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1. 发明授权

US07863052B2 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 有权
公开(公告)号：US07863052B2
公开(公告)日：2011-01-04
申请号：US11490556
申请日：2006-07-20
申请人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： G01N33/551
CPC分类号： G01N21/648 , G01N21/552 , G01N21/6428 , G01N21/7743 , Y10S435/808 , Y10S436/805 , Y10T436/143333
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.

2. 发明申请

US20100143959A1 GRATING BASED SENSOR COMBINING LABEL-FREE BINDING DETECTION AND FLUORESNCE AMPLIFICATION AND READOUT SYSTEM FOR SENSOR 审中-公开
标题翻译：基于光栅的传感器组合无线绑定检测和荧光灯放大和读取传感器系统
公开(公告)号：US20100143959A1
公开(公告)日：2010-06-10
申请号：US12451724
申请日：2008-06-03
申请人： Brian T Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath , Brant Binder
发明人： Brian T Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath , Brant Binder
IPC分类号： C12Q1/02 , C12M1/34
CPC分类号： G01N21/6452 , G01N21/648 , G01N21/76 , G01N21/7743 , G01N33/54373 , G01N33/6872 , Y10S436/805
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. Various applications for the biosensors are described, including cell-based assays for assessing the effect of drug compounds, proteins, peptides and other materials on cell function. A biosensor embodiment optimized for a luminescent response at two different wavelengths is also described. Such luminescent response could be produced by fluorescence (either native or from an attached fluorophore), phosphorescence, chemi-luminescence, or other luminescence technology. Two different luminescence technologies could be combined on the same biosensor chip.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。描述了用于生物传感器的各种应用，包括用于评估药物化合物，蛋白质，肽和其他材料对细胞功能的影响的基于细胞的测定。还描述了针对两个不同波长的发光响应进行了优化的生物传感器实施例。这种发光反应可以通过荧光（天然的或来自附着的荧光团），磷光，化学发光或其他发光技术产生。两种不同的发光技术可以组合在相同的生物传感器芯片上。

3. 发明申请

US20080240543A1 Calibration and normalization method for biosensors 审中-公开
标题翻译：生物传感器的校正和归一化方法
公开(公告)号：US20080240543A1
公开(公告)日：2008-10-02
申请号：US12077809
申请日：2008-03-20
申请人： Wolfgang Ernst Gustav Budach , Dieter Neuschafer , Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Wolfgang Ernst Gustav Budach , Dieter Neuschafer , Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： G06K9/00
CPC分类号： G01N33/54373 , B01L3/5085 , G01N21/4788 , G01N21/552 , G01N21/554 , G01N21/6428 , G01N21/645 , G01N21/648 , G01N21/7743
摘要： Calibration and normalization methods for a grating-based sensor design are disclosed. The sensor may be constructed in a manner optimized for both label-free and luminescence, e.g. fluorescence, amplification detection in a single device. Such a sensor, based on grating or another periodical structure with appropriate coating, dramatically increases the diversity of applications and allows realizing novel concepts that provide qualitative and quantitative information/data for each location or capture element in the sensor surface. The invention takes advantage of these different modes to carry out a quality control (QC) step and a calibration of each individual location of the sensor. Thus, the assay data can be flagged according to their quality and local density variations, batch variations and variations in the printed deposition of probes or the materials to the surface can be compensated.
摘要翻译：公开了基于光栅的传感器设计的校准和归一化方法。传感器可以以针对无标记和发光两者而优化的方式来构造。荧光，放大检测在单个器件中。这种基于光栅或具有适当涂层的周期性结构的传感器显着地增加了应用的多样性，并且实现了为传感器表面中的每个位置或捕获元件提供定性和定量的信息/数据的新概念。本发明利用这些不同的模式来执行传感器的每个单独位置的质量控制（QC）步骤和校准。因此，可以根据其质量和局部密度变化标记测定数据，可以补偿探针的印刷沉积或表面的材料的批量变化和变化。

