公开(公告)号：US08575570B2

公开(公告)日：2013-11-05

申请号：US13217580

申请日：2011-08-25

申请人： John M. Choi ,  Thai V. Truong ,  David S. Koos

发明人： John M. Choi ,  Thai V. Truong ,  David S. Koos

IPC分类号： F21V9/16

CPC分类号： G01N21/4795 ,  G01N21/6458 ,  G02B21/367

摘要： An apparatus for and method of performing orthogonal light sheet microscopy (OLM) and computer optical tomography (COT) simultaneously in a single device are provided. The dual-mode imaging microscope allows for the use of both OLM and COT in a single instrument. This dual-mode device will allow researchers to have access to both types of microscopy, allowing access to the widest possible selection of samples, and improved imaging results. In addition, the device will reduce the high costs and space requirements associated with owning two different imagers (OLM and COT).

摘要翻译： 提供了在单个设备中同时执行正交光谱显微镜（OLM）和计算机光学层析成像（COT）的装置和方法。 双模显微镜允许在单个仪器中使用OLM和COT。 这种双模式设备将允许研究人员访问这两种类型的显微镜，允许访问尽可能多的样品选择和改进的成像结果。 此外，该设备将降低与拥有两个不同成像器（OLM和COT）相关的高成本和空间要求。

公开(公告)号：US20110122488A1

公开(公告)日：2011-05-26

申请号：US12915921

申请日：2010-10-29

申请人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

发明人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

IPC分类号： G02B21/06

CPC分类号： G02B21/16 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/6486 ,  G01N2021/655 ,  G02B21/002 ,  G02B21/367

摘要： An apparatus for and method of performing multi-photon light sheet microscopy (MP-LISH), combining multi-photon excited fluorescence with the orthogonal. illumination of light sheet microscopy are provided. With live imaging of whole Drosophila and zebrafish embryos, the high performance of MP-LISH compared to current state-of-the-art imaging techniques in maintaining good signal and high spatial resolution deep inside biological tissues (two times deeper than one-photon light sheet microscopy), in acquisition speed (more than one order of magnitude faster than conventional two-photon laser scanning microscopy), and in low phototoxicity are demonstrated. The inherent multi-modality of this new imaging technique is also demonstrated second harmonic generation light sheet microscopy to detect collagen in mouse tail tissue. Together, these properties create the potential for a wide range of applications for MP-LISH in 4D imaging of live biological systems.

摘要翻译： 一种多光子激光荧光与正交结合的多光子光谱显微镜（MP-LISH）的设备和方法。 提供了光片显微镜的照明。 通过对整个果蝇和斑马鱼胚胎的实时成像，MP-LISH的高性能与目前最先进的成像技术相比，保持生物组织内部的良好信号和高空间分辨率（比单光子光更深两倍） 片状显微镜），在采集速度（比常规双光子激光扫描显微镜快超过一个数量级），并且具有低的光毒性。 这种新的成像技术的固有多模态也被证明了二次谐波发生光谱显微镜检测小鼠尾部组织中的胶原蛋白。 共同的，这些属性为MP-LISH在活体生物系统4D成像中的应用提供了广泛的应用。

公开(公告)号：US08441633B2

公开(公告)日：2013-05-14

申请号：US12915921

申请日：2010-10-29

申请人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

发明人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

IPC分类号： G01J3/40 ,  G01J3/30 ,  G01J1/58 ,  F21V9/16 ,  G01T1/10 ,  G21H3/02 ,  G21K5/00 ,  H01J65/06 ,  H01J65/08

CPC分类号： G02B21/16 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/6486 ,  G01N2021/655 ,  G02B21/002 ,  G02B21/367

摘要： An apparatus for and method of performing multi-photon light sheet microscopy (MP-LISH), combining multi-photon excited fluorescence with the orthogonal illumination of light sheet microscopy are provided. With live imaging of whole Drosophila and zebrafish embryos, the high performance of MP-LISH compared to current state-of-the-art imaging techniques in maintaining good signal and high spatial resolution deep inside biological tissues (two times deeper than one-photon light sheet microscopy), in acquisition speed (more than one order of magnitude faster than conventional two-photon laser scanning microscopy), and in low phototoxicity are demonstrated. The inherent multi-modality of this new imaging technique is also demonstrated second harmonic generation light sheet microscopy to detect collagen in mouse tail tissue. Together, these properties create the potential for a wide range of applications for MP-LISH in 4D imaging of live biological systems.

