公开(公告)号：US20130228706A1

公开(公告)日：2013-09-05

申请号：US13864867

申请日：2013-04-17

Applicant: OLYMPUS CORPORATION

Inventor： Mitsushiro Yamaguchi ,  Tetsuya Tanabe

IPC: G01N21/64

CPC classification number: G01N21/6445 ,  G01N15/1434 ,  G01N15/1456 ,  G01N21/6408 ,  G01N21/6458 ,  G02B21/0068 ,  G02B21/0076 ,  G02B21/0092

Abstract: There is provided an optical analysis technique which observes a polarization characteristic of a light-emitting particle using the scanning molecule counting method using an optical measurement with a confocal microscope or a multiphoton microscope. In the inventive optical analysis technique, the light detection region is irradiated with excitation light consisting of predetermined polarized light component(s) and the intensity of at least one polarized light component of the light from the light detection region is detected with moving the position of the light detection region of the optical system in a sample solution; a signal of each light-emitting particle is detected individually in the intensity of at least one polarized light component; and based on the intensity of at least one polarized light component of the signal of the detected light-emitting particle, the polarization characteristic value of the light-emitting particle is computed.

Abstract translation: 提供了一种光学分析技术，其使用通过共聚焦显微镜或多光子显微镜的光学测量的扫描分子计数方法观察发光粒子的偏振特性。 在本发明的光学分析技术中，用由预定偏振光分量组成的激发光照射光检测区域，并且通过移动光检测区域的位置来检测来自光检测区域的光的至少一个偏振光分量的强度 样品溶液中的光学系统的光检测区域; 以至少一个偏振光分量的强度分别检测每个发光粒子的信号; 并且基于检测到的发光粒子的信号的至少一个偏振光分量的强度，计算发光粒子的偏振特性值。

公开(公告)号：US20130122488A1

公开(公告)日：2013-05-16

申请号：US13746968

申请日：2013-01-22

Applicant: OLYMPUS CORPORATION

Inventor： Tetsuya Tanabe ,  Hidetaka Nakata ,  Takuya Hanashi ,  Kunio Hori ,  Kazutaka Nishikawa

IPC: G01N33/53 ,  C12Q1/68

CPC classification number: G01N33/5308 ,  C12Q1/6818 ,  G01N5/045 ,  G01N15/1456 ,  G01N21/6458 ,  G01N2015/1486 ,  G02B21/0048 ,  G02B21/0076

Abstract: There is provided an optical analysis technique enabling the detection of the condition or characteristic of a particle to be observed contained at a low concentration or number density in a sample solution using a light-emitting probe. The inventive optical analysis technique uses an optical system capable of detecting light from a micro region in a solution, such as an optical system of a confocal microscope or a multiphoton microscope, to detect the light from the light-emitting probe having bound to a particle to be observed while moving the position of the micro region in the sample solution (while scanning the inside of the sample solution with the micro region), thereby detecting individually the particle crossing the inside of the micro region to enable the counting of the particle(s) or the acquisition of the information on the concentration or number density of the particle.

Abstract translation: 提供了一种光学分析技术，其能够使用发光探针检测在样品溶液中以低浓度或数量密度包含的待观察颗粒的状态或特性。 本发明的光学分析技术使用能够检测来自诸如共焦显微镜或多光子显微镜的光学系统的解决方案中的微区域的光的光学系统，以检测来自发光探针的光，其结合到颗粒 在移动样品溶液中的微区域的位置（同时用微区域扫描样品溶液的内部）的同时观察，从而单独检测与微区域内部交叉的粒子，以使得能够计数颗粒（ s）或获取关于颗粒的浓度或数量密度的信息。

公开(公告)号：US11119022B2

公开(公告)日：2021-09-14

申请号：US16584853

申请日：2019-09-26

Applicant: OLYMPUS CORPORATION

Inventor： Mitsushiro Yamaguchi ,  Tetsuya Tanabe

IPC: G01N15/06 ,  G01N15/14 ,  G02B26/08 ,  G02B26/10

Abstract: An optical analysis device includes a light source, a beam shaping unit, a relative movement unit, a photodetector, and a position detector. The light source unit generates a light beam. The beam shaping unit forms a flat beam portion. The relative movement unit is configured to cause the flat beam portion and a test sample including marker particles to relatively move in a minor axis direction of the flat beam portion. The photodetector is configured to detect a light intensity and a light emitting position in a plane orthogonal to the minor axis direction. The position detector is capable of detecting spatial positions of the marker particles on the basis of information on a relative movement amount of the flat beam portion, information on the light intensity and the light emitting position, and a change of the light intensity generated according to a relative movement of the flat beam portion.