4. 发明申请

US20100227769A1 GRATING-BASED SENSOR COMBINING LABEL-FREE BINDING DETECTION AND FLUORESCENCE AMPLIFICATION AND READOUT SYSTEM FOR SENSOR 有权
标题翻译：基于GRATING的传感器组合无标签绑定检测和荧光放大和读取传感器系统
公开(公告)号：US20100227769A1
公开(公告)日：2010-09-09
申请号：US11490556
申请日：2006-07-20
申请人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： C40B30/04 , G01N30/00 , C12M1/34 , C40B60/12 , G01N21/00 , G01N33/00 , C12Q1/70 , G01N33/48 , G01N33/543 , C12Q1/02 , G01N33/567 , G01N33/554 , G01N21/55 , G01J3/28
CPC分类号： G01N21/648 , G01N21/552 , G01N21/6428 , G01N21/7743 , Y10S435/808 , Y10S436/805 , Y10T436/143333
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。公开了一些实施例，其被优化用于空气模式中的ER检测，其中样品是干的。其他实施方案针对液体模式中的ER检测进行了优化，其中将样品悬浮在诸如水的液体介质中。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。一个实施例包括优化用于收集无标记检测数据的第一光源，为采集ER荧光放大数据而优化的第二光源和至少一个检测器。在一个实施例中，检测器是成像系统，并且包括用于收集ER和无标签数据的CCD照相机。在其他实施例中，至少一个检测器采用用于收集无标签数据的光谱仪的形式和用于收集ER数据的光电倍增管。在其他实施例中，使用诸如可调激光器或宽带光源的单个光源。

5. 发明申请

US20100003743A1 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 有权
标题翻译：光栅传感器结合无标签结合检测和荧光放大和传感器读出系统
公开(公告)号：US20100003743A1
公开(公告)日：2010-01-07
申请号：US12387391
申请日：2009-04-30
申请人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： C12M1/34
CPC分类号： G01N21/648 , G01N21/552 , G01N21/6428 , G01N21/7743 , Y10S435/808 , Y10S436/805 , Y10T436/143333
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。公开了一些实施例，其被优化用于空气模式中的ER检测，其中样品是干的。其他实施方案针对液体模式中的ER检测进行了优化，其中将样品悬浮在诸如水的液体介质中。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。一个实施例包括优化用于收集无标记检测数据的第一光源，为采集ER荧光放大数据而优化的第二光源和至少一个检测器。在一个实施例中，检测器是成像系统，并且包括用于收集ER和无标签数据的CCD照相机。在其他实施例中，至少一个检测器采用用于收集无标签数据的光谱仪的形式和用于收集ER数据的光电倍增管。在其他实施例中，使用诸如可调激光器或宽带光源的单个光源。

6. 发明授权

US07960170B2 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 有权
标题翻译：光栅传感器结合无标签结合检测和荧光放大和传感器读出系统
公开(公告)号：US07960170B2
公开(公告)日：2011-06-14
申请号：US12387391
申请日：2009-04-30
申请人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： C12M1/34
CPC分类号： G01N21/648 , G01N21/552 , G01N21/6428 , G01N21/7743 , Y10S435/808 , Y10S436/805 , Y10T436/143333
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。公开了一些实施例，其被优化用于空气模式中的ER检测，其中样品是干的。其他实施方案针对液体模式中的ER检测进行了优化，其中将样品悬浮在诸如水的液体介质中。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。一个实施例包括优化用于收集无标记检测数据的第一光源，为采集ER荧光放大数据而优化的第二光源和至少一个检测器。在一个实施例中，检测器是成像系统，并且包括用于收集ER和无标签数据的CCD照相机。在其他实施例中，至少一个检测器采用用于收集无标记数据的光谱仪的形式和用于收集ER数据的光电倍增管。在其他实施例中，使用诸如可调激光器或宽带光源的单个光源。

7. 发明申请

US20100329933A1 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 审中-公开
标题翻译：光栅传感器结合无标签结合检测和荧光放大和传感器读出系统
公开(公告)号：US20100329933A1
公开(公告)日：2010-12-30
申请号：US12804525
申请日：2010-07-22
申请人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
发明人： Stephen C. Schulz , Brian T. Cunningham , Lance G. Laing , Peter Y. Li , Brant Binder , Gangadhar Jogikalmath , Alex Borsody
IPC分类号： G01N21/00
CPC分类号： G01N21/648 , G01N21/552 , G01N21/6428 , G01N21/7743 , Y10S435/808 , Y10S436/805 , Y10T436/143333
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is in the form of an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。公开了一些实施例，其被优化用于空气模式中的ER检测，其中样品是干的。其他实施方案针对液体模式中的ER检测进行了优化，其中将样品悬浮在诸如水的液体介质中。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。一个实施例包括优化用于收集无标记检测数据的第一光源，为采集ER荧光放大数据而优化的第二光源和至少一个检测器。在一个实施例中，检测器是成像系统的形式，并且包括用于收集ER和无标签数据的CCD照相机。在其他实施例中，至少一个检测器采用用于收集无标签数据的光谱仪的形式和用于收集ER数据的光电倍增管。在其他实施例中，使用诸如可调激光器或宽带光源的单个光源。

