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1. 发明申请

US20100120113A1 APPARATUS AND METHOD FOR MICROMANIPULATION OF MICROSCALE OBJECTS USING LASER LIGHT DELIVERED THROUGH A SINGLE OPTICAL FIBER AND AXICON LENS 有权
标题翻译：使用通过单个光纤和AXICON镜头提供的激光照射微观物体的装置和方法
公开(公告)号：US20100120113A1
公开(公告)日：2010-05-13
申请号：US12613472
申请日：2009-11-05
申请人： Samarendra K. Mohanty , Jared Stephens , Suzanne Genc , Michael W. Berns
发明人： Samarendra K. Mohanty , Jared Stephens , Suzanne Genc , Michael W. Berns
IPC分类号： C12N13/00 , G02B6/32 , H01S3/091
CPC分类号： C12N13/00 , C12M35/02 , G02B6/262 , G02B21/32
摘要： A single optical fiber having a distal end is optically coupled to the laser and distilling terminated with an axicon lens optically coupled to the single optical fiber to form a microscopic distal tip to provide a spatially shaped elongated laser focused spot for microprocessing and/or microdissection of a microscale object. A pulsed or continuous laser beam or superposition of pulsed and continuous laser beams is generated, controllably spatially shaped, selectively oriented, selectively moved via movement of a single optical fiber terminated with the axicon lens, and the oriented, spatially shaped laser beam applied via the single optical fiber terminated with the axicon lens to a living or nonliving microscopic object for manipulation, micro-dissection, alteration/ablation, and excitation of the living or nonliving microscopic object.
摘要翻译：具有远端的单个光纤光学耦合到激光器并蒸馏，其终端具有光学耦合到单个光纤的旋转透镜，以形成微观远端，以提供用于微处理和/或显微切割的空间形状的细长激光聚焦点一个微型对象。产生脉冲或连续的激光束或脉冲和连续激光束的叠加，可控地空间形状，选择性地定向，通过由透镜透镜终止的单个光纤的移动选择性地移动，并且经由用光学透镜终止的单个光纤到活的或非活性的微观物体用于操作，微观解剖，改变/消融和激活生物或非活性微观物体。

2. 发明授权

US5631141A High resolution biosensor for in-situ microthermometry 失效
标题翻译：高分辨率生物传感器用于原位微量测定
公开(公告)号：US5631141A
公开(公告)日：1997-05-20
申请号：US435354
申请日：1995-05-05
申请人： Gregory J. Sonek , Yagang Liu , Bruce J. Tromberg , Michael W. Berns
发明人： Gregory J. Sonek , Yagang Liu , Bruce J. Tromberg , Michael W. Berns
IPC分类号： G01N31/22 , C12Q1/02
CPC分类号： G01N31/229 , Y10S435/968
摘要： The present invention comprises a method for use of a biosensor for in-situ microthermometry. This biosensor is a substantially spherical vesicle impregnated with a dopant which varies its optical emission spectrum as a function of the local environmental temperature of the biosensor in the temperature range to be observed. In the preferred embodiment of the present invention, this dopant is the fluorescent dye 6-dodecanoyl-2-dimethylamino-naphthalene (Laurdan.TM.). This method for in-situ measurement of temperature in a biological system uses such a vesicle by introduction of the vesicle into the biological system to be measured and manipulation of the vesicle to the location where temperature is to be measured. The temperature is then calculated from the optically measured generalized polarization at that location and the known relationship between temperature and generalized polarization for the membrane of the vesicle.
摘要翻译：本发明包括使用生物传感器进行原位微量测定的方法。该生物传感器是浸渍有掺杂剂的基本上球形的囊泡，其在要观察的温度范围内改变其作为生物传感器的局部环境温度的函数的光发射光谱。在本发明的优选实施方案中，该掺杂剂是荧光染料6-十二酰基-2-二甲基氨基 - 萘（Laurdan TM）。用于生物系统中温度原位测量的方法通过将囊泡引入要测量的生物系统中并将囊泡操作到要测量温度的位置来使用这种囊泡。然后从该位置处的光学测量的广义极化计算温度，以及温度和囊泡膜的广义极化之间的已知关系。

