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1. 发明授权

US07608840B2 System and method employing photokinetic techniques in cell biology imaging applications 失效
标题翻译：在细胞生物学成像应用中使用光动力学技术的系统和方法
公开(公告)号：US07608840B2
公开(公告)日：2009-10-27
申请号：US12185775
申请日：2008-08-04
申请人： Paul C. Goodwin , Carl S. Brown , Steven A. Reese
发明人： Paul C. Goodwin , Carl S. Brown , Steven A. Reese
IPC分类号： G01N21/64
CPC分类号： G01N33/582 , G01N15/1475 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G01N33/5005 , G06T5/003 , G06T2207/10064 , G06T2207/30024
摘要： A system and method employing photokinetic techniques in cell biology imaging applications are disclosed. Systems and methods of acquiring image data of an object may comprise: selectively inducing photoactivation of material at a site on the object; performing an optical axis integration scan; simultaneously executing a time delay integration scan sequence; and processing acquired image data in accordance with one or more desired analyses. Various methodologies and applications may include, inter alia, selective photobleaching of a site on the object, diffusion rate, velocity, and wave-front propagation analyses, multi-dimensional analyses of dispersion characteristics, biomolecular binding in cellular organelles, and photoactivation assisted systematic image segmentation for the study of cellular components.
摘要翻译：公开了在细胞生物学成像应用中使用光动力学技术的系统和方法。获取物体的图像数据的系统和方法可以包括：选择性地诱导物体上的物体的材料的光活化; 执行光轴积分扫描; 同时执行时间延迟积分扫描序列; 以及根据一个或多个期望的分析处理获取的图像数据。各种方法和应用可以包括对物体上的位点的选择性漂白，扩散速率，速度和波前传播分析，分散特征的多维分析，细胞器中的生物分子结合和光活化辅助系统图像细胞分析研究的细分。

2. 发明授权

US09720222B2 Calibration targets for microscope imaging 有权
公开(公告)号：US09720222B2
公开(公告)日：2017-08-01
申请号：US13876515
申请日：2011-09-29
申请人： Paul C. Goodwin
发明人： Paul C. Goodwin
IPC分类号： G02B21/34 , G02B23/00 , G02B21/36 , G02B21/02
CPC分类号： G02B21/367 , G02B21/34 , G02B21/365
摘要： This disclosure is directed to optical microscope calibration devices that can be used with optical microscopes to adjust the microscope imaging parameters so that images of samples can be obtained below the diffraction limit. The microscope calibration devices include at least one calibration target. Each calibration target includes a number of features with dimensions below the diffraction limit of a microscope objective. Separate color component diffraction limited images of one of the calibration targets are obtained for a particular magnification. The color component images can be combined and image processed to obtain a focused and non-distorted image of the calibration target. The parameters used to obtain the focused and non-distorted image of the calibration target can be used to obtain focused and non-distorted images of a sample for the same magnification by using the same parameters.

3. 发明授权

US08830314B2 System and method for dense-stochastic-sampling imaging 有权
标题翻译：密集随机抽样成像的系统和方法
公开(公告)号：US08830314B2
公开(公告)日：2014-09-09
申请号：US13535468
申请日：2012-06-28
申请人： Gaudenz Danuser , Paul C. Goodwin
发明人： Gaudenz Danuser , Paul C. Goodwin
IPC分类号： H04N7/18 , G02B21/36 , G01N21/64
CPC分类号： G01N21/6428 , G01N21/636 , G01N21/6458 , G01N2021/6415 , G01N2021/6419 , G01N2201/126 , G02B21/365 , G02B21/367 , G06T3/4053
摘要： Embodiments of the present invention are directed to imaging technologies, and, in particular, to an imaging system that detects relatively weak signals, over time, and that uses the detected signals to determine the positions of signal emitters. Particular embodiments of the present invention are directed to methods and systems for imaging fluorophore-labeled samples in order to produce images of the sample at resolutions significantly greater than the diffraction-limited resolution associated with optical microscopy. Embodiments of the present invention employ overlapping-emitter-image disambiguation to allow data to be collected from densely arranged emitters, which significantly decreases the data-collection time for producing intermediate images as well as the number of intermediate images needed to computationally construct high-resolution final images. Additional embodiments of the present invention employ hierarchical image-processing techniques to further resolve and interpret disambiguated images.
摘要翻译：本发明的实施例涉及成像技术，特别涉及一种随时间检测相对较弱信号的成像系统，并且使用所检测的信号来确定信号发射器的位置。本发明的具体实施方案涉及用于成像荧光团标记的样品的方法和系统，以便以明显大于与光学显微镜相关联的衍射限制分辨率的分辨率产生样品的图像。本发明的实施例采用重叠 - 发射 - 图像消歧以允许从密集布置的发射器收集数据，这显着减少用于产生中间图像的数据收集时间以及计算构建高分辨率所需的中间图像的数量最终图像。本发明的另外的实施例采用分层图像处理技术来进一步解析和解释消歧图像。

