公开(公告)号：US20190011450A1

公开(公告)日：2019-01-10

申请号：US16123444

申请日：2018-09-06

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD. ,  SHIZUOKA PREFECTURE

Inventor： Kazuo TAKEDA ,  Namiko YAMASHITA ,  Yuu FUJIMURA ,  Kaori NISHIO ,  Yasuhiro KOH ,  Masaru WATANABE ,  Fumiaki KOIZUMI ,  Yuri UEHARA

IPC: G01N33/574 ,  G01N33/58 ,  C12N5/09

Abstract: The object of the present invention is to provide an evaluation method capable of accurately determining a metastasis of cancer, the stage of cancer progression, or the malignancy of cancer.The object can be solved by a method for detecting the degree of malignancy of each of the circulating tumor cells, characterized by the following steps: (a) bringing an epithelial cell-binding component, which specifically binds to a marker molecule expressed on epithelial cells and is fluorescently-labeled or luminescent enzyme-labeled, and a mesenchymal cell-binding component, which specifically binds to a marker molecule expressed on mesenchymal cells and is fluorescently-labeled or luminescent enzyme-labeled, into contact with a sample that possibly contains circulating tumor cells, (b) detecting a fluorescence signal or a luminescence signal of the epithelial cell-binding component and a fluorescence signal or a luminescence signal of the mesenchymal cell-binding component of each of the cells, and (c) determining the degree of epithelial-mesenchymal transition of circulating tumor cells based on the signal amount of the epithelial cell-binding component (E) and the signal amount of the mesenchymal cell-binding component (M).

公开(公告)号：US20220062905A1

公开(公告)日：2022-03-03

申请号：US17445789

申请日：2021-08-24

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA ,  Masayuki ISHIGE ,  Yuu FUJIMURA ,  Takahide INO ,  Yuji MORISHITA ,  Kosuke OSAWA ,  Soichiro TSUDA

IPC: B01L3/00 ,  G01N1/30 ,  G01N15/14

Abstract: One object of the present invention is to provide a method or apparatus for purifying target particles from high-concentration particles in a short time. The above problem can be solved by a method for purifying target particles, characterized in that the method comprises a step of sorting the target particles from a high concentration of non-target particles, wherein the sorting step is repeated for three times or more.

公开(公告)号：US20200319084A1

公开(公告)日：2020-10-08

申请号：US16904737

申请日：2020-06-18

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA

IPC: G01N15/14 ,  B01L3/00

Abstract: The object of the present invention is to provide(1) a cell sorter, (2) a flow cytometer capable of detecting sideward scattered light, (3) a method for accurately measuring cell concentration, (4) a method for multicolor staining analysis without a fluorescence correction, and the like, which satisfy requirements that carry-over and cross contamination of samples do not occur.The object can be solved by an apparatus for separating particles comprising: a flow cell wherein a flow path is formed in a flat substrate, an illumination unit configured to illuminate the particles in a sample liquid flowing through the flow path, a detection unit configured to detect particles of interest by detecting scattered light or fluorescence from the particle when the particle is illuminated, and identifying the particle based on its signal intensity, a constant-pressure pump which applies a pressure pulse to the particles in the sample liquid flowing through the flow path in the flow cell, and an electromagnetic valve connected thereto, and a control unit configured to control the movement of the electromagnetic valve based on the signal from the detection unit.

公开(公告)号：US20190078995A1

公开(公告)日：2019-03-14

申请号：US16124951

申请日：2018-09-07

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA

IPC: G01N15/14 ,  B01L3/00 ,  G01N15/10

Abstract: The object of the present invention is to provide (1) a cell sorter, (2) a flow cytometer capable of detecting sideward scattered light, (3) a method for accurately measuring cell concentration,(4) a method for multicolor staining analysis without a fluorescence correction, and the like, which satisfy requirements that carry-over and cross contamination of samples do not occur. The object can be solved by an apparatus for separating particles comprising: a flow cell wherein a flow path is formed in a flat substrate, an illumination unit configured to illuminate the particles in a sample liquid flowing through the flow path, a detection unit configured to detect particles of interest by detecting scattered light or fluorescence from the particle when the particle is illuminated, and identifying the particle based on its signal intensity, a constant-pressure pump which applies a pressure pulse to the particles in the sample liquid flowing through the flow path in the flow cell, and an electromagnetic valve connected thereto, and a control unit configured to control the movement of the electromagnetic valve based on the signal from the detection unit.

