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1. 发明申请

WO2011136857A3 CORRELATION CONFOCAL MICROSCOPE 审中-公开
标题翻译：相关共形显微镜
公开(公告)号：WO2011136857A3
公开(公告)日：2011-12-22
申请号：PCT/US2011020186
申请日：2011-01-05
申请人： UNIV BOSTON , SIMON DAVID , SERGIENKO ALEXANDER , GOLDSTEIN LEE EDWIN , WEBB ROBERT H
发明人： SIMON DAVID , SERGIENKO ALEXANDER , GOLDSTEIN LEE EDWIN , WEBB ROBERT H
IPC分类号： G02B21/00 , G01B9/04
CPC分类号： G02B21/0004 , G02B21/0056 , G02B21/0084
摘要： A correlation confocal microscope uses correlated photon pairs to improve resolution. It employs a source of a light beam converging to a point location on a sample, and an objective that gathers light from the point location and generates an image beam. A modulator applies a spatial pattern of modulation to the source light beam to define spatially correlated photons whose spatial correlations are preserved in modulated light gathered from the sample. A filter applies a modulation-selective filter function to the image light beam to generate a filtered light beam of like-modulated photons. A coincidence detector detects temporally coincident photon pairs in the filtered light beam, generating a pulse output that indicates the magnitude of a light-detectable property (such as transmissivity or reflectivity) of the sample at the point location. The modulator may apply phase modulation and the filter may be a phase-sensitive component such as an interferometer.
摘要翻译：相关共焦显微镜使用相关光子对来提高分辨率。它采用聚焦到样本上点位置的光束源，以及从点位置聚集光线并生成图像光束的物镜。调制器将调制的空间模式应用于源光束以定义空间相关的光子，其空间相关性保存在从样品收集的调制光中。滤波器对图像光束应用调制选择性滤波功能以生成类似调制光子的滤波光束。重合检测器检测经滤波的光束中时间上重合的光子对，产生指示样点在点位置处的光可检测特性（诸如透射率或反射率）的大小的脉冲输出。调制器可以应用相位调制，并且滤波器可以是相位敏感的组件，例如干涉仪。

2. 发明申请

WO2008005402A2 DEVICE AND METHOD FOR WIDE- FIELD AND HIGH RESOLUTION IMAGING OF TISSUE 审中-公开
标题翻译：用于组织的大面积和高分辨率成像的装置和方法
公开(公告)号：WO2008005402A2
公开(公告)日：2008-01-10
申请号：PCT/US2007/015277
申请日：2007-06-29
申请人： THE GENERAL HOSPITAL CORPORATION , YAROSLAVSKY, Anna, M. , WEBB, Robert, H. , ANDERSON, Richard, Rox
发明人： YAROSLAVSKY, Anna, M. , WEBB, Robert, H. , ANDERSON, Richard, Rox
IPC分类号： G02B21/18
CPC分类号： G02B21/0024 , A61B5/0068 , A61B5/0071 , A61B5/444
摘要： A device for wide-field and high resolution imaging of an object surface includes first and second imaging modalities, a lens associated with the second imaging modality. The first imaging modality has a high resolution imaging means with a first observation line. The second imaging modality is arranged in an image plane at a first angle with respect to an object plane and has a second observation line and a wider imaging field than the first imaging modality. The lens associated with the second imaging modality is arranged in a lens plane at a second angle with respect to the object plane, where the second angle being equal to about one-half of the first angle. The first and second imaging modalities are mutually arranged such that the first and second optical axes intersect at a point on the object plane.
摘要翻译：用于物体表面的广域和高分辨率成像的装置包括第一和第二成像模态，与第二成像模态相关联的透镜。第一成像模式具有具有第一观察线的高分辨率成像装置。第二成像模式相对于物体平面以第一角度布置在图像平面中，并且具有比第一成像模态更多的第二观察线和更宽的成像场。与第二成像模态相关联的透镜相对于物平面以第二角度布置在透镜平面中，其中第二角度等于第一角度的大约二分之一。第一和第二成像模式被相互布置，使得第一和第二光轴在物平面上的点处相交。