4. 发明申请

US20130188035A1 CALIBRATION TARGETS FOR MICROSCOPE IMAGING 有权
标题翻译：用于显微镜成像的校准目标
公开(公告)号：US20130188035A1
公开(公告)日：2013-07-25
申请号：US13876515
申请日：2011-09-29
申请人： Paul C. Goodwin
发明人： Paul C. Goodwin
IPC分类号： G02B21/36 , G02B21/34
CPC分类号： G02B21/367 , G02B21/34 , G02B21/365
摘要： This disclosure is directed to optical microscope calibration devices that can be used with optical microscopes to adjust the microscope imaging parameters so that images of samples can be obtained below the diffraction limit. The microscope calibration devices include at least one calibration target. Each calibration target includes a number of features with dimensions below the diffraction limit of a microscope objective. Separate color component diffraction limited images of one of the calibration targets are obtained for a particular magnification. The color component images can be combined and image processed to obtain a focused and non-distorted image of the calibration target. The parameters used to obtain the focused and non-distorted image of the calibration target can be used to obtain focused and non-distorted images of a sample for the same magnification by using the same parameters.
摘要翻译：本公开涉及可用于光学显微镜以调整显微镜成像参数的光学显微镜校准装置，使得可以在衍射极限以下获得样品的图像。显微镜校准装置包括至少一个校准目标。每个校准目标包括尺寸低于显微镜物镜的衍射极限的许多特征。对于特定的放大倍率，可获得校准目标之一的独立颜色分量衍射限制图像。可以组合颜色分量图像并进行图像处理，以获得校准目标的聚焦和非失真图像。用于获得校准目标的聚焦和非失真图像的参数可以用于通过使用相同的参数来获得相同放大倍率的样本的聚焦和非失真图像。

5. 发明申请

US20110149097A1 SYSTEM AND METHOD FOR DENSE-STOCHASTIC-SAMPLING IMAGING 有权
标题翻译：用于渗透 - 采样成像的系统和方法
公开(公告)号：US20110149097A1
公开(公告)日：2011-06-23
申请号：US12751816
申请日：2010-03-31
申请人： Gaudenz Danuser , Paul C. Goodwin
发明人： Gaudenz Danuser , Paul C. Goodwin
IPC分类号： H04N5/228 , G01J1/58
CPC分类号： G01N21/6428 , G01N21/636 , G01N21/6458 , G01N2021/6415 , G01N2021/6419 , G01N2201/126 , G02B21/365 , G02B21/367 , G06T3/4053
摘要： Embodiments of the present invention are directed to imaging technologies, and, in particular, to an imaging system that detects relatively weak signals, over time, and that uses the detected signals to determine the positions of signal emitters. Particular embodiments of the present invention are directed to methods and systems for imaging fluorophore-labeled samples in order to produce images of the sample at resolutions significantly greater than the diffraction-limited resolution associated with optical microscopy. Embodiments of the present invention employ overlapping-emitter-image disambiguation to allow data to be collected from densely arranged emitters, which significantly decreases the data-collection time for producing intermediate images as well as the number of intermediate images needed to computationally construct high-resolution final images. Additional embodiments of the present invention employ hierarchical image-processing techniques to further resolve and interpret disambiguated images.
摘要翻译：本发明的实施例涉及成像技术，特别涉及一种随时间检测相对较弱信号的成像系统，并且使用所检测的信号来确定信号发射器的位置。本发明的具体实施方案涉及用于成像荧光团标记的样品的方法和系统，以便以明显大于与光学显微镜相关联的衍射限制分辨率的分辨率产生样品的图像。本发明的实施例采用重叠 - 发射 - 图像消歧以允许从密集布置的发射器收集数据，这显着减少用于产生中间图像的数据收集时间以及计算构建高分辨率所需的中间图像的数量最终图像。本发明的另外的实施例采用分层图像处理技术来进一步解析和解释消歧图像。