公开(公告)号：US20150140648A1

公开(公告)日：2015-05-21

申请号：US14603921

申请日：2015-01-23

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA

IPC: G01N21/64 ,  G01N33/50

CPC classification number: G01N15/1404 ,  G01N15/1427 ,  G01N15/1459 ,  G01N15/1484 ,  G01N21/53 ,  G01N21/6486 ,  G01N33/4833 ,  G01N33/5005 ,  G01N2015/1409 ,  G01N2015/149 ,  Y10T436/101666

Abstract: The present invention provides an apparatus for analyzing particles in a solution including a unit configured to place a flow cell having a flow path for flowing a sample solution containing the particles; a unit configured to illuminate the sample solution flowing through the flow path of the flow cell; a photodetector that detects a scattered light and/or fluorescence generated from the particles in the sample solution; and a unit configured to analyze the particles based on their signal intensities detected by the photodetector, wherein the flow cell has the flow path formed in a substrate, a reflection plane is formed on the side surface of the flow path, the reflection plane leads the lights generated in the flow path of the flow cell and advancing in the substrate in-plane direction to a specified region of the surface of the flow cell, and the photodetector detects the light exiting from the specified region to the outside.

Abstract translation: 本发明提供了一种用于分析溶液中的颗粒的装置，包括：单元，被配置为放置具有用于流动含有颗粒的样品溶液的流动路径的流通池; 被配置为照亮流过所述流动池的流路的样品溶液的单元; 检测从样品溶液中的颗粒产生的散射光和/或荧光的光电检测器; 以及基于由所述光检测器检测出的信号强度来分析所述粒子的单元，其中所述流通池具有形成在基板中的流路，在所述流路的侧面形成有反射面，所述反射面将所述 在流动池的流路中产生的光并且在基板的面内方向前进到流动池的表面的特定区域，并且光检测器将从指定区域射出的光检测到外部。

公开(公告)号：US20180298324A1

公开(公告)日：2018-10-18

申请号：US15573459

申请日：2016-05-12

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA ,  Yuu FUJIMURA ,  Takahide INO ,  Masayuki ISHIGE ,  Jin AKAGI

IPC: C12M1/00 ,  C12M1/34 ,  C12M1/32 ,  C12M1/26 ,  C12Q1/6881 ,  G01N15/14

Abstract: An object of the present invention is to purify and concentrate differentiating cells derived from ES cells, iPS cells, or the like without damaging them.The above problem can be solved by an apparatus for analyzing and separating particles comprising: a flow path cartridge, an illumination unit, a detection unit for detecting particles of interest, a force generating unit,wherein a sample liquid reservoir (sample reservoir) connected to a first flow path; a fourth branched flow path and a fifth branched flow path which are connected to the first flow path; a third-A reservoir connected to the fourth branched flow path; a third-B reservoir connected to the fifth branched flow path; and a fourth reservoir for reserving particles which are not sorting; are formed on the cartridge, and each reservoir comprise a means which equalizes an air pressure in the each reservoir with an air pressure of an in-device air pressure control system, and a stream of the flow path in the cartridge is controlled by controlling the air pressure in the each reservoir through the each in-device air pressure control system.

公开(公告)号：US20160146825A1

公开(公告)日：2016-05-26

申请号：US14951912

申请日：2015-11-25

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA ,  Fumie JIMMA ,  Masashi TAKAO

IPC: G01N33/574 ,  G01N15/14 ,  G01N21/64

CPC classification number: G01N33/57492 ,  G01N1/30 ,  G01N15/1436 ,  G01N15/1459 ,  G01N21/6428 ,  G01N33/54333 ,  G01N33/574 ,  G01N2015/1006 ,  G01N2015/1477 ,  G01N2021/6439 ,  G01N2201/06113 ,  G01N2333/705 ,  G01N2333/70596

Abstract: Conventional CTC detection methods have been problematic in that 1) there is no technique for automatically determining and counting live CTCs in a brief period of time, 2) no process has been developed for detecting, counting, and thereafter collecting and culturing live CTCs, and 3) there exists no flow cytometer that is contamination free and is capable of measuring an entire sample. Provided is a CTC detection method which comprises a pre-treatment step for concentrating and fluorescence staining CTCs, and a step for identifying and counting CTCs. The pre-treatment step includes attaching magnetic beads to EpCAM antibodies expressed by epithelial cell-derived CTCs and concentrating the CTCs through the use of a magnet, fluorescently labeling an epithelia cell surface marker of the CTCs through the use of EpCAM antibodies or 5E11 antibodies, and performing two types of nuclear staining, one being cell membrane-permeable and the other being cell membrane-impermeable. The identifying and counting step includes evaluating the respective absolute concentrations of live and dead CTCs in a volume of blood by automatically identifying CTCs by the ratio of a plurality of fluorescence signal intensities using a flow cytometer, and differentiating between and counting the live CTCs and the dead CTCs. In the cytometer, an entire liquid-feeding system that includes a flow cell can be replaced for each sample, and the total amount of a liquid sample can be measured.

