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1. 发明授权

US5321501A Method and apparatus for optical imaging with means for controlling the longitudinal range of the sample 失效
标题翻译：用于光学成像的方法和装置，其具有用于控制样品的纵向范围的装置
公开(公告)号：US5321501A
公开(公告)日：1994-06-14
申请号：US875670
申请日：1992-04-29
申请人： Eric A. Swanson , David Huang , James G. Fujimoto , Carmen A. Puliafito , Charles P. Lin , Joel S. Schuman
发明人： Eric A. Swanson , David Huang , James G. Fujimoto , Carmen A. Puliafito , Charles P. Lin , Joel S. Schuman
IPC分类号： A61B1/00 , A61B3/10 , A61B3/12 , A61B5/00 , A61B5/103 , A61B10/00 , G01B9/02 , G01B11/00 , G01B11/06 , G01B11/24 , G01J1/00 , G01N21/17 , G01N21/47 , G02B5/18 , G02B27/44 , G11B7/00 , H01S5/14
CPC分类号： G02B26/0875 , A61B1/00096 , A61B1/00172 , A61B1/00183 , A61B3/102 , A61B5/0064 , A61B5/0066 , A61B5/0068 , A61B5/0084 , A61B5/6852 , B82Y15/00 , G01B11/00 , G01B11/2441 , G01B9/02002 , G01B9/0201 , G01B9/02019 , G01B9/02027 , G01B9/02063 , G01B9/02087 , G01B9/0209 , G01J1/00 , G01N21/4795 , G02B26/103 , G02B5/1828 , A61B2562/0242 , A61B5/441 , G01B2290/45 , G01B2290/65 , G01B2290/70 , G11B2007/0013 , H01S5/141
摘要： A method and apparatus for performing optical imaging on a sample wherein longitudinal scanning or positioning in the sample is provided by either varying relative optical path lengths for an optical path leading to the sample and to a reference reflector, or by varying an optical characteristic of the output from an optical source applied to the apparatus. Transverse scanning in one or two dimensions is provided on the sample by providing controlled relative movement between the sample and a probe module in such direction and/or by steering optical radiation in the probe module to a selected transverse position. The probe module may be an external module or may be an endoscope or angioscope utilized for scanning internal channels. Multiple optical paths may be provided for parallel scanning and focus may be enhanced by varying the focal point in the sample in synchronism with longitudinal scanning of the sample.
摘要翻译：或者通过对通过样品和参考反射体的光路改变相对光程长度，或者通过改变样品的光学特性来改变样品中的纵向扫描或定位来提供样品的光学成像的方法和装置从施加到该装置的光源输出。通过在样品和探针模块之间以这种方向提供受控的相对运动和/或通过将探针模块中的光学辐射转向到选定的横向位置，在样品上提供一维或二维的横向扫描。探针模块可以是外部模块，也可以是用于扫描内部通道的内窥镜或血管造影仪。可以提供用于并行扫描的多个光路，并且可以通过与样品的纵向扫描同步地改变样品中的焦点来增强焦点。

2. 发明授权

US5459570A Method and apparatus for performing optical measurements 失效
标题翻译：用于执行光学测量的方法和装置
公开(公告)号：US5459570A
公开(公告)日：1995-10-17
申请号：US33194
申请日：1993-03-16
申请人： Eric A. Swanson , David Huang , James G. Fujimoto , Carmen A. Puliafito , Charles P. Lin , Joseph S. Schuman
发明人： Eric A. Swanson , David Huang , James G. Fujimoto , Carmen A. Puliafito , Charles P. Lin , Joseph S. Schuman
IPC分类号： A61B1/00 , A61B3/10 , A61B3/12 , A61B5/00 , A61B5/103 , A61B10/00 , G01B9/02 , G01B11/00 , G01B11/06 , G01B11/24 , G01J1/00 , G01N21/17 , G01N21/47 , G02B5/18 , G02B27/44 , G11B7/00 , H01S5/14 , G01D9/02
CPC分类号： G02B26/0875 , A61B1/00096 , A61B1/00172 , A61B1/00183 , A61B3/102 , A61B5/0064 , A61B5/0066 , A61B5/0068 , A61B5/0084 , A61B5/6852 , B82Y15/00 , G01B11/00 , G01B11/2441 , G01B9/02002 , G01B9/0201 , G01B9/02019 , G01B9/02027 , G01B9/02063 , G01B9/02087 , G01B9/0209 , G01J1/00 , G01N21/4795 , G02B26/103 , G02B5/1828 , A61B2562/0242 , A61B5/441 , G01B2290/45 , G01B2290/65 , G01B2290/70 , G11B2007/0013 , H01S5/141
摘要： A method and apparatus for performing various optical measurements is provided utilizing an optical coherence domain refrectometer (OCDR). A short coherence optical radiation source applies optical radiation through like optical paths to a sample and an optical reflector. The optical reflector is movable in accordance with a predetermined velocity profile to permit interferometric scanning of the sample, the resulting output having a Doppler shift frequency modulation. This output may be demodulated and detected to obtain desired measurements and other information. Additional information may be obtained by applying radiation from two or more sources at different wavelengths to the sample and reflector and by separately demodulating the resulting outputs before processing. Birefringent information may be obtained by polarizing the optical radiation used, by suitably modifying the polarization in the sample and reference paths and by dividing the output into orthogonal polarization outputs which are separately demodulated before processing.
摘要翻译：使用光学相干域反射计（OCDR）提供用于执行各种光学测量的方法和装置。短相干光辐射源通过相同的光路将光辐射施加到样品和光反射器。光学反射器可以根据预定的速度分布移动以允许样本的干涉扫描，所得到的输出具有多普勒频移调制。该输出可以被解调和检测以获得期望的测量和其他信息。可以通过将不同波长的两个或更多个源的辐射施加到样品和反射器并且在处理之前单独解调所得到的输出来获得附加信息。双折射信息可以通过对所采用的光辐射进行极化，通过适当地修改样本和参考路径中的极化，并将输出划分为在处理之前被单独解调的正交偏振输出。

