公开(公告)号：US10451402B2

公开(公告)日：2019-10-22

申请号：US13358254

申请日：2012-01-25

Applicant: Zahid Yaqoob ,  Wonshik Choi ,  Toyohiko Yamauchi ,  Michael Feld ,  David Feld ,  Alison Hearn ,  Jonathan Feld

Inventor： Zahid Yaqoob ,  Wonshik Choi ,  Toyohiko Yamauchi ,  Michael Feld

IPC: G01B9/04 ,  G01N21/45 ,  G01B9/02 ,  G02B27/10 ,  G02B27/50 ,  G03H1/04 ,  G03H1/00

Abstract: The present invention relates to a full-field reflection phase microscope. In a preferred embodiment, the invention can combine low-coherence interferometry and off-axis digital holographic microscopy (DHM). The reflection-based DHM provides highly sensitive and a single-shot imaging of cellular dynamics while the use of low coherence source provides a depth-selective measurement. A preferred embodiment of the system uses a diffraction grating in the reference arm to generate an interference image of uniform contrast over the entire field-of-view albeit low-coherence light source. With improved path-length sensitivity, the present invention is suitable for full-field measurement of membrane dynamics in live cells with sub-nanometer-scale sensitivity.

公开(公告)号：US20150177133A1

公开(公告)日：2015-06-25

申请号：US14490242

申请日：2014-09-18

Applicant: Alison Hearn ,  David Feld ,  Jonathan Feld

Inventor： Wonshik Choi ,  Ramachandra Dasari ,  Christopher Fang-Yen ,  Michael Feld

IPC: G01N21/45 ,  G01N21/64

CPC classification number: G01N21/45 ,  G01N21/51 ,  G01N21/6458 ,  G01N21/6486 ,  G01N2021/458 ,  G01N2201/061 ,  G01N2201/105 ,  G01N2201/12

Abstract: The present invention relates to systems and methods for quantitative three-dimensional mapping of refractive index in living or non-living cells, tissues, or organisms using a phase-shifting laser interferometric microscope with variable illumination angle. A preferred embodiment provides tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure and the quantitative characterization of specimen-induced aberrations in high-resolution microscopy with multiple applications in tissue light scattering.

Abstract translation: 本发明涉及使用具有可变照明角度的移相激光干涉显微镜在生活或非活细胞，组织或生物体中定量三维映射折射率的系统和方法。 优选的实施方案提供细胞和多细胞生物的层析成像，以及在组织光散射中具有多种应用的高分辨率显微镜中细胞结构的时间依赖性变化和样品诱导的像差的定量表征。

公开(公告)号：US20130265585A1

公开(公告)日：2013-10-10

申请号：US13715475

申请日：2012-12-14

Applicant: David Feld ,  Jonathan Feld ,  Alison Hearn

Inventor： Christopher Fang-Yen ,  Gabriel Popescu ,  Changhuei Yang ,  Adam Wax ,  Ramachandra Dasari ,  Michael Feld

IPC: G01B9/02

CPC classification number: 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

Abstract: Preferred embodiments of the present invention are directed to systems for phase measurement such as 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. 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.

Abstract translation: 本发明的优选实施例涉及用于相位测量的系统，例如用于利用光成像小生物物体。 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。 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。

公开(公告)号：US20120307035A1

公开(公告)日：2012-12-06

申请号：US13358254

申请日：2012-01-25

Applicant: Zahid Yaqoob ,  Wonshik Choi ,  Toyohiko Yamauchi ,  Michael Feld ,  David Feld ,  Alison Hearn ,  Jonathan Feld

Inventor： Zahid Yaqoob ,  Wonshik Choi ,  Toyohiko Yamauchi ,  Michael Feld ,  David Feld ,  Alison Hearn ,  Jonathan Feld

IPC: H04N7/18

CPC classification number: G01B9/04 ,  G01B9/02032 ,  G01B9/02047 ,  G01B9/02064 ,  G01B9/0207 ,  G01B9/02084 ,  G01B9/02091 ,  G01N21/45 ,  G02B27/1086 ,  G02B27/50 ,  G03H1/0443 ,  G03H2001/005 ,  G03H2001/0456 ,  G03H2001/0467 ,  G03H2222/24

Abstract: The present invention relates to a full-field reflection phase microscope. In a preferred embodiment, the invention can combine low-coherence interferometry and off-axis digital holographic microscopy (DHM). The reflection-based DHM provides highly sensitive and a single-shot imaging of cellular dynamics while the use of low coherence source provides a depth-selective measurement. A preferred embodiment of the system uses a diffraction grating in the reference arm to generate an interference image of uniform contrast over the entire field-of-view albeit low-coherence light source. With improved path-length sensitivity, the present invention is suitable for full-field measurement of membrane dynamics in live cells with sub-nanometer-scale sensitivity.

Abstract translation: 本发明涉及全场反射相位显微镜。 在优选实施例中，本发明可以组合低相干干涉测量和离轴数字全息显微镜（DHM）。 基于反射的DHM提供高灵敏度和单次成像的细胞动力学，而使用低相干源提供深度选择性测量。 该系统的优选实施例使用参考臂中的衍射光栅来产生在整个视场内虽然具有低相干光源的均匀对比度的干涉图像。 随着路径长度灵敏度的提高，本发明适用于具有亚纳米级灵敏度的活细胞膜动力学的全场测量。