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1. 发明授权

US08772693B2 System and method for Hilbert phase imaging 有权
标题翻译：希尔伯特相位成像系统和方法
公开(公告)号：US08772693B2
公开(公告)日：2014-07-08
申请号：US11389670
申请日：2006-03-24
申请人： Gabriel Popescu , Ramachandra Dasari , Takahiro Ikeda
发明人： Gabriel Popescu , Ramachandra Dasari , Michael Feld , Takahiro Ikeda
IPC分类号： H01L27/00
CPC分类号： H01L27/14601 , G01N15/10 , G01N15/1475 , G01N21/453 , G01N33/49 , G01N2015/0073 , G01N2015/008 , G01N2015/145 , G01N2015/1454 , G01N2015/1497 , G06K9/00134
摘要： Hilbert phase microscopy (HPM) as an optical technique for measuring high transverse resolution quantitative phase images associated with optically transparent objects. Due to its single-shot nature, HPM is suitable for investigating rapid phenomena that take place in transparent structures such as biological cells. A preferred embodiment is used for measuring biological systems including measurements on red blood cells, while its ability to quantify dynamic processes on the millisecond scale, for example, can be illustrated with measurements on evaporating micron-size water droplets.
摘要翻译：希尔伯特相位显微镜（HPM）作为用于测量与光学透明物体相关的高横向分辨率定量相位图像的光学技术。由于其单次性质，HPM适用于调查在诸如生物细胞的透明结构中发生的快速现象。优选的实施例用于测量生物系统，包括对红血细胞的测量，而其量化毫秒级别的动态过程的能力可以用蒸发微米级水滴的测量来说明。

2. 发明申请

US20060291712A1 System and method for Hilbert phase imaging 有权
标题翻译：希尔伯特相位成像系统和方法
公开(公告)号：US20060291712A1
公开(公告)日：2006-12-28
申请号：US11389670
申请日：2006-03-24
申请人： Gabriel Popescu , Ramachandra Dasari , Michael Feld , Takahiro Ikeda
发明人： Gabriel Popescu , Ramachandra Dasari , Michael Feld , Takahiro Ikeda
IPC分类号： G06K9/00
CPC分类号： H01L27/14601 , G01N15/10 , G01N15/1475 , G01N21/453 , G01N33/49 , G01N2015/0073 , G01N2015/008 , G01N2015/145 , G01N2015/1454 , G01N2015/1497 , G06K9/00134
摘要： Hilbert phase microscopy (HPM) as an optical technique for measuring high transverse resolution quantitative phase images associated with optically transparent objects. Due to its single-shot nature, HPM is suitable for investigating rapid phenomena that take place in transparent structures such as biological cells. A preferred embodiment is used for measuring biological systems including measurements on red blood cells, while its ability to quantify dynamic processes on the millisecond scale, for example, can be illustrated with measurements on evaporating micron-size water droplets.
摘要翻译：希尔伯特相位显微镜（HPM）作为用于测量与光学透明物体相关的高横向分辨率定量相位图像的光学技术。由于其单次性质，HPM适用于调查在诸如生物细胞的透明结构中发生的快速现象。优选的实施例用于测量生物系统，包括对红血细胞的测量，而其量化毫秒级别的动态过程的能力可以用蒸发微米级水滴的测量来说明。

3. 发明授权

US08334982B2 Systems and methods for phase measurements 有权
标题翻译：相位测量的系统和方法
公开(公告)号：US08334982B2
公开(公告)日：2012-12-18
申请号：US12494605
申请日：2009-06-30
申请人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
发明人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
IPC分类号： G01B11/02
CPC分类号： G01B9/02091 , A61B5/14532 , A61B5/1455 , A61B5/7232 , G01B9/02002 , G01B9/02007 , G01B9/02011 , G01B9/02057 , G01B9/02063 , G01B9/02067 , G01B9/02069 , G01B9/02071 , G01B9/02072 , G01B9/02078 , G01B9/02083 , G01B9/0209 , G01B2290/45 , G01B2290/60 , G01B2290/70 , G01J9/04 , G01N21/45
摘要： Preferred embodiments of the present invention are directed to systems for phase measurement which address the problem of phase noise using combinations of a number of strategies including, but not limited to, common-path interferometry, phase referencing, active stabilization and differential measurement. Embodiment are directed to optical devices for imaging small biological objects with light. These embodiments can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering. In contrast, light based techniques with nanometer resolution enable the cellular machinery to be studied in its native state. Thus, preferred embodiments of the present invention include systems based on principles of interferometry and/or phase measurements and are used to study cellular physiology. These systems include principles of low coherence interferometry (LCI) using optical interferometers to measure phase, or light scattering spectroscopy (LSS) wherein interference within the cellular components themselves is used, or in the alternative the principles of LCI and LSS can be combined to result in systems of the present invention.
摘要翻译：本发明的优选实施例涉及用于相位测量的系统，其使用多种策略的组合来解决相位噪声问题，包括但不限于公共路径干涉测量，相位参考，主动稳定和差分测量。实施例涉及用于用光成像小生物物体的光学装置。这些实施方案可以应用于例如细胞生理学和神经科学领域。这些优选实施例基于相位测量和成像技术的原理。使用相位测量和成像技术的科学动机源于例如亚微米级别的细胞生物学，其可以包括但不限于成像发育异常起源，细胞通讯，神经元传播和遗传密码的实现。亚细胞组分的结构和动力学目前不能使用现有的方法和技术（例如x射线和中子散射）在其天然状态下研究。相比之下，具有纳米分辨率的基于光的技术使得能够以其天然状态研究细胞机械。因此，本发明的优选实施例包括基于干涉测量和/或相位测量的原理的系统，并且用于研究细胞生理学。这些系统包括使用光学干涉仪来测量相位的低相干干涉测量（LCI）原理，或使用其中使用细胞部件本身内部的干扰的光散射光谱（LSS），或者替代地，LCI和LSS的原理可以组合以产生在本发明的系统中。