公开(公告)号：US20190271027A1

公开(公告)日：2019-09-05

申请号：US16382532

申请日：2019-04-12

Applicant: OLYMPUS CORPORATION ,  RIKEN

Inventor： Takuya Hanashi ,  Tetsuya Tanabe ,  Takeshi Hanami ,  Yoshihide Hayashizaki

IPC: C12Q1/6818 ,  C12Q1/6876 ,  G01N21/64

Abstract: A method for detecting a target nucleic acid molecule of the present invention includes a step of associating a first and third probes labeled with a first fluorescent substance which is an energy donor with a second probe labeled with a second fluorescent substance which is an energy acceptor to form an associate in a nucleic acid molecule; and a step of emitting light with an excitation wavelength of the first fluorescent substance to the associate to detect the target nucleic acid molecule using fluorescence released from the second fluorescent substance in the associate as an indicator, wherein a region associating with the second probe is between a region associating with the first probe and a region associating with the third probe in the target nucleic acid molecule.

公开(公告)号：US10371631B2

公开(公告)日：2019-08-06

申请号：US14188375

申请日：2014-02-24

Applicant: OLYMPUS CORPORATION

Inventor： Tetsuya Tanabe ,  Mitsushiro Yamaguchi

IPC: G01N21/64 ,  G02B21/00

Abstract: There is provided an optical analysis technique of detecting light of a light-emitting particle in a sample solution in the scanning molecule counting method using the light measurement with a confocal or multiphoton microscope, for suppressing the scattering in detected results of signals of light of light-emitting particles smaller and achieving the improvement of accuracy. The inventive technique comprises moving the position of a light detection region along a predetermined route for multiple circulation times by changing the optical path of the optical system; detecting light from the light detection region and generating time series light intensity data during the moving of the light detection region and detecting individually a signal indicating light from each light-emitting particle existing in the predetermined route using the time series light intensity data obtained in the circulating movements of the light detection region of multiple times.

公开(公告)号：US09739698B2

公开(公告)日：2017-08-22

申请号：US15084246

申请日：2016-03-29

Applicant: OLYMPUS CORPORATION

Inventor： Tetsuya Tanabe ,  Seiji Kondo

IPC: G01N15/06 ,  G02B21/16 ,  G02B21/00 ,  G01N21/64 ,  G01N15/00

CPC classification number: G01N15/06 ,  G01N21/64 ,  G01N2015/0065 ,  G01N2015/0687 ,  G01N2015/0693 ,  G02B21/0032 ,  G02B21/0048 ,  G02B21/008 ,  G02B21/0084 ,  G02B21/16 ,  G02B2207/114

Abstract: In the scanning molecule counting method using optical measurement with a confocal or multiphoton microscope, there is provided a technique of computing a light-emitting particle concentration which changes with time and detecting a concentration change velocity or a reaction velocity. The inventive optical analysis technique of detecting light of light-emitting particles in a sample solution generates time series light intensity data of light from a light detection region detected with moving the position of the light detection region of the microscope in the sample solution; measures successively an interval of generation times of signals of the light-emitting particles detected in the time series light intensity data; and determines the concentration or concentration change velocity of the light-emitting particles, using the successively measured signal generation time intervals.

公开(公告)号：US09435727B2

公开(公告)日：2016-09-06

申请号：US13969830

申请日：2013-08-19

Applicant: OLYMPUS CORPORATION

Inventor： Takuya Hanashi ,  Mitsushiro Yamaguchi ,  Tetsuya Tanabe

IPC: G01N15/14 ,  G01N21/64 ,  G01N21/51 ,  G02B21/00

CPC classification number: G01N15/1429 ,  G01N21/51 ,  G01N21/6408 ,  G01N21/645 ,  G01N21/6458 ,  G02B21/0076 ,  G02B21/0084

Abstract: There is provided a structure to make the setting of a criterion for eliminating noises easy in the scanning molecule counting method. In the inventive optical analysis technique of detecting light of a light-emitting particle in a sample solution, time series light intensity data of light from a light detection region detected with moving the position of the light detection region in the sample solution is generated, and a signal of a light-emitting particle individually is detected in the time series light intensity data, wherein a signal having a light intensity in a light intensity range set based upon a signal generation frequency integrated value distribution which is a distribution, obtained by using as a variable an intensity of a signal, of integrated values of generation frequencies of signals having an intensity not lower than the variable is extracted as the signal of the light-emitting particle.

Abstract translation: 提供了一种结构，用于设置扫描分子计数方法中消除噪声的标准。 在本发明的用于检测样品溶液中的发光粒子的光的光学分析技术中，产生了通过移动样品溶液中的光检测区域的位置而检测到的光检测区域的光的时间序列光强度数据， 在时间序列光强度数据中检测出发光粒子的信号，其中，根据作为分配获得的作为分布的信号生成频率积分值分布设定的光强度的光强度的信号， 提取具有不低于该变量的信号的信号的产生频率的积分值的信号强度的变量作为发光粒子的信号。

公开(公告)号：US20160252456A1

公开(公告)日：2016-09-01

申请号：US15151524

申请日：2016-05-11

Applicant: OLYMPUS CORPORATION

Inventor： Takuya Hanashi ,  Tetsuya Tanabe

IPC: G01N21/64

CPC classification number: G01N21/64 ,  G01N15/14 ,  G01N15/1429 ,  G01N15/1434 ,  G01N21/51 ,  G01N21/6408 ,  G01N21/645 ,  G01N21/6452 ,  G01N21/6458 ,  G02B21/0032 ,  G02B21/0076 ,  G02B21/008