6. 发明申请

US20090109416A1 DISPERSING IMMERSION LIQUID FOR HIGH RESOLUTION IMAGING AND LITHOGRAPHY 审中-公开
标题翻译：分散液体用于高分辨率成像和平版印刷
公开(公告)号：US20090109416A1
公开(公告)日：2009-04-30
申请号：US12208660
申请日：2008-09-11
申请人： WILLIAM M. DOUGHERTY , Paul C. Goodwin , Steven A. Reese , David A. Stewart
发明人： WILLIAM M. DOUGHERTY , Paul C. Goodwin , Steven A. Reese , David A. Stewart
IPC分类号： G03B27/54 , G02B3/12
CPC分类号： G02B21/33 , G02B21/002 , G02B21/02 , G03F7/70341
摘要： Methods and apparatus are described for delivering index-matching immersion liquid in high numerical-aperture optical microscopy and lithography. An array of immersion liquid droplets is delivered to a specimen substrate or specimen substrate cover by an immersion liquid printing apparatus. An immersion liquid reservoir provides immersion liquid to the printer by a precision pump. The printer delivers immersion liquid to the substrate or substrate cover in arrays of immersion liquid droplets of defined volumes and array patterns. The volumes and patterns of array droplets delivered to the substrate or substrate cover are optimized to maintain adequate immersion liquid between the substrate or substrate cover and an immersion objective while avoiding the formation of air bubbles in the immersion liquid and the accumulation of excess volumes of immersion liquid.
摘要翻译：描述了用于在高数值孔径光学显微镜和光刻中输送折射率匹配浸液的方法和装置。浸没液体液滴的阵列通过浸没液体印刷装置输送到样品基片或样品基片盖。浸没液体储存器通过精密泵向打印机提供浸液。打印机将浸没液体以定义的体积和阵列图案的浸没液滴的阵列传送到基底或基底盖。优化输送到衬底或衬底盖的阵列液滴的体积和图案，以在衬底或衬底盖和浸没物体之间保持足够的浸没液体，同时避免在浸液中形成气泡和积累过量的浸液液体。

7. 发明授权

US07283253B2 Multi-axis integration system and method 有权
标题翻译：多轴整合系统及方法
公开(公告)号：US07283253B2
公开(公告)日：2007-10-16
申请号：US10389269
申请日：2003-03-13
申请人： Steven A. Reese , Carl S. Brown , Paul C. Goodwin
发明人： Steven A. Reese , Carl S. Brown , Paul C. Goodwin
IPC分类号： G01B11/24
CPC分类号： G02B21/367 , G06T1/0007 , H04N5/349 , H04N5/37206 , H04N5/3743
摘要： An image acquisition system and method employing multi-axis integration (MAI) may incorporate both optical axis integration (OAI) and time-delay integration (TDI) techniques. Disclosed MAI systems and methods may integrate image data in the z direction as the data are acquired, projecting the image data prior to deconvolution. Lateral translation of the image plane during the scan in the z direction may allow large areas to be imaged in a single scan sequence.
摘要翻译：使用多轴积分（MAI）的图像采集系统和方法可以并入光轴积分（OAI）和时延整合（TDI）技术。所公开的MAI系统和方法可以在采集数据时在z方向上集成图像数据，在去卷积之前投影图像数据。在z方向扫描期间的图像平面的横向平移可允许以单个扫描序列成像大面积。

8. 发明授权

US08237786B2 System and method for dense-stochastic-sampling imaging 有权
标题翻译：密集随机抽样成像的系统和方法
公开(公告)号：US08237786B2
公开(公告)日：2012-08-07
申请号：US12751816
申请日：2010-03-31
申请人： Gaudenz Danuser , Paul C. Goodwin
发明人： Gaudenz Danuser , Paul C. Goodwin
IPC分类号： H04N9/47 , H04N13/04
CPC分类号： G01N21/6428 , G01N21/636 , G01N21/6458 , G01N2021/6415 , G01N2021/6419 , G01N2201/126 , G02B21/365 , G02B21/367 , G06T3/4053
摘要： Embodiments of the present invention are directed to imaging technologies, and, in particular, to an imaging system that detects relatively weak signals, over time, and that uses the detected signals to determine the positions of signal emitters. Particular embodiments of the present invention are directed to methods and systems for imaging fluorophore-labeled samples in order to produce images of the sample at resolutions significantly greater than the diffraction-limited resolution associated with optical microscopy. Embodiments of the present invention employ overlapping-emitter-image disambiguation to allow data to be collected from densely arranged emitters, which significantly decreases the data-collection time for producing intermediate images as well as the number of intermediate images needed to computationally construct high-resolution final images. Additional embodiments of the present invention employ hierarchical image-processing techniques to further resolve and interpret disambiguated images.
摘要翻译：本发明的实施例涉及成像技术，特别涉及一种随时间检测相对较弱信号的成像系统，并且使用所检测的信号来确定信号发射器的位置。本发明的具体实施方案涉及用于成像荧光团标记的样品的方法和系统，以便以明显大于与光学显微镜相关联的衍射限制分辨率的分辨率产生样品的图像。本发明的实施例采用重叠 - 发射 - 图像消歧以允许从密集布置的发射器收集数据，这显着减少用于产生中间图像的数据收集时间以及计算构建高分辨率所需的中间图像的数量最终图像。本发明的另外的实施例采用分层图像处理技术来进一步解析和解释消歧图像。