4. 发明申请

US20050105097A1 Systems and methods for phase measurements 有权
公开(公告)号：US20050105097A1
公开(公告)日：2005-05-19
申请号：US10871610
申请日：2004-06-18
申请人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
发明人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
IPC分类号： G01B9/02 , G01J9/04 , G01N21/45
CPC分类号： G01B9/02091 , A61B5/14532 , A61B5/1455 , A61B5/7232 , G01B9/02002 , G01B9/02007 , G01B9/02011 , G01B9/02057 , G01B9/02063 , G01B9/02067 , G01B9/02069 , G01B9/02071 , G01B9/02072 , G01B9/02078 , G01B9/02083 , G01B9/0209 , G01B2290/45 , G01B2290/60 , G01B2290/70 , G01J9/04 , G01N21/45
摘要： Preferred embodiments of the present invention are directed to systems for phase measurement which address the problem of phase noise using combinations of a number of strategies including, but not limited to, common-path interferometry, phase referencing, active stabilization and differential measurement. Embodiment are directed to optical devices for imaging small biological objects with light. These embodiments can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering. In contrast, light based techniques with nanometer resolution enable the cellular machinery to be studied in its native state. Thus, preferred embodiments of the present invention include systems based on principles of interferometry and/or phase measurements and are used to study cellular physiology. These systems include principles of low coherence interferometry (LCI) using optical interferometers to measure phase, or light scattering spectroscopy (LSS) wherein interference within the cellular components themselves is used, or in the alternative the principles of LCI and LSS can be combined to result in systems of the present invention.

5. 发明申请

US20050057756A1 Systems and methods for phase measurements 有权
标题翻译：相位测量的系统和方法
公开(公告)号：US20050057756A1
公开(公告)日：2005-03-17
申请号：US10823389
申请日：2004-04-13
申请人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
发明人： Christopher Fang-Yen , Gabriel Popescu , Changhuei Yang , Adam Wax , Ramachandra Dasari , Michael Feld
IPC分类号： G01B9/02 , G01J9/04 , G01N21/45
CPC分类号： G01B9/02091 , A61B5/14532 , A61B5/1455 , A61B5/7232 , G01B9/02002 , G01B9/02007 , G01B9/02011 , G01B9/02057 , G01B9/02063 , G01B9/02067 , G01B9/02069 , G01B9/02071 , G01B9/02072 , G01B9/02078 , G01B9/02083 , G01B9/0209 , G01B2290/45 , G01B2290/60 , G01B2290/70 , G01J9/04 , G01N21/45
摘要： Preferred embodiments of the present invention are directed to systems for phase measurement which address the problem of phase noise using combinations of a number of strategies including, but not limited to, common-path interferometry, phase referencing, active stabilization and differential measurement. Embodiment are directed to optical devices for imaging small biological objects with light. These embodiments can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering. In contrast, light based techniques with nanometer resolution enable the cellular machinery to be studied in its native state. Thus, preferred embodiments of the present invention include systems based on principles of interferometry and/or phase measurements and are used to study cellular physiology. These systems include principles of low coherence interferometry (LCI) using optical interferometers to measure phase, or light scattering spectroscopy (LSS) wherein interference within the cellular components themselves is used, or in the alternative the principles of LCI and LSS can be combined to result in systems of the present invention.
摘要翻译：本发明的优选实施例涉及用于相位测量的系统，其使用多种策略的组合来解决相位噪声问题，包括但不限于公共路径干涉测量，相位参考，主动稳定和差分测量。实施例涉及用于用光成像小生物物体的光学装置。这些实施方案可以应用于例如细胞生理学和神经科学领域。这些优选实施例基于相位测量和成像技术的原理。使用相位测量和成像技术的科学动机源于例如亚微米级别的细胞生物学，其可以包括但不限于成像发育异常起源，细胞通讯，神经元传播和遗传密码的实现。亚细胞组分的结构和动力学目前不能使用现有的方法和技术（例如x射线和中子散射）在其天然状态下研究。相比之下，具有纳米分辨率的基于光的技术使得能够以其天然状态研究细胞机械。因此，本发明的优选实施例包括基于干涉测量和/或相位测量的原理的系统，并且用于研究细胞生理学。这些系统包括使用光学干涉仪来测量相位的低相干干涉测量（LCI）原理，或使用其中使用细胞部件本身内部的干扰的光散射光谱（LSS），或者替代地，LCI和LSS的原理可以组合以产生在本发明的系统中。