3. 发明授权

US09321990B2 Systems and methods for identifying and disrupting cellular organelles 有权
标题翻译：识别和破坏细胞器的系统和方法
公开(公告)号：US09321990B2
公开(公告)日：2016-04-26
申请号：US13234986
申请日：2011-09-16
申请人： Michael W. Berns , Thoru Pederson , Elliot Botvinick , Linda Zhixia Shi
发明人： Michael W. Berns , Thoru Pederson , Elliot Botvinick , Linda Zhixia Shi
IPC分类号： C12Q1/00 , H01S3/00 , G01N35/08 , C12M1/42 , C12M1/00 , G01N15/14
CPC分类号： C12M35/02 , C12M47/06 , G01N15/1475 , G01N2015/149 , Y10T436/12
摘要： This invention relates to optomechanical systems and methods for altering, modifying or disrupting a target object. Such systems and methods are used for, for example, ablating the endogenous nucleus in a cell.
摘要翻译：本发明涉及用于改变，修改或破坏目标物体的光学机械系统和方法。这样的系统和方法用于例如消除细胞内的内源核。

4. 发明授权

US06661574B2 Diffuse optics illuminator for reflectance microscopy and method of providing diffuse light for reflectance microscopy 失效
标题翻译：用于反射显微镜的漫射光学照明器和用于反射显微镜的漫射光的方法
公开(公告)号：US06661574B2
公开(公告)日：2003-12-09
申请号：US10126141
申请日：2002-04-19
申请人： Tatiana B. Krasieva , Alexander S. Dvornikov , Bruce J. Tromberg , Michael W. Berns
发明人： Tatiana B. Krasieva , Alexander S. Dvornikov , Bruce J. Tromberg , Michael W. Berns
IPC分类号： G02B2106
CPC分类号： G02B21/125
摘要： An illuminator and a reflectance microscope or system utilizing the illuminator for eliminating the need of a special light source, a reflected light vertical illuminator, and condenser lenses. The system may utilize an ordinary light source. The illuminator includes embedded chromophoric and diffusion properties. The illuminator further has a size and a shape to enable proximate positioning relative to the specimen to be observed. The illuminator further has an opening or aperture through which the specimen may be viewed. As such, the opening of the illuminator permits placement of the illuminator between the objective lens and the specimen. This positioning enables reflectance type or dark field microscopy with a simple and durable illuminator without complex optics. A method of using the reflectance microscope includes illuminating a specimen by the illuminator on a same side of the specimen as is the objective lens relative to a plane of the specimen normal to the optical path.
摘要翻译：使用照明器的照明器和反射显微镜或系统，用于消除对特殊光源，反射光垂直照明器和聚光透镜的需要。该系统可以利用普通的光源。照明器包括嵌入式发色和扩散特性。照明器还具有尺寸和形状，以使得能够相对于要观察的样本的邻近定位。照明器还具有可以观察样本的开口或孔。因此，照明器的开口允许照明器在物镜和样本之间放置。这种定位使得反射型或暗视野显微镜具有简单耐用的照明器，无需复杂的光学元件。使用反射型显微镜的方法包括：在与所述物镜相同的样本的与所述光路的垂直方向的平面相同的侧面照射所述样本。

