01N2021/6484 , G01N2035/0097 , G01N2201/0826 , Y02A50/55 , Y10S435/808 , Y10S436/805
摘要： A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.
摘要翻译：公开了一种基于微球的分析化学体系及其制备方法，其中携带生物活性剂的微球或颗粒可以随机或以有序的方式组合并分散在基质上以形成阵列，同时保持识别生物活性物质的位置的能力阵列内的代理和粒子，使用光学可询问的光学签名编码方案。可以使用各种各样的改性底物，其提供用于以随机或图案分布容纳微球体的离散或非离散位点。衬底可以由各种材料构成以形成二维或三维构型。在优选的实施方案中，采用改性的光纤束或阵列作为基底以产生高密度阵列。所公开的系统和方法具有检测目标分析物和筛选大型生物活性剂库的效用。

6. 发明申请

US20090149341A1 METHODS FOR DETECTING TARGET ANALYTES AND ENZYMATIC REACTIONS 审中-公开
公开(公告)号：US20090149341A1
公开(公告)日：2009-06-11
申请号：US12265697
申请日：2008-11-05
申请人： David R. Walt , Karri Lynn Michael-Ballard
发明人： David R. Walt , Karri Lynn Michael-Ballard
IPC分类号： C40B30/04 , C40B30/08 , C40B30/10
CPC分类号： G01N15/1456 , B01J19/0046 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/005 , B01J2219/00524 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00648 , B01J2219/00659 , B01J2219/00677 , B01J2219/00704 , B01J2219/00722 , B01J2219/00725 , B01J2219/0074 , B82Y30/00 , C12Q1/6837 , C40B40/06 , C40B40/10 , G01N21/6428 , G01N21/6452 , G01N21/6456 , G01N21/7703 , G01N21/78 , G01N33/543 , G01N33/54313 , G01N2015/1438 , G01N2021/6441 , G01N2021/6484 , G01N2035/0097 , G01N2201/0826 , Y02A50/55 , Y10S435/808 , Y10S436/805
摘要： A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.

7. 发明授权

US07115884B1 Self-encoding fiber optic sensor 失效
标题翻译：自编光纤传感器
公开(公告)号：US07115884B1
公开(公告)日：2006-10-03
申请号：US08944850
申请日：1997-10-06
申请人： David R. Walt , Todd A. Dickinson
发明人： David R. Walt , Todd A. Dickinson
IPC分类号： G01N21/64
CPC分类号： G01N21/6452 , B01J2219/00317 , B01J2219/00524 , B01J2219/00648 , B01J2219/00659 , C40B60/14 , G01N21/6428 , G01N21/7703 , G01N33/0031 , G01N33/54313 , G01N33/54373 , G01N33/54393 , G01N2021/6484 , G01N2021/7786
摘要： Self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme, resulting in a microsphere-based analytic chemistry system. Individual microsphere sensors are disposed in microwells at a distal end of a fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle to form an optical fiber bundle sensor. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and signal-to-noise ratios.
摘要翻译：具有针对特定目标分析物的特征性光学响应特征的自编码微球可以混合在一起，同时保留能力以在传感器阵列中使用光学方法识别大量这种传感器的随机色散中的每个传感器的传感器类型和位置可询问的编码方案，导致基于微球的分析化学系统。单个微球传感器设置在纤维束的远端处的微孔中，并且光学耦合到束内的离散纤维或纤维组，以形成光纤束传感器。阵列中各个传感器的身份通过将阵列暴露于参考分析物而进行自编码，同时用激发光能照射阵列。单个传感器阵列可以携带数千个离散感测元件，其组合信号提供传感器检测限，响应时间和信噪比方面的实质性改进。

8. 发明授权

US06859570B2 Target analyte sensors utilizing microspheres 有权
标题翻译：使用微球的目标分析物传感器
公开(公告)号：US06859570B2
公开(公告)日：2005-02-22
申请号：US09925292
申请日：2001-08-08
申请人： David R. Walt , Karri L. Michael
发明人： David R. Walt , Karri L. Michael
IPC分类号： G01N21/64 , B01J19/00 , C12M1/40 , C12Q1/00 , C12Q1/68 , C40B40/06 , C40B40/10 , C40B60/14 , G01N1/28 , G01N15/14 , G01N21/77 , G01N33/15 , G01N33/50 , G01N33/53 , G01N33/532 , G01N33/543 , G01N33/566 , G01N33/58 , G01N35/00 , G01N37/00 , G02B6/26
CPC分类号： G01N33/54346 , B01J19/0046 , B01J2219/00317 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B60/14 , G01N15/1456 , G01N15/1459 , G01N15/1468 , G01N21/6428 , G01N21/6452 , G01N21/7703 , G01N33/543 , G01N2015/1438 , G01N2015/1465 , G01N2035/0097 , Y10S359/90 , Y10S435/808
摘要： A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.
摘要翻译：公开了一种基于微球的分析化学体系及其制备方法，其中携带生物活性剂的微球或颗粒可以随机或以有序的方式组合并分散在基质上以形成阵列，同时保持识别生物活性物质的位置的能力阵列内的代理和粒子，使用光学可询问的光学签名编码方案。可以使用各种各样的改性底物，其提供用于以随机或图案分布容纳微球体的离散或非离散位点。衬底可以由各种材料构成以形成二维或三维构型。在优选的实施方案中，采用改性的光纤束或阵列作为基底以产生高密度阵列。所公开的系统和方法具有检测目标分析物和筛选大型生物活性剂库的效用。

9. 发明授权

US06620584B1 Combinatorial decoding of random nucleic acid arrays 有权
公开(公告)号：US06620584B1
公开(公告)日：2003-09-16
申请号：US09574117
申请日：2000-05-19
申请人： Mark Chee , David R. Walt
发明人： Mark Chee , David R. Walt
IPC分类号： C12Q168
CPC分类号： C12Q1/6874 , B01J2219/005 , B01J2219/00572 , B01J2219/00585 , B01J2219/00596 , B01J2219/00648 , B01J2219/00659 , B01J2219/00702 , B01J2219/00722 , C07B2200/11 , C07H21/00 , C12Q1/6837 , C40B20/04 , C40B40/06 , C40B70/00 , C12Q2563/161 , C12Q2563/185 , C12Q2525/179 , C12Q2563/155 , C12Q2565/514
摘要： The invention provides methods and compositions for combinatorially decoding arrays.

10. 发明授权

US06482593B2 Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample 有权
标题翻译：用于选择性地检测混合流体样品中的寡核苷酸种类的光纤生物传感器
公开(公告)号：US06482593B2
公开(公告)日：2002-11-19
申请号：US09187289
申请日：1998-11-05
申请人： David R. Walt , Brian G. Healey
发明人： David R. Walt , Brian G. Healey
IPC分类号： C12Q168
CPC分类号： G01N21/7703 , G01N2201/0833 , Y10S977/924
摘要： The present invention provides biosensors, apparatus and methods for selectively detecting at least one complementary oligonucleotide target specie in a fluid sample containing a mixture of different oligonucleotide fragments. One preferred embodiment of the biosensor is as a unitary fiber optic array having species of single stranded nucleic acid disposed as individual deposits in aligned organization upon multiple strand end faces at differing spatial positions on the distal array end surface.
摘要翻译：本发明提供用于选择性检测含有不同寡核苷酸片段的混合物的流体样品中的至少一种互补寡核苷酸靶物种的生物传感器，装置和方法。生物传感器的一个优选实施方案是作为单一的光纤阵列，其具有作为单独沉积物的单链核酸的种类，其排列组织在远端阵列端表面上的不同空间位置处的多股端面上。

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