3. 发明申请

WO2004017374A2 READING OF FLUORESCENT ARRAYS 审中-公开
标题翻译：读出荧光阵列
公开(公告)号：WO2004017374A2
公开(公告)日：2004-02-26
申请号：PCT/US2003/025702
申请日：2003-08-18
申请人： CLINICAL MICROARRAYS, INC. , MONTAGU, Jean, I. , WEBB, Robert, H.
发明人： MONTAGU, Jean, I. , WEBB, Robert, H.
IPC分类号： H01L
CPC分类号： G01N21/6452 , B01J2219/00315 , B01J2219/00387 , B01J2219/00533 , B01J2219/00605 , B01J2219/00612 , B01J2219/00637 , B01J2219/00641 , B01J2219/00722 , B01J2219/00725 , B01J2219/0074 , C40B40/06 , C40B40/10 , C40B60/14 , G01N21/274 , G01N21/6428 , G01N21/6456 , G01N33/54393 , G01N33/582
摘要： Reading of fluorescent arrays (103) in clinical settings is made possible by a reader (110) constructed to employ dark field illumination of the array, and mapping an image of the array onto a solid state sensor array (146) with image dimensions (D;) of the same order magnitude as the dimensions (D() of the fluorescent array, preferably with reduction of image. High intensity illumination is employed, non uniformities of which being compensated by normalization employing intensity calibration features (164) in the array itself, that are sensed during imaging of the array. Preferably high intensity light emitting diodes (122, 132, 402, 404), such as used in traffic lights, are employed for excitation of the array, preferably the excitation being introduced to the array via a solid internally reflecting homogenizer (130). Intermediate depth of field collection and imaging optics enable substantial collection of light, with NA in the range of 0.30 to 0.60, preferably in the range of 0.4 to 0.55. The resultant relatively large depth of field is in some advantageous cases compensated by absorbing light that tends to travel beyond the spots being imaged and would otherwise create noise fluorescence, the absorption produced e.g., by an opaque metal oxide coating (304) that is interposed between a substrate (302), preferably an ultra-thin substrate, on which the array lies, and the much thicker glass or other rigid support (306). For clinical purposes the arrays comprise fewer than 1000 spots, as is appropriate for protein, one example being an array of fewer than 500 spots. Relatively large spot sizes are employed, i.e. of the order of at least 80 or 100 micron diameter spots or preferably larger, 150 or 300 micron spots. Resolution of such spots to at least 50 pixels on the solid state detector array enables suitable binning and other manipulations leading to highly accurate results. Novel methods of assays and diagnosis such as cancer diagnosis employ the reader in detecting a set of markers related to the disease, for instance ovarian cancer.
摘要翻译：临床设置中的荧光阵列（103）的读取可以由构造为采用阵列的暗场照明的读取器（110）进行，并且将阵列的图像映射到具有图像尺寸（D）的固态传感器阵列（146）上）与荧光阵列的尺寸（D（））相同的数量级，优选地具有图像的降低。采用高强度照明，其非均匀性通过使用阵列本身中的强度校准特征（164）的归一化来补偿优选地，在交通灯中使用的高强度发光二极管（122,132,402,404）用于激励阵列，优选地，激励被引入阵列通过内部反射均匀器（130），中间景深采集和成像光学元件可实现大量的光收集，其中NA在0.30至0.60的范围内，优选在0.4 t o 0.55。所产生的相对较大的景深在一些有利的情况下通过吸收倾向于超过被成像的斑点的光而被补偿，否则将产生噪声荧光，例如通过不透明的金属氧化物涂层（304）产生的吸收，所述不透明金属氧化物涂层阵列所在的衬底（302），优选地是超薄衬底，以及更厚的玻璃或其它刚性支撑件（306）。对于临床目的，阵列包含少于1000个点，如适用于蛋白质，一个实例是少于500个点的阵列。使用相对较大的光斑尺寸，即大约至少80或100微米直径的斑点或优选较大的150或300微米光点。在固态检测器阵列上将这样的斑点分辨率至少为50像素使得能够进行合适的合并和其他操作，从而获得高度准确的结果。新的测定和诊断方法如癌症诊断使用读者检测与疾病相关的一组标志物，例如卵巢癌。