摘要翻译： 提供了一种多光子激光荧光与光谱显微镜正交照明相结合的多光子光谱显微镜（MP-LISH）的设备和方法。 通过对整个果蝇和斑马鱼胚胎的实时成像，MP-LISH的高性能与目前最先进的成像技术相比，保持生物组织内部的良好信号和高空间分辨率（比单光子光更深两倍） 片状显微镜），在采集速度（比常规双光子激光扫描显微镜快超过一个数量级），并且具有低的光毒性。 这种新的成像技术的固有多模态也被证明了二次谐波发生光片显微镜检测小鼠尾部组织中的胶原蛋白。 共同的，这些属性为MP-LISH在活体生物系统4D成像中的应用提供了广泛的应用。

公开(公告)号：US20090041316A1

公开(公告)日：2009-02-12

申请号：US12188076

申请日：2008-08-07

申请人： David S. Koos ,  Scott E. Fraser

发明人： David S. Koos ,  Scott E. Fraser

IPC分类号： G06K9/00

CPC分类号： G06K9/4638 ,  G02B21/367 ,  G06K9/00134

摘要： An system and method provide the ability to image a biological sample. A sample is embed to a support matrix that is compatible with an aqueous nature of the sample. A vibrating tissue sectioning system is coupled to a microscope and is used to remove a region of the sample without moving the sample. The sectioning of the sample occurs under a surface of an aqueous buffer in a basin. A positioning system enables the microscope to image adjacent sub-regions of the sample. The microscope image multiple sections of the sample in adjacent subregions using the vibrating tissue sectioning system and the positioning system.

摘要翻译： 系统和方法提供了对生物样品进行成像的能力。 将样品嵌入到与样品的水性质相容的载体基质中。 振动的组织切片系统耦合到显微镜并且用于去除样品的区域而不移动样品。 样品的切片发生在盆中的水性缓冲液的表面下。 定位系统使显微镜能够对样品的相邻子区域进行成像。 显微镜图像使用振动组织切片系统和定位系统在相邻次区域中的样品的多个部分。

公开(公告)号：US20120049087A1

公开(公告)日：2012-03-01

申请号：US13217580

申请日：2011-08-25

申请人： John M. Choi ,  Thai V. Truong ,  David S. Koos

发明人： John M. Choi ,  Thai V. Truong ,  David S. Koos

IPC分类号： G01J1/58 ,  G01J3/44 ,  G01N21/59 ,  G02B21/36

CPC分类号： G01N21/4795 ,  G01N21/6458 ,  G02B21/367

摘要： An apparatus for and method of performing orthogonal light sheet microscopy (OLM) and computer optical tomography (COT) simultaneously in a single device are provided. The dual-mode imaging microscope allows for the use of both OLM and COT in a single instrument. This dual-mode device will allow researchers to have access to both types of microscopy, allowing access to the widest possible selection of samples, and improved imaging results. In addition, the device will reduce the high costs and space requirements associated with owning two different imagers (OLM and COT).

摘要翻译： 提供了在单个设备中同时执行正交光谱显微镜（OLM）和计算机光学层析成像（COT）的装置和方法。 双模显微镜允许在单个仪器中使用OLM和COT。 这种双模式设备将允许研究人员访问这两种类型的显微镜，允许访问尽可能多的样品选择和改进的成像结果。 此外，该设备将降低与拥有两个不同成像器（OLM和COT）相关的高成本和空间要求。

公开(公告)号：US20100000383A1

公开(公告)日：2010-01-07

申请号：US12583471

申请日：2009-08-21

申请人： David S. Koos ,  John M. Choi

发明人： David S. Koos ,  John M. Choi

IPC分类号： B26D7/08 ,  B26D7/06 ,  G06K9/00

CPC分类号： G01N1/06 ,  G01N1/36 ,  G02B21/32 ,  G02B21/367 ,  G06K9/00134 ,  G06K9/4638 ,  Y10T83/0443 ,  Y10T83/202 ,  Y10T83/242

摘要： The present invention relates to a microscope coupled tissue sectioning system. The tissue sectioning system includes a frame for coupling with a microscope. A sample cutting apparatus is attached with the frame. The sample cutting apparatus includes a sample cutter (e.g., blade) and is operable for causing the sample cutter to engage with the sample and remove a portion of the sample. Additionally, a sample moving apparatus attached with the frame. The sample moving apparatus is operable for causing the sample to align with an imaging path of a microscope for imaging by the microscope.