公开(公告)号：US20160047733A1

公开(公告)日：2016-02-18

申请号：US14923654

申请日：2015-10-27

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA

IPC: G01N15/14 ,  G01N21/53 ,  G01N33/483 ,  G01N21/64

CPC classification number: G01N15/1404 ,  G01N15/1427 ,  G01N15/1459 ,  G01N15/1484 ,  G01N21/53 ,  G01N21/6486 ,  G01N33/4833 ,  G01N33/5005 ,  G01N2015/1409 ,  G01N2015/149 ,  Y10T436/101666

Abstract: The present invention provides an apparatus for analyzing particles in a solution including a unit configured to place a flow cell having a flow path for flowing a sample solution containing the particles; a unit configured to illuminate the sample solution flowing through the flow path of the flow cell; a photodetector that detects a scattered light and/or fluorescence generated from the particles in the sample solution; and a unit configured to analyze the particles based on their signal intensities detected by the photodetector, wherein the flow cell has the flow path formed in a substrate, a reflection plane is formed on the side surface of the flow path, the reflection plane leads the lights generated in the flow path of the flow cell and advancing in the substrate in-plane direction to a specified region of the surface of the flow cell, and the photodetector detects the light exiting from the specified region to the outside.

Abstract translation: 本发明提供了一种用于分析溶液中的颗粒的装置，包括：单元，被配置为放置具有用于流动含有颗粒的样品溶液的流动路径的流通池; 被配置为照亮流过所述流动池的流路的样品溶液的单元; 检测从样品溶液中的颗粒产生的散射光和/或荧光的光电检测器; 以及基于由所述光检测器检测出的信号强度来分析所述粒子的单元，其中所述流通池具有形成在基板中的流路，在所述流路的侧面形成有反射面，所述反射面将所述 在流动池的流路中产生的光并且在基板的面内方向前进到流动池的表面的特定区域，并且光检测器将从指定区域射出的光检测到外部。

公开(公告)号：US20250093253A1

公开(公告)日：2025-03-20

申请号：US18903567

申请日：2024-10-01

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA ,  Yuu FUJIMURA ,  Masayuki ISHIGE ,  Takahide INO ,  Yohsuke BANSHO ,  Jin AKAGI ,  Kosuke OSAWA

IPC: G01N15/1404 ,  B01L3/02 ,  G01N15/1433

Abstract: The object of the present invention is to provide a technique for dispensing cells as single cells. The above problem can be solved by an apparatus for dispensing particles comprising a transparent hollow pipette for dispensing sample liquid containing particles, and an image capturing means, wherein the devise has means for capturing two or more images of the dispensing liquid in the hollow pipette; means for comparing two or more shot images, distinguishing a moved particle-like substance from an unmoved particle-likesubstance in the image-captured particle-like substances, and identifying the moved particle-like substance as a suspended particle; and means for dispensing a sample liquid containing a target number of suspended particles.

公开(公告)号：US20240402068A1

公开(公告)日：2024-12-05

申请号：US18800554

申请日：2024-08-12

Applicant: ON-CHIP BIOTECHNOLOGIES CO., LTD.

Inventor： Kazuo TAKEDA

IPC: G01N15/1434 ,  B01L3/00 ,  G01N15/10 ,  G01N15/14 ,  G01N15/149

Abstract: The object of the present invention is to provide (1) a cell sorter, (2) a flow cytometer capable of detecting sideward scattered light, (3) a method for accurately measuring cell concentration, (4) a method for multicolor staining analysis without a fluorescence correction, and the like, which satisfy requirements that carry-over and cross contamination of samples do not occur. The object can be solved by an apparatus for separating particles comprising: a flow cell wherein a flow path is formed in a flat substrate, an illumination unit configured to illuminate the particles in a sample liquid flowing through the flow path, a detection unit configured to detect particles of interest by detecting scattered light or fluorescence from the particle when the particle is illuminated, and identifying the particle based on its signal intensity, a constant-pressure pump which applies a pressure pulse to the particles in the sample liquid flowing through the flow path in the flow cell, and an electromagnetic valve connected thereto, and a control unit configured to control the movement of the electromagnetic valve based on the signal from the detection unit.