5. 发明申请

US20100209963A1 PHOTO-ELECTRIC DEVICE AND METHOD FOR HIGH THROUGHPUT ACTIVATION, GUIDANCE AND PORATION OF TARGETED CELLS WITH HIGH SPATIAL RESOLUTION 审中-公开
标题翻译：具有高空间分辨率的高通量激活，指导和靶向细胞的光电装置和方法
公开(公告)号：US20100209963A1
公开(公告)日：2010-08-19
申请号：US12705517
申请日：2010-02-12
申请人： Khyati P. Dave , Samarenda K. Mohanty , Michael W. Berns
发明人： Khyati P. Dave , Samarenda K. Mohanty , Michael W. Berns
IPC分类号： C12Q1/02 , C12N13/00 , C12N15/00 , C12M1/00 , C12N5/07
CPC分类号： C12M35/02 , C12Q1/025 , G01N33/5044 , G01N33/5058 , G01N33/5061
摘要： The method includes the steps of generating a spatially and/or temporally localized electric field generated on the photoconductive surface, and selectively activating, guiding or porating targeted (excitable) cells at high throughput with high spatial resolution, applied for example to neurons, cardiac and muscle cells. The spatially and/or temporally localized electric field can be established using spatially and/or temporally patterning light with a diffractive element to generate the spatially localized electric field on the photoconductive surface which is sandwiched between two conductive surfaces and applying a selected voltage difference between the two conductive surfaces. The intensity of the light beam can be varied for different processes of activation, guidance or poration without causing cellular damage.
摘要翻译：该方法包括以下步骤：产生在光电导表面上产生的空间和/或时间上定位的电场，并且以高生产率以高空间分辨率选择性地激活，引导或打孔目标（可兴奋的）细胞，例如应用于神经元，心脏和肌肉细胞。空间和/或时间局部化电场可以使用空间和/或时间图案化具有衍射元件的光来建立，以在光电导表面上产生空间局部电场，该电场夹在两个导电表面之间，并且在两个导电表面。对于不同的激活，引导或定位过程，光束的强度可以变化，而不会造成细胞损伤。

6. 发明授权

US07157223B2 Method and apparatus for detecting enzymatic activity using molecules that change electrophoretic mobility 失效
标题翻译：使用改变电泳迁移率的分子检测酶活性的方法和装置
公开(公告)号：US07157223B2
公开(公告)日：2007-01-02
申请号：US09945396
申请日：2001-08-30
申请人： Nancy Allbritton , Christopher Sims , Michael W. Berns , Gavin D. Meredith , Tatiana B. Krasieva , Bruce J. Tromberg , Chao L. Lee
发明人： Nancy Allbritton , Christopher Sims , Michael W. Berns , Gavin D. Meredith , Tatiana B. Krasieva , Bruce J. Tromberg , Chao L. Lee
IPC分类号： C12Q1/00
CPC分类号： C12M41/46 , C12M35/02 , C12M47/06 , C12Q1/00 , C12Q1/485 , G01N27/44721 , G01N27/44743 , G01N33/50 , G01N33/5017
摘要： The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and enzymatic activity is determined by comparing amounts of substrate molecules to amounts of enzymatically altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.
摘要翻译：通过使用荧光标记的底物分子来测量分子的细胞内化学反应的活性，所述底物分子在诸如由酶催化的化学反应时经历电泳迁移率的变化。通过使用只能被特定酶作用的标记底物分子来实现特异性。因此，可以确定特异性酶或酶类的活性。通常在感兴趣的某个时间通常在将细胞暴露于激活特定酶促途径的刺激之后，通过细胞内存在这样的底物分子进行测量。为了确保准确性，必须及时进行测量，以最大限度地减少感兴趣的时间后发生的化学反应。使用快速可控的激光裂解来获得引入了报告基质分子的单细胞的含量。然后对细胞内容物进行毛细管电泳，并通过将底物分子的量与通过电泳分离并通过荧光标记的存在鉴定的酶促改变的底物分子的量进行比较来确定酶活性。