摘要翻译： 本发明涉及一种显微镜联合组织切片系统。 组织切片系统包括用于与显微镜联接的框架。 样品切割装置与框架相连。 样品切割装置包括样品切割器（例如刀片），并且可操作以使样品切割器与样品接合并除去样品的一部分。 另外，安装有框架的样品移动装置。 样品移动装置可操作用于使样品与显微镜的成像路径对准以通过显微镜成像。

公开(公告)号：US08570649B2

公开(公告)日：2013-10-29

申请号：US12916124

申请日：2010-10-29

申请人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

发明人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

IPC分类号： G02B21/06 ,  G02B21/00

CPC分类号： G02B21/16 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/6486 ,  G01N2021/655 ,  G02B21/002 ,  G02B21/367

摘要： An apparatus for and method of performing light sheet microscopy (LISH) and light scanning microscopy (RAPS) in a single device are provided. The dual-mode imaging microscope allows for the use of both LISH and RAPS in a single instrument. This dual-mode device will allow researchers to have access to both types of microscopy, allowing access to the widest possible selection of samples. In addition, the device will reduce the high costs and space requirements associated with owning two different microscopes (LISH and RAPS).

摘要翻译： 提供了在单个装置中执行光谱显微镜（LISH）和光扫描显微镜（RAPS）的装置和方法。 双模式成像显微镜允许在单个仪器中使用LISH和RAPS。 这种双模式设备将使研究人员能够访问这两种类型的显微镜，从而允许访问尽可能多的样品。 此外，该设备将降低与拥有两台不同显微镜（LISH和RAPS）相关的高成本和空间要求。

公开(公告)号：US20110134521A1

公开(公告)日：2011-06-09

申请号：US12916124

申请日：2010-10-29

申请人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

发明人： Thai V. Truong ,  John M. Choi ,  Scott E. Fraser ,  Willy Supatto ,  David S. Koos

IPC分类号： G02B21/06

CPC分类号： G02B21/16 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6458 ,  G01N21/6486 ,  G01N2021/655 ,  G02B21/002 ,  G02B21/367

摘要： An apparatus for and method of performing light sheet microscopy (LISH) and light scanning microscopy (RAPS) in a single device are provided. The dual-mode imaging microscope allows for the use of both LISH and RAPS in a single instrument. This dual-mode device will allow researchers to have access to both types of microscopy, allowing access to the widest possible selection of samples. In addition, the device will reduce the high costs and space requirements associated with owning two different microscopes (LISH and RAPS).

摘要翻译： 提供了在单个装置中执行光谱显微镜（LISH）和光扫描显微镜（RAPS）的装置和方法。 双模式成像显微镜允许在单个仪器中使用LISH和RAPS。 这种双模式设备将使研究人员能够访问这两种类型的显微镜，从而允许访问尽可能多的样品。 此外，该设备将减少与拥有两台不同显微镜（LISH和RAPS）相关的高成本和空间要求。

公开(公告)号：US20090110638A1

公开(公告)日：2009-04-30

申请号：US12257616

申请日：2008-10-24

申请人： David S. KOOS

发明人： David S. KOOS

IPC分类号： A61K38/00 ,  A61K49/00 ,  C12Q1/48 ,  C12Q1/44 ,  C12Q1/02

CPC分类号： G01N33/566 ,  A61K31/00 ,  G01N33/5058 ,  G01N2500/00

摘要： The present invention relates to physical and pharmaceutical methods of increasing or decreasing the activity of the Grueneberg Ganglion (GG) in a subject. In one embodiment, the method comprising administering a compound to the GG, wherein the compound is an agonist or antagonist, respectively, for at least one guanylyl cyclase receptor or the receptor's downstream effectors. The present invention also relates to methods of screening candidate compounds for their ability to modulate the activity of the GG. The present invention also relates to methods and kits for positively identifying a GG neuron based upon the presence or absence of the pGC-G or pGC-A receptors.

摘要翻译： 本发明涉及在受试者中增加或减少Grueneberg神经节（GG）的活性的物理和药物方法。 在一个实施方案中，所述方法包括向GG施用化合物，其中所述化合物分别是至少一种鸟苷酸环化酶受体或受体的下游效应物的激动剂或拮抗剂。 本发明还涉及筛选候选化合物以调节GG活性的能力的方法。 本发明还涉及用于基于pGC-G或pGC-A受体的存在或不存在来正确鉴定GG神经元的方法和试剂盒。