6. 发明申请

US20100249607A1 QUANTITATIVE SPECTROSCOPIC IMAGING 审中-公开
标题翻译：量化光谱成像
公开(公告)号：US20100249607A1
公开(公告)日：2010-09-30
申请号：US12568459
申请日：2009-09-28
申请人： Chung-Chieh Yu , Condon Lau , Ramachandra Dasari , Michael Feld
发明人： Chung-Chieh Yu , Condon Lau , Ramachandra Dasari , Michael Feld
IPC分类号： A61B6/00 , A61B1/06
CPC分类号： A61B5/4255 , A61B1/043 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/0088
摘要： The present invention relates to a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a powerful surveillance tool for objective early cancer detection. The design, construction, calibration, and diagnostics applications of this system is described with the use of physical tissue models. Measurements were conducted on a resected colon adenoma, and the system can be used for vivo imaging in the oral cavity.
摘要翻译：本发明涉及用于早期癌症（发育不良）的广域检测的全定量光谱成像仪。该仪器提供组织生物化学和形态学的定量图，使其成为客观早期癌症检测的强大的监测工具。使用物理组织模型描述了该系统的设计，构造，校准和诊断应用。对切除的结肠腺瘤进行测量，该系统可用于口腔中的体内成像。

7. 发明授权

US07647092B2 Systems and methods for spectroscopy of biological tissue 有权
标题翻译：生物组织光谱系统和方法
公开(公告)号：US07647092B2
公开(公告)日：2010-01-12
申请号：US10178062
申请日：2002-06-21
申请人： Jason T. Motz , Luis H. Galindo , Martin Hunter , Ramachandra Dasari , Michael S. Feld
发明人： Jason T. Motz , Luis H. Galindo , Martin Hunter , Ramachandra Dasari , Michael S. Feld
IPC分类号： A61B6/06
CPC分类号： A61B5/02007 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/0086 , A61B5/0091 , A61B5/415 , A61B5/4312 , A61B5/4519 , A61B5/7232 , G01N21/474 , G01N21/65 , G01N2021/4745 , G01N2021/4759 , G01N2021/656
摘要： The system and method of the present invention relates to using spectroscopy, for example, Raman spectroscopic methods for diagnosis of tissue conditions such as vascular disease or cancer. In accordance with a preferred embodiment of the present invention, a system for measuring tissue includes a fiber optic probe having a proximal end, a distal end, and a diameter of 2 mm or less. This small diameter allows the system to be used for the diagnosis of coronary artery disease or other small lumens or soft tissue with minimal trauma. A delivery optical fiber is included in the probe coupled at the proximal end to a light source. A filter for the delivery fibers is included at the distal end. The system includes a collection optical fiber (or fibers) in the probe that collects Raman scattered radiation from tissue, the collection optical fiber is coupled at the proximal end to a detector. A second filter is disposed at the distal end of the collection fibers. An optical lens system is disposed at the distal end of the probe including a delivery waveguide coupled to the delivery fiber, a collection waveguide coupled to the collection fiber and a lens.
摘要翻译：本发明的系统和方法涉及使用光谱学，例如用于诊断诸如血管疾病或癌症的组织条件的拉曼光谱方法。根据本发明的优选实施例，用于测量组织的系统包括具有近端，远端和2mm或更小直径的光纤探针。这种小直径允许系统用于诊断冠状动脉疾病或其他小腔或软组织，具有最小的创伤。输送光纤包括在近端耦合到光源的探针中。用于输送纤维的过滤器包括在远端。该系统包括在探针中收集来自组织的拉曼散射辐射的收集光纤（或纤维），收集光纤在近端耦合到检测器。第二过滤器设置在收集纤维的远端。光学透镜系统设置在探头的远端，包括耦合到输送纤维的输送波导，耦合到收集光纤的收集波导和透镜。