9. 发明授权

US07408176B2 System and method employing photokinetic techniques in cell biology imaging applications 有权
标题翻译：在细胞生物学成像应用中使用光动力学技术的系统和方法
公开(公告)号：US07408176B2
公开(公告)日：2008-08-05
申请号：US10872329
申请日：2004-06-18
申请人： Paul C. Goodwin , Carl S. Brown , Steven A. Reese
发明人： Paul C. Goodwin , Carl S. Brown , Steven A. Reese
IPC分类号： G01N21/64
CPC分类号： G01N33/582 , G01N15/1475 , G01N21/6428 , G01N21/6452 , G01N21/6458 , G01N33/5005 , G06T5/003 , G06T2207/10064 , G06T2207/30024
摘要： A system and method employing photokinetic techniques in cell biology imaging applications are disclosed. Systems and methods of acquiring image data of an object may comprise: selectively inducing photoactivation of material at a site on the object; performing an optical axis integration scan; simultaneously executing a time delay integration scan sequence; and processing acquired image data in accordance with one or more desired analyses. Various methodologies and applications may include, inter alia, selective photobleaching of a site on the object, diffusion rate, velocity, and wave-front propagation analyses, multi-dimensional analyses of dispersion characteristics, biomolecular binding in cellular organelles, and photoactivation assisted systematic image segmentation for the study of cellular components.
摘要翻译：公开了在细胞生物学成像应用中使用光动力学技术的系统和方法。获取对象的图像数据的系统和方法可以包括：选择性地诱导物体上的物体的材料的光活化; 执行光轴积分扫描; 同时执行时间延迟积分扫描序列; 以及根据一个或多个期望的分析处理获取的图像数据。各种方法和应用可以包括对物体上的位点的选择性漂白，扩散速率，速度和波前传播分析，分散特征的多维分析，细胞器中的生物分子结合和光激活辅助系统图像细胞分析研究的细分。

10. 发明授权

US06862363B2 Image metrics in the statistical analysis of DNA microarray data 有权
标题翻译： DNA微阵列数据统计分析中的图像度量
公开(公告)号：US06862363B2
公开(公告)日：2005-03-01
申请号：US09770833
申请日：2001-01-25
申请人： Carl S. Brown , Paul C. Goodwin
发明人： Carl S. Brown , Paul C. Goodwin
IPC分类号： G01N33/53 , G01N37/00 , G06K9/00
CPC分类号： G06K9/00 , G06T7/0012 , G06T7/41 , G06T2207/30072
摘要： Expression profiling using DNA microarrays is an important new method for analyzing cellular physiology. In “spotted” microarrays, fluorescently labeled cDNA from experimental and control cells is hybridized to arrayed target DNA and the arrays imaged at two or more wavelengths. Statistical analysis is performed on microarray images and show that non-additive background, high intensity fluctuations across spots, and fabrication artifacts interfere with the accurate determination of intensity information. The probability density distributions generated by pixel-by-pixel analysis of images can be used to measure the precision with which spot intensities are determined. Simple weighting schemes based on these probability distributions are effective in improving significantly the quality of microarray data as it accumulates in a multi-experiment database. Error estimates from image-based metrics should be one component in an explicitly probabilistic scheme for the analysis of DNA microarray data.
摘要翻译：使用DNA微阵列进行表达谱分析是分析细胞生理学的重要新方法。在“斑点”微阵列中，来自实验和对照细胞的荧光标记的cDNA与排列的靶DNA杂交，并且阵列以两个或更多个波长成像。在微阵列图像上进行统计分析，并显示非加性背景，斑点高强度波动和制造伪影干扰强度信息的准确测定。通过像素逐像素分析图像生成的概率密度分布可用于测量确定斑点强度的精度。基于这些概率分布的简单加权方案在微阵列数据在多实验数据库中累积时的质量显着提高是有效的。基于图像的指标的误差估计应该是用于分析DNA微阵列数据的明确概率方案中的一个组成部分。

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