4. 发明申请

WO2008005402A3 DEVICE AND METHOD FOR WIDE- FIELD AND HIGH RESOLUTION IMAGING OF TISSUE 审中-公开
标题翻译：用于组织的宽场和高分辨率成像的装置和方法
公开(公告)号：WO2008005402A3
公开(公告)日：2008-04-10
申请号：PCT/US2007015277
申请日：2007-06-29
申请人： GEN HOSPITAL CORP , YAROSLAVSKY ANNA M , WEBB ROBERT H , ANDERSON RICHARD ROX
发明人： YAROSLAVSKY ANNA N , WEBB ROBERT H , ANDERSON RICHARD ROX
IPC分类号： A61B8/14
CPC分类号： G02B21/0024 , A61B5/0068 , A61B5/0071 , A61B5/444
摘要： A device for wide-field and high resolution imaging of an object surface includes first and second imaging modalities, a lens associated with the second imaging modality. The first imaging modality has a high resolution imaging means with a first observation line. The second imaging modality is arranged in an image plane at a first angle with respect to an object plane and has a second observation line and a wider imaging field than the first imaging modality. The lens associated with the second imaging modality is arranged in a lens plane at a second angle with respect to the object plane, where the second angle being equal to about one-half of the first angle. The first and second imaging modalities are mutually arranged such that the first and second optical axes intersect at a point on the object plane.
摘要翻译：一种用于对象表面的宽视野和高分辨率成像的设备包括第一成像模态和第二成像模态，与第二成像模态相关联的透镜。第一成像模式具有带有第一观察线的高分辨率成像装置。第二成像模态相对于物平面以第一角度布置在像平面中，并且具有比第一成像模态更宽的第二观察线和更宽的成像场。与第二成像模态相关联的透镜相对于物平面以第二角度布置在透镜平面中，其中第二角度等于第一角度的大约一半。第一成像模态和第二成像模态被相互布置为使得第一光轴和第二光轴在物平面上的点处相交。

5. 发明申请

WO2011136857A2 CORRELATION CONFOCAL MICROSCOPE 审中-公开
标题翻译：相关协同显微镜
公开(公告)号：WO2011136857A2
公开(公告)日：2011-11-03
申请号：PCT/US2011/020186
申请日：2011-01-05
申请人： TRUSTEES OF BOSTON UNIVERSITY , SIMON, David , SERGIENKO, Alexander , GOLDSTEIN, Lee, Edwin , WEBB, Robert, H.
发明人： SIMON, David , SERGIENKO, Alexander , GOLDSTEIN, Lee, Edwin , WEBB, Robert, H.
IPC分类号： G02B21/00 , G01B9/04
CPC分类号： G02B21/0004 , G02B21/0056 , G02B21/0084
摘要： A correlation confocal microscope uses correlated photon pairs to improve resolution. It employs a source of a light beam converging to a point location on a sample, and an objective that gathers light from the point location and generates an image beam. A modulator applies a spatial pattern of modulation to the source light beam to define spatially correlated photons whose spatial correlations are preserved in modulated light gathered from the sample. A filter applies a modulation-selective filter function to the image light beam to generate a filtered light beam of like-modulated photons. A coincidence detector detects temporally coincident photon pairs in the filtered light beam, generating a pulse output that indicates the magnitude of a light-detectable property (such as transmissivity or reflectivity) of the sample at the point location. The modulator may apply phase modulation and the filter may be a phase-sensitive component such as an interferometer.
摘要翻译：相关共焦显微镜使用相关的光子对来提高分辨率。它采用会聚到样本上的点位置的光束源，以及从点位置收集光并产生图像束的目标。调制器将调制空间模式应用于源光束以限定空间相关光子，其空间相关性保留在从样本收集的调制光中。滤波器将调制选择滤波器功能应用于图像光束以产生经过调制的光子的滤波光束。符合检测器检测滤波光束中的时间上重合的光子对，产生指示样品在点位置处的可光可检测特性（例如透射率或反射率）的幅度的脉冲输出。调制器可以进行相位调制，并且滤波器可以是诸如干涉仪之类的相敏元件。

6. 发明申请

WO2004017374A3 READING OF FLUORESCENT ARRAYS 审中-公开
标题翻译：读取荧光阵列
公开(公告)号：WO2004017374A3
公开(公告)日：2004-06-10
申请号：PCT/US0325702
申请日：2003-08-18
申请人： CLINICAL MICROARRAYS INC , MONTAGU JEAN I , WEBB ROBERT H
发明人： MONTAGU JEAN I , WEBB ROBERT H
IPC分类号： G01N1/28 , C40B40/06 , C40B40/10 , C40B60/14 , G01N21/64 , G01N33/58 , G01N37/00 , G01N33/543
CPC分类号： G01N21/6452 , B01J2219/00315 , B01J2219/00387 , B01J2219/00533 , B01J2219/00605 , B01J2219/00612 , B01J2219/00637 , B01J2219/00641 , B01J2219/00722 , B01J2219/00725 , B01J2219/0074 , C40B40/06 , C40B40/10 , C40B60/14 , G01N21/274 , G01N21/6428 , G01N21/6456 , G01N33/54393 , G01N33/582
摘要： An array reader suitable for clinical purposes for reading a two-dimensional array of photo-responsive markers on a planar substrate that are capable of emitting light upon excitation. The reader is constructed to employ dark field illumination as well as high intensity illumination. High intensity light emitting diodes are preferrably employed for the excitation of the array via a solid internally reflecting homogenizer. Intermediate depth of field collection and imaging optics enable substantial collection of light, with NA in the range of 0.30 to 0.60.
摘要翻译：适用于临床目的的阵列读取器，用于读取能够在激发时发光的平面基板上的光响应标记的二维阵列。读者构造为采用暗场照明以及高强度照明。高强度发光二极管优选用于通过固体内反射均化器激发阵列。中间景深采集和成像光学元件能够实现大量的光的收集，NA在0.30至0.60的范围内。