8. 发明申请

US20090226950A1 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 失效
标题翻译：光栅传感器结合无标签结合检测和荧光放大和传感器读出系统
公开(公告)号：US20090226950A1
公开(公告)日：2009-09-10
申请号：US11818742
申请日：2007-06-15
申请人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
发明人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
IPC分类号： C12Q1/02 , C12M1/34
CPC分类号： G01N21/6452 , G01N21/648 , G01N21/76 , G01N21/7743 , G01N33/54373 , G01N33/6872 , Y10S436/805
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. Various applications for the biosensors are described, including cell-based assays for assessing the effect of drug compounds on cell function. A biosensor embodiment optimized for a luminescent response at two different wavelengths is also described. Such luminescent response could be produced by fluorescence (either native or from an attached fluorophore), phosphorescence, chemi-luminescence, or other luminescence technology. Two different luminescence technologies could be combined on the same biosensor chip.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。描述了用于生物传感器的各种应用，包括用于评估药物化合物对细胞功能的影响的基于细胞的测定。还描述了针对两个不同波长的发光响应进行了优化的生物传感器实施例。这种发光反应可以通过荧光（天然的或来自附着的荧光团），磷光，化学发光或其他发光技术产生。两种不同的发光技术可以组合在相同的生物传感器芯片上。

9. 发明授权

US07790406B2 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 失效
标题翻译：光栅传感器结合无标签结合检测和荧光放大和传感器读出系统
公开(公告)号：US07790406B2
公开(公告)日：2010-09-07
申请号：US11818742
申请日：2007-06-15
申请人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
发明人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
IPC分类号： G01N33/551
CPC分类号： G01N21/6452 , G01N21/648 , G01N21/76 , G01N21/7743 , G01N33/54373 , G01N33/6872 , Y10S436/805
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. Various applications for the biosensors are described, including cell-based assays for assessing the effect of drug compounds on cell function. A biosensor embodiment optimized for a luminescent response at two different wavelengths is also described. Such luminescent response could be produced by fluorescence (either native or from an attached fluorophore), phosphorescence, chemi-luminescence, or other luminescence technology. Two different luminescence technologies could be combined on the same biosensor chip.
摘要翻译：公开了一种光栅传感器，其具有构造和设计用于ev逝共振（ER）荧光检测和无标签检测应用的光栅结构。还公开了一维和二维光栅，包括以具有中心柱，中心孔和两层二维光栅的单元电池为特征的光栅。还公开了一种用于这种传感器的读出系统。描述了用于生物传感器的各种应用，包括用于评估药物化合物对细胞功能的影响的基于细胞的测定。还描述了针对两个不同波长的发光响应进行了优化的生物传感器实施例。这种发光反应可以通过荧光（天然的或来自附着的荧光团），磷光，化学发光或其他发光技术产生。两种不同的发光技术可以组合在相同的生物传感器芯片上。

10. 发明申请

US20100202923A1 Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor 审中-公开
公开(公告)号：US20100202923A1
公开(公告)日：2010-08-12
申请号：US12799289
申请日：2010-04-20
申请人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
发明人： Brian T. Cunningham , Peter Y. Li , Lance G. Laing , Gangadhar Jogikalmath
IPC分类号： G01N21/76 , G01N21/64 , G01N21/66
CPC分类号： G01N21/6452 , G01N21/648 , G01N21/76 , G01N21/7743 , G01N33/54373 , G01N33/6872 , Y10S436/805
摘要： A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. Various applications for the biosensors are described, including cell-based assays for assessing the effect of drug compounds on cell function. A biosensor embodiment optimized for a luminescent response at two different wavelengths is also described. Such luminescent response could be produced by fluorescence (either native or from an attached fluorophore), phosphorescence, chemi-luminescence, or other luminescence technology. Two different luminescence technologies could be combined on the same biosensor chip.

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