Abstract: There is provided a single particle detection technique based on a scanning molecule counting method, enabling individual detection of a single particle using light measurement with a confocal or multiphoton microscope, and quantitative observation of conditions or characteristics of the particle. The inventive technique of detecting a single particle in a sample solution detects light containing substantially constant background light from a light detection region with moving the position of the light detection region of the microscope in a sample solution to generate time series light intensity data; and detects individually a light intensity reduction occurred when a single particle which does not emit light (or a particle whose emitting light intensity in a detected wavelength band is lower than the background light) enters in the light detection region in the time series light intensity data as a signal indicating the existence of each single particle.

Abstract translation: 提供了基于扫描分子计数方法的单粒子检测技术，能够使用共聚焦或多光子显微镜进行光测量来单个检测单个颗粒，并定量观察颗粒的条件或特性。 本发明的检测样品溶液中的单个颗粒的技术通过在样品溶液中移动显微镜的光检测区域的位置来检测来自光检测区域的基本上恒定的背景光的光，以产生时间序列光强度数据; 并且单独检测当不发光的单个颗粒（或检测波长带中的发光强度低于背景光的颗粒）在时间序列光强数据中的光检测区域中时发生的光强度降低 作为指示每个单个颗粒的存在的信号。

公开(公告)号：US20160209315A1

公开(公告)日：2016-07-21

申请号：US15084246

申请日：2016-03-29

Applicant: OLYMPUS CORPORATION

Inventor： Tetsuya Tanabe ,  Seiji Kondo

IPC: G01N15/06 ,  G02B21/16 ,  G02B21/00

CPC classification number: G01N15/06 ,  G01N21/64 ,  G01N2015/0065 ,  G01N2015/0687 ,  G01N2015/0693 ,  G02B21/0032 ,  G02B21/0048 ,  G02B21/008 ,  G02B21/0084 ,  G02B21/16 ,  G02B2207/114

Abstract: In the scanning molecule counting method using optical measurement with a confocal or multiphoton microscope, there is provided a technique of computing a light-emitting particle concentration which changes with time and detecting a concentration change velocity or a reaction velocity. The inventive optical analysis technique of detecting light of light-emitting particles in a sample solution generates time series light intensity data of light from a light detection region detected with moving the position of the light detection region of the microscope in the sample solution; measures successively an interval of generation times of signals of the light-emitting particles detected in the time series light intensity data; and determines the concentration or concentration change velocity of the light-emitting particles, using the successively measured signal generation time intervals.

Abstract translation: 在使用共焦或多光子显微镜的光学测量的扫描分子计数方法中，提供了计算随时间变化并检测浓度变化速度或反应速度的发光粒子浓度的技术。 本发明的检测样品溶液中的发光粒子的光的光学分析技术，通过在样品溶液中移动显微镜的光检测区域的位置，检测出来的光检测区域的光的时间序列的光强度数据; 连续地测量在时间序列光强数据中检测到的发光粒子的信号的产生次数的间隔; 并且使用连续测量的信号产生时间间隔来确定发光粒子的浓度或浓度变化速度。

公开(公告)号：US20130242307A1

公开(公告)日：2013-09-19

申请号：US13888868

申请日：2013-05-07

Applicant: OLYMPUS CORPORATION

Inventor： Takuya Hanashi ,  Tetsuya Tanabe ,  Mitsushiro Yamaguchi

IPC: G01J1/16

CPC classification number: G01J1/16 ,  G01C21/02 ,  G01J1/58 ,  G01N15/1463 ,  G01N21/6452 ,  G01N21/6458 ,  G01N2021/6421 ,  G02B21/0032 ,  G02B21/0076 ,  G02B21/26

Abstract: The inventive technique of detecting and analyzing light from a light-emitting particle in accordance with the scanning molecule counting method using an optical measurement with a confocal microscope or a multiphoton microscope is characterized by detecting intensities of components of two or more wavelength bands of light from a light detection region of an optical system with moving the position of the light detection region in a sample solution by changing the optical path of the optical system of the microscope; detecting individually signals of the light from each light-emitting particle in the intensities of the components of the two or more wavelength bands of the detected light; and identifying a kind of light-emitting particle based on the intensities of the components of the two or more wavelength bands of the signals of the light of the detected light-emitting particle.

Abstract translation: 根据使用共聚焦显微镜或多光子显微镜的光学测量的扫描分子计数法检测和分析来自发光粒子的光的本发明的技术的特征在于检测两个或更多个波长带的光的分量的强度， 光学系统的光检测区域，通过改变显微镜的光学系统的光路来移动样品溶液中的光检测区域的位置; 在检测到的光的两个或更多个波长带的分量的强度中单独地检测来自每个发光粒子的光的信号; 并且基于检测到的发光粒子的光的信号的两个或更多波长带的分量的强度来识别发光粒子的种类。