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21. 发明授权

US07264794B2 Methods of in vivo cytometry 有权
标题翻译：体内细胞计数方法
公开(公告)号：US07264794B2
公开(公告)日：2007-09-04
申请号：US11016545
申请日：2004-12-17
申请人： Irene Georgakoudi , Charles P. Lin
发明人： Irene Georgakoudi , Charles P. Lin
IPC分类号： A61K49/00
CPC分类号： A61B5/1455 , A61B2503/40 , G01N15/1459 , G01N2015/0073 , G01N2015/008 , G01N2015/0084 , G01N2015/1486 , G01N2015/1488
摘要： The present invention provides methods and systems for performing in-vivo flow cytometry to obtain desired information regarding one or more cell types of interest flowing through a subject's circulatory system. In one embodiment of the invention, a portion of the subject's circulating blood is illuminated with radiation having multiple wavelength components, and the backscattered radiation generated in response to the excitation radiation is detected at a plurality of scattering angles and analyzed to derive the desired information.
摘要翻译：本发明提供用于进行体内流式细胞术以获得关于流过对象的循环系统的一种或多种感兴趣细胞类型的期望信息的方法和系统。在本发明的一个实施例中，用具有多个波长分量的辐射照射受试者的循环血液的一部分，并且以多个散射角度检测响应于激发辐射而产生的反向散射辐射并分析以导出所需信息。

22. 发明授权

US07115120B2 Selective photocoagulation 有权
标题翻译：选择性凝固
公开(公告)号：US07115120B2
公开(公告)日：2006-10-03
申请号：US10296417
申请日：2001-06-01
申请人： Charles P. Lin
发明人： Charles P. Lin
IPC分类号： A61B18/18
CPC分类号： A61B18/20 , A61B2017/00057 , A61B2018/00636 , A61B2018/00642 , A61F9/008 , A61F9/00821 , A61F2009/00844 , A61F2009/00855 , A61F2009/00863 , A61F2009/00897
摘要： Selective photocoagulation of particular cells, tissue or portion of tissue can be aided by monitoring microcavitation within the material exposed to electromagnetic radiation (12). The information gained by the detection of microcavitation events can be used to modulate the intensity of the radiation (12) to prevent significant thermal energy transmission and mechanical damage to cells, tissues or portions of tissues which are not directly exposed, but prone to thermal damage by such energy transmission. Detection of microcavitation also serves as a valuable therapeutic endpoint. The methods of the invention are applicable to laser eye surgery, since the target cells of several therapeutic photocoagulation methods, the retinal pigment epithelial (RPE) cells are proximate to photoreceptor cells. The inventive methods can help prevent the formation of blind spots that can be associated with laser eye surgery. Other fields of laser surgery can also be readily adapted to the methods described herein.
摘要翻译：可以通过监测暴露于电磁辐射的材料（12）中的微气蚀来辅助特定细胞，组织或组织部分的选择性光凝。通过检测微气泡事件获得的信息可用于调节辐射强度（12），以防止对细胞，组织或组织的显着的热能传递和机械损伤，这些组织或组织部分不直接暴露，但易受热损伤通过这种能量传递。微腔的检测也可作为有价值的治疗终点。本发明的方法适用于激光眼科手术，因为几种治疗性光凝方法的靶细胞，视网膜色素上皮（RPE）细胞接近感光细胞。本发明的方法可以帮助防止形成与激光眼科手术有关的盲点。激光手术的其他领域也可以容易地适应于本文所述的方法。

23. 发明授权

US06747795B2 Fiber-coupled multiplexed confocal microscope 失效
标题翻译：光纤耦合多重共聚焦显微镜
公开(公告)号：US06747795B2
公开(公告)日：2004-06-08
申请号：US09885576
申请日：2001-06-20
申请人： Charles P. Lin , Robert H. Webb
发明人： Charles P. Lin , Robert H. Webb
IPC分类号： G02B2106
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。

24. 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。

25. 发明授权

US09968259B2 Systems and methods for sensing, enumerating and imaging rare cells with diffuse light 有权
公开(公告)号：US09968259B2
公开(公告)日：2018-05-15
申请号：US14371850
申请日：2013-01-24
申请人： Mark Niedre , Eric William Zettergren , Charles P. Lin
发明人： Mark Niedre , Eric William Zettergren , Charles P. Lin
IPC分类号： A61B5/00 , G01N15/14
CPC分类号： A61B5/0071 , A61B5/0073 , G01N15/1404 , G01N15/1434 , G01N2015/1445
摘要： Diffuse fluorescence flow cytometers and methods of using them include a plurality of excitation sources and a plurality of detectors, all circumferentially arranged about a space for accommodating a limb of a subject. Tomographic reconstructions of cells within the limb are made by varying the intensity and direction of excitation and then analyzing the results.