3. 发明授权

US08968280B2 Dose determination for inducing microcavitation in retinal pigment epithelium (RPE) 有权
标题翻译：用于诱导视网膜色素上皮（RPE）微量化的剂量测定
公开(公告)号：US08968280B2
公开(公告)日：2015-03-03
申请号：US13145605
申请日：2010-01-22
申请人： Charles P. Lin , Clemens Alt , Ho Lee
发明人： Charles P. Lin , Clemens Alt , Ho Lee
IPC分类号： A61B18/18 , A61F9/008
CPC分类号： A61F9/008 , A61F9/00821 , A61F2009/00863
摘要： Methods and systems for controlling selective targeting of retinal pigment epithelium (RPE) cells within a treatment region of the RPE. The methods include (a) depositing a selected amount of energy on a test region of the RPE; (b) determining an extent to which microcavitation has occurred in the test region; and (c) on the basis of the determination, either depositing the selected amount of energy on the treatment region, or depositing an increased amount of energy on the test region, and repeating steps (b) and (c).
摘要翻译：用于控制RPE治疗区域内视网膜色素上皮细胞（RPE）细胞选择性靶向的方法和系统。所述方法包括（a）在RPE的测试区域上沉积选定量的能量; （b）确定在测试区域发生微气蚀的程度; 和（c）基于该确定，将所选择的能量沉积在处理区域上，或者在测试区域上沉积增加的能量，并重复步骤（b）和（c）。

4. 发明授权

US08574859B2 In vivo flow cytometry based on cellular autofluorescence 有权
标题翻译：基于细胞自体荧光的体内流式细胞术
公开(公告)号：US08574859B2
公开(公告)日：2013-11-05
申请号：US12867141
申请日：2009-03-27
申请人： Charles P. Lin , Alicia L. Carlson , Clemens Alt , David P. Biss , Costas M. Pitsillides , Chunqiang Li
发明人： Charles P. Lin , Alicia L. Carlson , Clemens Alt , David P. Biss , Costas M. Pitsillides , Chunqiang Li
IPC分类号： G01N33/00
CPC分类号： A61B5/0071 , A61B5/0059 , A61B5/0068 , G01N15/1434 , G01N33/537 , G01N33/56972 , G01N2015/008 , G01N2015/1497 , Y10T436/13
摘要： The present invention generally provides methods and systems for performing in vivo flow cytometry by using blood vessels as flow chambers through which flowing cells can be monitored in a live subject in vivo without the need for withdrawing a blood sample. In some embodiments, one or more blood vessels are illuminated with radiation so as to cause a multi-photon excitation of an exogenous fluorophore that was previously introduced into the subject to label one or more cell types of interest. In some other embodiments, rather than utilizing an exogenous fluorophore, endogenous (intrinsic) cellular fluorescence can be employed for in vivo flow cytometry. The emission of fluorescence radiation from such fluorophores in response to the excitation can be detected and analyzed to obtain information regarding a cell type of interest.
摘要翻译：本发明通常提供了通过使用血管作为流动室进行体内流式细胞术的方法和系统，通过该流室可以在活体内体内监测流动细胞，而不需要抽出血样。在一些实施方案中，用辐射照射一个或多个血管，以便引起先前引入对象的外源性荧光团的多光子激发以标记一种或多种感兴趣的细胞类型。在一些其它实施方案中，不是利用外源荧光团，内源（内在）细胞荧光可用于体内流式细胞术。可以检测和分析来自这种荧光团的响应于激发的荧光辐射的发射以获得关于感兴趣的细胞类型的信息。