7. 发明授权

US06322556B1 Method of laser photoablation of lenticular tissue for the correction of vision problems 失效
标题翻译：用于矫正视力问题的透镜组织的激光光切割方法
公开(公告)号：US06322556B1
公开(公告)日：2001-11-27
申请号：US08103089
申请日：1993-08-06
申请人： Arlene E. Gwon , Michael W. Berns
发明人： Arlene E. Gwon , Michael W. Berns
IPC分类号： A61F9008
CPC分类号： A61F9/008 , A61F9/00736 , A61F9/00802 , A61F2009/00853 , A61F2009/0087 , A61F2009/00887 , A61F2009/00895
摘要： A method for the laser photoablation of ocular lens tissue comprises the steps of determining a volume of the lens tissue to be photoablated and directing a pulsed, infrared laser beam at the volume with an amount of energy effective for photoablating the determined region without causing substantial damage to surrounding tissue regions. The laser beam is initially directed at a focal point below an anterior surface of the ocular lens and such focal point is moved towards the ocular lens anterior surface in order to ablate the determined volume. The laser is preferably an Nd:YLF laser operating at a frequency of about 1053 nanometers and a pulse repetition rate of about 1000 Hertz with a pulse width of about 60 picoseconds. Each pulse has an energy of about 30 microjoules. The laser operates with a focused beam diameter of about 20 microns and operates with a “zone of effect” of no greater than about 50 microns. The method provides for the correction of myopia, hyperopia or presbyopia and enables the removal of incipient cataract.
摘要翻译：用于眼透镜组织的激光光切割的方法包括以下步骤：确定要光照的透镜组织的体积，并以一定量的能量对脉冲的红外激光束进行照射，以有效地对确定的区域进行照相，而不会造成实质的损伤到周围的组织区域。激光束最初被引导到眼透镜的前表面下方的焦点处，并且这样的焦点朝向眼透镜前表面移动以便消融确定的体积。该激光器优选为以约1053纳米的频率工作的Nd：YLF激光器，脉冲重复率约为1000赫兹，脉冲宽度约为60皮秒。每个脉冲具有约30微焦耳的能量。激光器以约20微米的聚焦光束直径进行操作，并以不大于约50微米的“效应区域”操作。该方法提供矫正近视，远视或老花眼，并能够去除早期白内障。

8. 发明授权

US5478339A Intrauterine device for laser light diffusion and method of using the same 失效
标题翻译：用于激光扩散的子宫内装置及其使用方法
公开(公告)号：US5478339A
公开(公告)日：1995-12-26
申请号：US297752
申请日：1994-08-30
申请人： Yona Tadir , Michael W. Berns , Lars O. Svaasand , Bruce J. Tromberg
发明人： Yona Tadir , Michael W. Berns , Lars O. Svaasand , Bruce J. Tromberg
IPC分类号： A61B18/20 , A61B18/22 , A61N5/06 , A61B17/36
CPC分类号： A61N5/062 , A61N5/0601 , A61B2018/2261 , A61N2005/0611
摘要： An improved device for delivery of photoenergy from a light source, such as a laser, into a uterine cavity for photodynamic therapy is comprised of a plurality of optic fibers, which are bundled together and inserted into the uterine cavity by means of a uterine cannula. The cannula is positioned within the uterine cavity at a preferred location and then withdrawn thereby allowing the plurality of optic fibers to splay or diverge one from the other within the cavity. Different portions of the distal tip of the optic fiber is provided with a light diffusing tip, the remainder being provided with a nondiffusing tip portion. The fiber optic shape, as well as the segment which is permitted to actively diffuse light through the tip, is selected in order to provide a more uniform exposure intensity of the photo energy or at least sufficient radiation directed to each segment of the uterine walls.
摘要翻译：用于将光能从诸如激光器的光源递送到用于光动力疗法的子宫腔中的改进的装置由多个光纤组成，多个光纤通过子宫套管捆绑在一起并插入到子宫腔中。套管位于子宫腔内的优选位置处，然后被抽出，从而允许多个光纤在空腔内使另一个光纤展开或发散。光纤的远端的不同部分设置有光扩散尖端，其余部分设置有非扩散尖端部分。选择纤维光学形状以及被允许主动地通过尖端漫射光束的片段，以便提供光能的更均匀的曝光强度或至少足够的辐射指向子宫壁的每个部分。