7. 发明申请

WO03046636A9 CONFOCAL MICROSCOPY WITH MULTI-SPECTRAL ENCODING AND SYSTEM AND APPARATUS FOR SPECTROSCOPICALLY ENCODED CONFOCAL MICROSCOPY 审中-公开
标题翻译：具有多光谱编码和系统的共焦显微镜和用于光谱编码的共焦显微镜的装置
公开(公告)号：WO03046636A9
公开(公告)日：2004-02-26
申请号：PCT/US0238335
申请日：2002-11-27
申请人： GEN HOSPITAL CORP , TEARNEY GUILLERMO J , BOUMA BRETT E , WEBB ROBERT H , PITRIS CONSTANTINOS , SHISHKOV MILLEN
发明人： TEARNEY GUILLERMO J , BOUMA BRETT E , WEBB ROBERT H , PITRIS CONSTANTINOS , SHISHKOV MILLEN
IPC分类号： A61B1/00 , A61B1/07 , A61B5/00 , A61B10/00 , A61B19/00 , G01J3/28 , G02B21/00 , G02B21/18 , G02B21/36 , G02B23/24 , G02B21/06
CPC分类号： A61B1/00096 , A61B1/00172 , A61B5/0068 , A61B5/0075 , A61B5/0084 , A61B5/415 , A61B5/418 , A61B5/6852 , G01J3/02 , G01J3/0208 , G01J3/0218 , G01J3/0291 , G01J3/06 , G01J3/12 , G01J3/14 , G01J3/18 , G01J3/28 , G01J2003/062 , G01J2003/064 , G01J2003/065 , G01J2003/069 , G02B21/0028 , G02B21/0056 , G02B21/0064 , G02B21/0076 , G02B23/2453
摘要： A scanning confocal microscopy system and apparatus, especially useful for endoscopy with a flexible probe which is connected to the end of an optical fiber (9). The probe has a grating (12) and a lens (14) which delivers a beam of multi-spectral light having spectral components which extend in one dimension across a region of an object and which is moved to scan in another dimension. The reflected confocal spectrum is measured to provide an image of the region.
摘要翻译：一种扫描共焦显微镜系统和装置，其特别适用于连接到光纤端部（9）的柔性探头的内窥镜检查。探针具有光栅（12）和透镜（14），其传送具有光谱分量的多光谱光束，该光谱分量在一个维度上跨过物体的区域延伸并且被移动以在另一维度上扫描。测量反射共焦光谱以提供该区域的图像。

8. 发明申请

WO03011122A3 IMAGING APPARATUS AND METHODS FOR NEAR SIMULTANEOUS OBSERVATION OF DIRECTLY SCATTERED LIGHT AND MULTIPLY SCATTERED LIGHT 审中-公开
标题翻译：近距离观察直角光和多光散射光的成像装置及方法
公开(公告)号：WO03011122A3
公开(公告)日：2003-07-10
申请号：PCT/US0224254
申请日：2002-07-31
申请人： SCHEPENS EYE RES INST , ELSNER ANN E , BURNS STEPHEN A , DREHER ANDREAS W , WEBB ROBERT H
发明人： ELSNER ANN E , BURNS STEPHEN A , DREHER ANDREAS W , WEBB ROBERT H
IPC分类号： A61B3/12 , G01N21/47 , G02B27/10
CPC分类号： A61B3/12 , G01N21/4795
摘要： An apparatus and a method are disclosed for separating light remitted by a target into a directly scattered light component and at least one multiply scattered light component, detecting the components at least substantially simultaneously, and forming independent sets of image information from each component. The apparatus and the method can be employed in conjunction with techniques such as scanning and tomograghy to attain precise imaging of biological tissue, including the retina of the eye.
摘要翻译：公开了一种用于将由目标滤波的光分离为直接散射光分量和至少一个多重散射光分量的装置和方法，用于至少基本上同时地检测所述分量，并从每个分量形成独立的图像信息集。该装置和方法可以与诸如扫描和断层扫描技术结合使用，以获得包括眼睛视网膜在内的生物组织的精确成像。