5. 发明授权

US07745155B2 In-vivo monitoring of circulating apoptotic cells 有权
标题翻译：循环凋亡细胞的体内监测
公开(公告)号：US07745155B2
公开(公告)日：2010-06-29
申请号：US11190729
申请日：2005-07-27
申请人： Charles P. Lin , Xunbin Wei , Dorothy Sipkins
发明人： Charles P. Lin , Xunbin Wei , Dorothy Sipkins
IPC分类号： G01N33/574 , G01N21/00 , G01N21/66 , A61K49/00
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0097 , G01N33/56966 , G01N33/57496 , G01N33/582 , G01N2510/00 , G01N2800/52 , Y10T436/101666 , Y10T436/13
摘要： The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in-vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest. In some embodiments, the circulating cells comprise apoptotic cells whose detection can allow, e.g., non-invasive monitoring of the efficacy of a cancer treatment, such as an anti-tumor or an anti-angiogenic therapy.
摘要翻译：本发明提供用于进行体内流式细胞术的方法和系统。在一个实施方案中，用荧光探针分子标记受试者感兴趣的选定的循环细胞。将标记的细胞体内照射以激发荧光探针，并且检测被激发的探针发射的辐射，优选共方。然后分析所检测的辐射以获得感兴趣的细胞的所需信息，例如相对细胞计数。在一些实施方案中，循环细胞包含凋亡细胞，其检测可以允许例如非侵入性监测癌症治疗（例如抗肿瘤或抗血管生成治疗）的功效。

6. 发明授权

US07292390B2 Fiber-coupled multiplexed confocal microscope 失效
标题翻译：光纤耦合多重共焦显微镜
公开(公告)号：US07292390B2
公开(公告)日：2007-11-06
申请号：US10830905
申请日：2004-04-22
申请人： Charles P. Lin , Robert H. Webb
发明人： Charles P. Lin , Robert H. Webb
IPC分类号： G02B21/06
CPC分类号： G02B21/0032 , G02B21/0024 , G02B21/0028
摘要： A confocal microscope system that is inherently fiberoptic compatible is described which has line scanning aided image formation. An incoherent fiberoptic bundle maps a line illumination pattern into a dispersible group of separate sources, and then remaps this confocally selected remitted light to the original line. Fibers, not confocal with the illumination, carry light to be rejected from the image back on itself upon double passing, while separate fibers carry light from non-confocal sample planes. The transformation allows efficient rejection of unwanted photons at a slit aperture. The fiber bundle and an objective lens provide a flexible probe for imaging internal tissue for pathological examination on a cellular level.
摘要翻译：描述了固有地光纤相容的共焦显微镜系统，其具有线扫描辅助图像形成。不相干的光纤束将线照明图案映射成可分散的一组源，然后将该共同选择的汇入光重新映射到原始行。不共焦照明的光纤在双重通过时将光从图像中反射回来，而分离的光纤携带非共焦样品平面的光。该转换允许在狭缝孔径处有效地排除不需要的光子。纤维束和物镜提供用于成像内部组织以在细胞水平进行病理检查的柔性探针。