26. 发明授权

US08211660B2 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：US08211660B2
公开(公告)日：2012-07-03
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： G01N33/574 , 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。

27. 发明授权

US08178342B2 In vivo flow cytometry system and method 有权
标题翻译：体内流式细胞仪系统及方法
公开(公告)号：US08178342B2
公开(公告)日：2012-05-15
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： C12M1/34
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。

28. 发明授权

US07790443B2 Bioreactors with substance injection capacity 有权
标题翻译：具有物质注入能力的生物反应器
公开(公告)号：US07790443B2
公开(公告)日：2010-09-07
申请号：US10525648
申请日：2003-08-27
申请人： John P. Wikswo , Franz J. Baudenbacher , Frederick R. Haselton , William H. Hofmeister , Charles P. Lin , Lisa J. McCawley , Mark A. Stremler , Alissa Weaver
发明人： John P. Wikswo , Franz J. Baudenbacher , Frederick R. Haselton , William H. Hofmeister , Charles P. Lin , Lisa J. McCawley , Mark A. Stremler , Alissa Weaver
IPC分类号： C12M1/00 , C12M3/00
CPC分类号： B01L3/502761 , B01L3/502723 , B01L3/502746 , B01L2200/0668 , B01L2300/0645 , B01L2300/0681 , B01L2300/0816 , B01L2300/0887 , B01L2300/10 , B01L2400/0633 , B01L2400/086 , C12M23/16 , C12M25/14 , C12M29/04 , C12M29/10 , C12M35/08 , C12M41/46
摘要： A bioreactor with substance injection capability. In one embodiment, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a chamber for receiving cells and a liquid medium. A port is formed in the second substrate between the bottom surface and the first surface of the second substrate. As formed, the port is in fluid communication with the chamber to allow a stream of substance to be introduced into the chamber. The stream of substance is controlled so as to provide a gradient, or a concentration gradient of the substance, to the chamber. The stream of substance includes a substance affecting the growth of cells such as chemokine.
摘要翻译：具有物质注入能力的生物反应器。在一个实施例中，生物反应器包括具有第一表面，相对的第二表面和边缘的第一基底。生物反应器还包括具有第一表面和相对的第二表面的第二基底，其限定具有底表面的空腔，其中底表面位于第一表面和第二表面之间。第一基板的第一表面被第二基板的第二表面接收以覆盖空腔，以形成用于容纳电池和液体介质的室。在第二基板的第二基板的底表面和第一表面之间形成端口。如此形成的，端口与腔室流体连通，以允许物质流被引入腔室。物质流被控制以便向腔室提供物质的梯度或浓度梯度。物质流包括影响细胞生长的物质，如趋化因子。

29. 发明授权

US07763017B2 Selective photocoagulation apparatus 有权
标题翻译：选择性凝固装置
公开(公告)号：US07763017B2
公开(公告)日：2010-07-27
申请号：US11428018
申请日：2006-07-26
申请人： Charles P. Lin
发明人： Charles P. Lin
IPC分类号： A61B18/20
CPC分类号： A61B18/20 , A61B2017/00057 , A61B2018/00636 , A61B2018/00642 , A61F9/008 , A61F9/00821 , A61F2009/00844 , A61F2009/00855 , A61F2009/00863 , A61F2009/00897
摘要： A method of scanning a laser beam across a set of cells includes during a first interval, scanning a laser beam across a set of cells; and during a second interval, deflecting the laser beam away from the set of cells. The first interval is selected to cause microcavitation in at least a portion of the cells from the set of cells.
摘要翻译：扫描激光束跨越一组单元的方法包括在第一间隔期间扫描激光束穿过一组单元; 并且在第二间隔期间，使激光束偏离该组电池。选择第一间隔以在来自该组细胞的至少一部分细胞中引起微腔化。

30. 发明申请

US20090215654A1 Capillary Perfused Bioreactors with Multiple Chambers 有权
标题翻译：具有多个腔室的毛细管灌注生物反应器
公开(公告)号：US20090215654A1
公开(公告)日：2009-08-27
申请号：US12398825
申请日：2009-03-05
申请人： John P. Wikswo , Franz J. Baudenbacher , Ales Prokop , Eugene J. Leboeuf , Chang Y. Chung , David Cliffel , Frederick R. Haselton , William H. Hofmeister , Charles P. Lin , Lisa J. McCawley , Randall S. Reiserer , Mark A. Stremler
发明人： John P. Wikswo , Franz J. Baudenbacher , Ales Prokop , Eugene J. Leboeuf , Chang Y. Chung , David Cliffel , Frederick R. Haselton , William H. Hofmeister , Charles P. Lin , Lisa J. McCawley , Randall S. Reiserer , Mark A. Stremler
IPC分类号： C40B60/00 , C12M1/00 , G01N27/26 , G01N33/50
CPC分类号： B01L3/502761 , B01L3/502746 , B01L2200/0668 , B01L2300/0816 , B01L2300/0864 , B01L2300/0877 , B01L2300/10 , B01L2400/0406 , B01L2400/0415 , B01L2400/0487 , C12M23/16 , C12M29/10
摘要： A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving cells and a liquid medium. In forming the bioreactor, the channel is sized to allow the growth of a layer of cells on a biocompatible coating layer and a flow of liquid in the channel. The flow of liquid is controlled so as to provide a known shear force to the layer of cells. The flow of liquid can be further controlled so as to provide an environment that simulates a vascular space in the channel.
摘要翻译：用于在液体培养基中培养活细胞的生物反应器。在本发明的一个实施方案中，生物反应器包括具有第一表面，相对的第二表面和边缘的第一基底。生物反应器还包括具有第一表面和相对的第二表面的第二基底，其限定具有底表面的空腔，其中底表面位于第一表面和第二表面之间。第一基板的第一表面由第二基板的第二表面接收以覆盖空腔，以形成用于接收电池和液体介质的通道。在形成生物反应器时，通道的大小适于允许生物相容性涂层上的细胞层的生长和通道中的液体流。控制液体的流动以便向细胞层提供已知的剪切力。可以进一步控制液体的流动，以便提供模拟通道中血管空间的环境。

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