9. 发明授权

US5458595A Vaginal speculum for photodynamic therapy and method of using the same 失效
标题翻译：阴道窥器用于光动力疗法及其使用方法
公开(公告)号：US5458595A
公开(公告)日：1995-10-17
申请号：US168553
申请日：1993-12-16
申请人： Yona Tadir , Michael W. Berns , Brad J. Monk , Glen Profeta , Bruce J. Tromberg
发明人： Yona Tadir , Michael W. Berns , Brad J. Monk , Glen Profeta , Bruce J. Tromberg
IPC分类号： A61B1/32 , A61B17/22 , A61B17/42 , A61B18/22 , A61B19/00 , A61N5/06 , A61B17/32
CPC分类号： A61B1/32 , A61B1/07 , A61B17/42 , A61B18/22 , A61N5/0601 , A61N5/062 , A61B2017/22087 , A61B2090/062
摘要： An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.
摘要翻译：用于上皮内组织，特别是阴道，宫颈和外阴肿瘤的光动力治疗的改进的阴道窥器利用精确和准确的可定位的光纤，通过该光纤将620-700纳米范围内的预定剂量的光量传送到具有以前用光动力治疗物质治疗。特别地，肿瘤区域已被血卟啉衍生物和其它选择性摄入癌组织的光敏剂中治疗。暴露于合适的波长激光光激活吸收的血卟啉，导致释放内在氧化并最终导致细胞死亡的单线态氧。将激光从其传播的光纤尖端精确地定位在距离上皮内瘤变形预定距离的体腔内，以便获得适当的斑点大小和位置，以最小化对健康组织的损伤并最大限度地损害选择性浸润的癌性组织。

10. 发明授权

US09089698B2 Method and apparatus for optogenetic treatment of blindness including retinitis pigmentosa 有权
标题翻译：视网膜色素变性眼病的治疗方法及装置
公开(公告)号：US09089698B2
公开(公告)日：2015-07-28
申请号：US12760520
申请日：2010-04-14
申请人： Samarenda K. Mohanty , Matthew Ficinski , Edward K. Wong , Michael W. Berns
发明人： Samarenda K. Mohanty , Matthew Ficinski , Edward K. Wong , Michael W. Berns
IPC分类号： A61N1/32 , A61N1/04 , A61F9/00 , A61K9/00 , A61K38/17
CPC分类号： A61N1/327 , A61F9/0017 , A61K9/0048 , A61K38/177 , A61N1/0412 , A61N1/0416
摘要： An apparatus for in vivo electroporating a plasmid into a retina of any eye includes a first electrode with a first polarity of voltage placed in contact with a cornea of the eye, a second electrode with an opposite second voltage at least in part behind the retina, and a pulsed voltage source for providing a pulsed DC voltage with an optimized field strength amplitude, frequency, number of pulses, group repetition rate and duration of pulse and group repetition, which are optimized for transfection of the channelrhodospsin-2 (ChR2) gene into the retinal ganglion cells. An in vivo method for treating retinal ganglion cells in an eye without use of viral transfection includes the steps of nonviral in vivo delivering a channelrhodospsin-2 (ChR2) gene to target the specific (retinal ganglion) cells of a retina by intravitreous injection of plasmid DNA, electroporating the plasmid into the retina and use of image intensification device for stimulating the retinal ganglion cells with ambient lighting conditions.
摘要翻译：用于体内将质粒电穿孔到任何眼睛的视网膜的装置包括具有第一极性电压的第一电极与眼睛的角膜接触，第二电极具有至少部分地在视网膜后方的相反的第二电压，以及脉冲电压源，用于提供具有优化的场强振幅，频率，脉冲数，组重复率和脉冲和组重复持续时间的脉冲DC电压，其被优化用于将渠道样细胞蛋白酶-2（ChR2）基因转染到视网膜神经节细胞。用于在眼睛内治疗视网膜神经节细胞而不使用病毒转染的体内方法包括以下步骤：通过玻璃体内注射质粒，非病毒体内递送通道寡聚胰蛋白胨-2（ChR2）基因靶向视网膜的特定（视网膜神经节）细胞 DNA，将质粒电穿孔到视网膜中，并使用图像增强装置用环境照明条件刺激视网膜神经节细胞。

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