7. 发明申请

US20110044910A1 IN VIVO FLOW CYTOMETRY BASED ON CELLULAR AUTOFLUORESCENCE 有权
标题翻译：基于细胞自动化的血液流式细胞仪检测
公开(公告)号：US20110044910A1
公开(公告)日：2011-02-24
申请号：US12867141
申请日：2009-03-27
申请人： Charles P. Lin , Alicia L. Carlson , Clemens Alt , David P. Biss , Costas M. Pitsillides , Chunqiang Li
发明人： Charles P. Lin , Alicia L. Carlson , Clemens Alt , David P. Biss , Costas M. Pitsillides , Chunqiang Li
IPC分类号： A61K49/00 , G01J1/58
CPC分类号： A61B5/0071 , A61B5/0059 , A61B5/0068 , G01N15/1434 , G01N33/537 , G01N33/56972 , G01N2015/008 , G01N2015/1497 , Y10T436/13
摘要： The present invention generally provides methods and systems for performing in vivo flow cytometry by using blood vessels as flow chambers through which flowing cells can be monitored in a live subject in vivo without the need for withdrawing a blood sample. In some embodiments, one or more blood vessels are illuminated with radiation so as to cause a multi-photon excitation of an exogenous fluorophore that was previously introduced into the subject to label one or more cell types of interest. In some other embodiments, rather than utilizing an exogenous fluorophore, endogenous (intrinsic) cellular fluorescence can be employed for in vivo flow cytometry. The emission of fluorescence radiation from such fluorophores in response to the excitation can be detected and analyzed to obtain information regarding a cell type of interest.
摘要翻译：本发明通常提供了通过使用血管作为流动室进行体内流式细胞术的方法和系统，通过该流室可以在活体内体内监测流动细胞，而不需要抽出血样。在一些实施方案中，用辐射照射一个或多个血管，以便引起先前引入对象的外源性荧光团的多光子激发以标记一种或多种感兴趣的细胞类型。在一些其它实施方案中，不是利用外源荧光团，内源（内在）细胞荧光可用于体内流式细胞术。可以检测和分析来自这种荧光团的响应于激发的荧光辐射的发射以获得关于感兴趣的细胞类型的信息。

8. 发明申请

US20100233092A1 IN-VIVO MONITORING OF CIRCULATING APOPTOTIC CELLS 有权
标题翻译：循环细胞的血管内监测
公开(公告)号：US20100233092A1
公开(公告)日：2010-09-16
申请号：US12785833
申请日：2010-05-24
申请人： Charles P. Lin , Xunbin Wei , Dorothy Sipkins
发明人： Charles P. Lin , Xunbin Wei , Dorothy Sipkins
IPC分类号： A61K49/00
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0097 , G01N33/56966 , G01N33/57496 , G01N33/582 , G01N2510/00 , G01N2800/52 , Y10T436/101666 , Y10T436/13
摘要： The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in-vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest. In some embodiments, the circulating cells comprise apoptotic cells whose detection can allow, e.g., non-invasive monitoring of the efficacy of a cancer treatment, such as an anti-tumor or an anti-angiogenic therapy.
摘要翻译：本发明提供用于进行体内流式细胞术的方法和系统。在一个实施方案中，用荧光探针分子标记受试者感兴趣的选定的循环细胞。将标记的细胞体内照射以激发荧光探针，并且检测被激发的探针发射的辐射，优选共方。然后分析所检测的辐射以获得感兴趣的细胞的所需信息，例如相对细胞计数。在一些实施方案中，循环细胞包含凋亡细胞，其检测可以允许例如非侵入性监测癌症治疗（例如抗肿瘤或抗血管生成治疗）的功效。

9. 发明申请

US20100049041A1 IN VIVO FLOW CYTOMETRY SYSTEM AND METHOD 有权
标题翻译：体内流式细胞仪系统和方法
公开(公告)号：US20100049041A1
公开(公告)日：2010-02-25
申请号：US12349612
申请日：2009-01-07
申请人： Charles P. Lin
发明人： Charles P. Lin
IPC分类号： A61B5/1455
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0097 , G01N33/56966 , G01N33/57496 , G01N33/582 , G01N2510/00 , G01N2800/52 , Y10T436/101666 , Y10T436/13
摘要： The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest.
摘要翻译：本发明提供用于进行体内流式细胞术的方法和系统。在一个实施方案中，用荧光探针分子标记受试者感兴趣的选定的循环细胞。在体内照射标记的细胞以激发荧光探针，并且检测被激发的探针发射的辐射，优选共方。然后分析所检测的辐射以获得感兴趣的细胞的所需信息，例如相对细胞计数。

10. 发明授权

US07491502B2 In vivo flow cytometry system and method 失效
标题翻译：体内流式细胞仪系统及方法
公开(公告)号：US07491502B2
公开(公告)日：2009-02-17
申请号：US11015334
申请日：2004-12-17
申请人： Charles P. Lin
发明人： Charles P. Lin
IPC分类号： G01N33/567
CPC分类号： A61K49/0032 , A61K49/0056 , A61K49/0097 , G01N33/56966 , G01N33/57496 , G01N33/582 , G01N2510/00 , G01N2800/52 , Y10T436/101666 , Y10T436/13
摘要： The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest.
摘要翻译：本发明提供用于进行体内流式细胞术的方法和系统。在一个实施方案中，用荧光探针分子标记受试者感兴趣的选定的循环细胞。在体内照射标记的细胞以激发荧光探针，并且检测被激发的探针发射的辐射，优选共方。然后分析所检测的辐射以获得感兴趣的细胞的所需信息，例如相对细胞计数。

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