8. 发明申请

US20070167835A1 Tri modal spectroscopic imaging 审中-公开
标题翻译：三态光谱成像
公开(公告)号：US20070167835A1
公开(公告)日：2007-07-19
申请号：US11492298
申请日：2006-07-25
申请人： Chung-Chieh Yu , Condon Lau , Stephen Fulghum , Christopher Fang-Yen , Ramachandra Dasari , Michael Feld
发明人： Chung-Chieh Yu , Condon Lau , Stephen Fulghum , Christopher Fang-Yen , Ramachandra Dasari , Michael Feld
IPC分类号： A61B6/00
CPC分类号： A61B5/0059 , A61B5/0066 , G01J3/02 , G01J3/0224 , G01J3/0229 , G01J3/10 , G01J3/32 , G01N21/4738 , G01N21/49 , G01N2021/4733
摘要： The present invention relates to a spectroscopic imaging system using autofluorescence and reflectance images to diagnose tissue. A preferred embodiment of the invention uses a plurality of light sources to illuminate a tissue region to provide the fluorescence and reflectance images, respectively.
摘要翻译：本发明涉及使用自发荧光和反射图像诊断组织的光谱成像系统。本发明的优选实施例使用多个光源照射组织区域以分别提供荧光和反射图像。

9. 发明申请

US20140333929A1 3-D HOLOGRAPHIC IMAGING FLOW CYTOMETRY 审中-公开
标题翻译： 3-D全息成像流程细胞计数
公开(公告)号：US20140333929A1
公开(公告)日：2014-11-13
申请号：US14173804
申请日：2014-02-05
申请人： Yongjin Sung , Niyom Lue , Zahid Yagoob , Ramachandra Dasari , Peter T.C. So
发明人： Yongjin Sung , Niyom Lue , Zahid Yagoob , Ramachandra Dasari , Peter T.C. So
IPC分类号： G01N15/14 , G01N21/64
摘要： Refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. This feature also contains rich information that can be related to the metabolism of cells at the cellular and subcellular levels. The present invention relates to systems and methods that can provide, without any moving parts, the 3-D refractive index map of continuously flowing biological samples in a micro-fluidic channel, for example.
摘要翻译：生物标本的折射率是内在对比的来源，可以在没有光漂白或额外造影剂引起的有害影响的任何问题的情况下进行探索。该特征还包含可以与细胞和亚细胞水平的细胞代谢相关的丰富信息。本发明涉及可以提供例如在微流体通道中连续流动的生物样品的3-D折射率图的无任何移动部件的系统和方法。

10. 发明申请

US20120035442A1 PORTABLE RAMAN DIAGNOSTIC SYSTEM 有权
标题翻译：便携式拉曼诊断系统
公开(公告)号：US20120035442A1
公开(公告)日：2012-02-09
申请号：US13167445
申请日：2011-06-23
申请人： Ishan Barman , Narahara Chari Dingari , Ramachandra Dasari , Michael Feld , Chae-Ryon Kong , David Feld , Alison Hearn , Jonathan Feld
发明人： Ishan Barman , Narahara Chari Dingari , Ramachandra Dasari , Michael Feld , Chae-Ryon Kong , David Feld , Alison Hearn , Jonathan Feld
IPC分类号： A61B5/1455
CPC分类号： A61B5/14532 , A61B5/1455 , A61B5/4312 , A61B5/444 , A61B2560/0223 , G01J3/0208 , G01J3/0216 , G01J3/0218 , G01J3/0272 , G01J3/44 , G01N21/65 , G01N2201/129
摘要： The present invention further relates to the selection of the specific filter combinations, which can provide sufficient information for multivariate calibration to extract accurate analyte concentrations in complex biological systems. The present invention also describes wavelength interval selection methods that give rise to the miniaturized designs. Finally, this invention presents a plurality of wavelength selection methods and miniaturized spectroscopic apparatus designs and the necessary tools to map from one domain (wavelength selection) to the other (design parameters). Such selection of informative spectral bands has a broad scope in miniaturizing any clinical diagnostic instruments which employ Raman spectroscopy in particular and other spectroscopic techniques in general.
摘要翻译：本发明还涉及特定过滤器组合的选择，其可以提供足够的信息用于多变量校准以提取复杂生物系统中的精确分析物浓度。本发明还描述了引起小型化设计的波长间隔选择方法。最后，本发明提出了多种波长选择方法和小型化分光设备设计以及从一个域（波长选择）到另一个域（设计参数）映射的必要工具。信息谱带的这种选择在使得特别采用拉曼光谱和其他光谱技术的任何临床诊断仪器的小型化方面具有广泛的范围。

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