9. 发明申请

WO2003046636A1 CONFOCAL MICROSCOPY WITH MULTI-SPECTRAL ENCODING AND SYSTEM AND APPARATUS FOR SPECTROSCOPICALLY ENCODED CONFOCAL MICROSCOPY 审中-公开
标题翻译：具有多光谱编码和系统的共焦显微镜和用于光谱编码的共焦显微镜的装置
公开(公告)号：WO2003046636A1
公开(公告)日：2003-06-05
申请号：PCT/US2002/038335
申请日：2002-11-27
申请人： THE GENERAL HOSPITAL CORPORATION , TEARNEY, Guillermo, J. , BOUMA, Brett, E. , WEBB, Robert, H. , PITRIS, Constantinos , SHISHKOV, Millen
发明人： TEARNEY, Guillermo, J. , BOUMA, Brett, E. , WEBB, Robert, H. , PITRIS, Constantinos , SHISHKOV, Millen
IPC分类号： G02B21/06
CPC分类号： A61B1/00096 , A61B1/00172 , A61B5/0068 , A61B5/0075 , A61B5/0084 , A61B5/415 , A61B5/418 , A61B5/6852 , G01J3/02 , G01J3/0208 , G01J3/0218 , G01J3/0291 , G01J3/06 , G01J3/12 , G01J3/14 , G01J3/18 , G01J3/28 , G01J2003/062 , G01J2003/064 , G01J2003/065 , G01J2003/069 , G02B21/0028 , G02B21/0056 , G02B21/0064 , G02B21/0076 , G02B23/2453
摘要： A scanning confocal microscopy system and apparatus, especially useful for endoscopy with a flexible probe which is connected to the end of an optical fiber (9). The probe has a grating (12) and a lens (14) which delivers a beam of multi-spectral light having spectral components which extend in one dimension across a region of an object and which is moved to scan in another dimension. The reflected confocal spectrum is measured to provide an image of the region.
摘要翻译：一种扫描共聚焦显微镜系统和装置，特别适用于连接到光纤端部（9）的柔性探头的内窥镜检查。探针具有光栅（12）和透镜（14），其传送具有光谱分量的多光谱光束，该光谱分量在一个维度上延伸跨越物体的区域并且被移动以在另一维度上扫描。测量反射共焦光谱以提供该区域的图像。

10. 发明申请

WO2003011122A2 IMAGING APPARATUS AND METHODS FOR NEAR SIMULTANEOUS OBSERVATION OF DIRECTLY SCATTERED LIGHT AND MULTIPLY SCATTERED LIGHT 审中-公开
标题翻译：用于近似同时观察直接散射光和多散射光的成像装置和方法
公开(公告)号：WO2003011122A2
公开(公告)日：2003-02-13
申请号：PCT/US2002/024254
申请日：2002-07-31
申请人： THE SCHEPENS EYE RESEARCH INSTITUTE , ELSNER, Ann, E. , BURNS, Stephen, A. , DREHER, Andreas, W. , WEBB, Robert, H.
发明人： ELSNER, Ann, E. , BURNS, Stephen, A. , DREHER, Andreas, W. , WEBB, Robert, H.
IPC分类号： A61B3/12
CPC分类号： A61B3/12 , G01N21/4795
摘要： An apparatus and a method are disclosed for separating light remitted by a target into a directly scattered light component and at least one multiply scattered light component, detecting the components at least substantially simultaneously, and forming independent sets of image information from each component. The apparatus and the method can be employed in conjunction with techniques such as scanning and tomograghy to attain precise imaging of biological tissue, including the retina of the eye.
摘要翻译：公开了一种装置和方法，用于将由目标减光的光分成直接散射光分量和至少一个多散射光分量，至少基本上同时检测这些分量，并形成独立的来自每个组件的图像信息。该装置和方法可以与诸如扫描和断层扫描的技术结合使用，以实现生物组织的精确成像，包括眼睛的视网膜。

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